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Background Most breast cancers (BCs) in men are hormone receptor-positive. Adjuvant tamoxifen is part of the standard treatment of these patients. Small, single-institution studies have suggested that men have high rates of discontinuing adjuvant endocrine treatment. The authors examined rates of tamoxifen discontinuation and medication adherence in a large population-based cohort of male patients with BC. Methods In the Surveillance, Epidemiology, and End Results-Medicare database, male patients with invasive nonmetastatic BC, diagnosed between 2007 and 2013, who were ≥65 years old, had Part D coverage, and had tamoxifen prescriptions within 1 year of diagnosis were identified. Adherence was defined as a medication possession ratio of ≥80% among those patients who were filling tamoxifen prescriptions. Logistic regression model was used to assess predictors of tamoxifen adherence. Results A total of 451 patients met eligibility criteria. The median age at diagnosis was 75 years. The median follow-up was 32.5 months. The rates of tamoxifen discontinuation were 15.8%, 24.3%, 31.3%, 36.9%, and 48.3% at 1, 2, 3, 4, and 5 years after diagnosis, respectively. Among the men who were still taking tamoxifen, the corresponding adherence rates were 76.9%, 73.6%, 68.7%, 64.8%, and 60.2%. In the adjusted model, significant predictors of lower adherence included residing in a high poverty area (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.28-2.12) and a Charlson comorbidity score of ≥2 (OR, 0.46; 95% CI, 0.22-0.97). Conclusion Older men with breast cancer have high rates of tamoxifen discontinuation, with 48% of all patients discontinuing tamoxifen before the end of year 5. Additionally, even among those patients continuing tamoxifen, a substantial number of patients are nonadherent. Further research should evaluate potentially modifiable reasons for treatment discontinuation and lack of adherence to tamoxifen.

Non-Hispanic black (NHB) women and those of lower socioeconomic status (SES) have inferior breast cancer outcomes compared with non-Hispanic white (NHW) women and those of higher SES. We examined racial and SES disparities in breast cancer survival within the AJCC 8th edition pathologic prognostic staging system. Using the Surveillance, Epidemiology and End Results Program, we identified patients diagnosed with invasive breast cancer from 2010 to 2015, with follow-up through 2016. Census tract-level SES (cSES) data were available as a composite index and analyzed in quintiles. Cox proportional-hazards survival analyses adjusted for age, race, cSES, insurance, marital status, histology, pathologic prognostic stage, and treatment were used to estimate disease-specific survival (DSS). A total of 259,852 patients were included: 176,369 (67.9%) NHW; 28,510 (11.0%) NHB; 29,737 (11.4%) Hispanic; and 22,887 (8.8%) Asian. NHB race and lower cSES were associated with increased incidence of triple-negative disease compared with NHW (p

BACKGROUND: Tamoxifen and aromatase inhibitors (AIs) are used as adjuvant hormonal therapy (AHT) for early-stage hormone receptor–positive (HR+) breast cancer. Treatment for 5 years reduces cancer mortality by 30%. Despite this benefit, adherence to AHT has been suboptimal. Here, we evaluated AHT initiation and patient adherence in women with private health insurance. MATERIALS AND METHODS: Female patients with breast cancer ≥ 18 years of age who underwent mastectomy or lumpectomy between 1999 and 2015 were identified in the IBM MarketScan Research Database. AHT initiation and adherence rates were estimated for all AHT users regardless of HR+ status. Initiation rates were standardized using HR+ breast cancer incidence rates in the Surveillance, Epidemiology, and End Results (SEER) program. Adherence was defined as medication possession ratio ≥ 80%. Risk ratios, odds ratios, and their 95% CIs were calculated for factors associated with patients' initiation and adherence. RESULTS: Among 80,224 patients, the raw initiation rate was 71.8% and the standardized rate was 87.5%. We found 61.2% patients initiated treatment with AIs and 38.8% with tamoxifen. Patients' 1-year adherence rate was 84.4% and the 5-year rate was 65.2%. Prescription by mail-in order, using a single AHT regimen, 50 to 69 years of age, monthly out-of-pocket drug payment ≤ $11, in US dollars, no depression, no comorbidity, living in the Northeast, treatment in recent years, and receipt of a combination of chemotherapy, radiation, and surgery were associated with better adherence. CONCLUSION: Five-year AHT adherence rates are low among female patients with breast cancer with private health insurance. Effective approaches to improve AHT adherence are needed.

Background: Triple negative breast cancer (TNBC) disproportionally impacts Black and Hispanic women and is suggested to be partly responsible for disparities observed in breast cancer mortality. We sought to evaluate the impact of race/ethnicity on TNBC molecular subtype, immune profile, pathologic complete response (pCR) and recurrence free survival (RFS). Methods: The ARTEMIS trial (NCT02276443) uses imaging response and molecular profiling to personalize neoadjuvant chemotherapy in early stage TNBC. After 4 cycles of AC, patients with chemo-sensitive disease receive standard taxane-based therapy, while those with chemo-resistant disease are offered therapeutic trials based upon molecular profiling. Pathologic response was assessed at surgery. Patients self-reported race/ethnicity was categorized as Asian, Black/African-American, Hispanic/Latino and White (non-Hispanic). Patients were excluded if no race or ethnicity was reported. Clinical and pathologic factors were recorded and compared. Gene expression profiling was performed by RNAseq to determine Vanderbilt signature. PD-L1 and Androgen Receptor (AR) were determined by immunohistochemistry. Frequencies at which various factors were observed by race/ethnicity were calculated and Fisher’s exact test performed to determine statistical significance. Kaplan-Meier analysis was used to estimate survival stratified by pCR status and race/ethnicity. Results: Among 321 women enrolled in ARTEMIS, 26 (8.1%) were classified as Asian, 50 (15.6%) as Black, 59 (18.4%) as Hispanic and 186 (57.9%) as White. Demographic and clinical features were similar, except Black women were more likely to have BMI ≥30 (70.0%, p Conclusion: Among this population of patients with TNBC treated with neoadjuvant chemotherapy there was no statistically significant difference observed in TNBC Vanderbilt signature, PD-L1 staining, sTIL, pCR or RFS by race/ethnicity. Asian women were found to have a higher incidence of AR-positive subtype. Numerically higher rates of N3 stage in Black women and RCB-III classification in Black and Hispanic women were identified, however not statistically significant. Larger cohorts of patients are needed to further investigate these findings. Table 1. TNBC profiling compared by race/ethnicity.Total n (%)Asian n (%)Black n (%)Hispanic/Latino n (%)White n (%)p valueVanderbilt signature n (%) Basal like (BL1) Basal like 2 (BL2) Immunomodulatory (IM) Luminal androgen receptor (LAR) Mesenchymal (M) Mesenchymal stem-like (MSL) Unstable (UNS)231 50 (21.6) 25 (10.8) 42 (18.2) 22 (9.5) 48 (20.8) 14 (6.0) 30 (13.0)21 (9.1) 0 (0.0) 4 (19.0) 5 (23.8) 3 (14.3) 5 (23.8) 1 (4.8) 3 (14.3)35 (15.2) 9 (25.7) 5 (14.3) 6 (17.1) 2 (5.7) 7 (20.0) 1 (2.9) 5 (14.3)43 (18.6) 14 (32.5) 3 (7.0) 10 (23.2) 5 (11.6) 6 (14.0) 2 (4.7) 3 (7.0)132 (57.1) 27 (20.5) 13 (9.8) 21 (15.9) 12 (9.1) 30 (22.7) 10 (7.6) 19 (14.4)NSAndrogen Receptor n (%) Positive (>=10%) Negative (1298 212 (71.1) 86 (28.9)24 (8.1) 15 (62.5) 9 (37.5)47 (15.8) 33 (70.2) 14 (29.8)57 (19.1) 40 (70.2) 17 (29.8)170 (57.0) 124 (72.9) 46 (27.1)NSStromal tumor infiltrating lymphocytes (sTIL) n (%) High (>=20%) Low ( Citation Format: Mediget Teshome, Ryan Sun, Elizabeth E. Ravenberg, Abenaa Brewster, Mariana Chavez-MacGregor, Jason B. White, Stacy Moulder. Impact of race/ethnicity on triple negative breast cancer molecular features, treatment response and clinical outcomes in patients receiving neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-12.

Purpose: Report results of the phase Ib dose-escalation/expansion study of triplet therapy with cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor (ribociclib), mTOR inhibitor (everolimus), and endocrine therapy (exemestane). Patients and Methods: Postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), pretreated, advanced breast cancer (ABC) were enrolled. The primary objective of the dose-escalation phase was to estimate the MTD and recommended phase II dose (RP2D) of triplet therapy through evaluation of the incidence of dose-limiting toxicities. Safety, tolerability, and efficacy of the RP2D were evaluated in the dose-expansion phase in patients naïve or refractory to CDK4/6 inhibitor therapy. Results: Patients (N = 116) received triplet therapy (n = 83 in the dose-escalation phase; n = 33 in the dose-expansion phase). A dose-dependent drug–drug interaction was observed for everolimus, with exposure increasing two- to fourfold in the presence of ribociclib. The RP2D was determined to be ribociclib 300 mg once daily, 3 weeks on/1 week off in a 4-week cycle, plus everolimus 2.5 mg once daily, plus exemestane 25 mg once daily taken with food. The safety profile was consistent with the known profiles of the combination partners, and preliminary evidence of antitumor activity was observed. Higher ESR1 gene expression trended with better treatment response to triplet therapy; higher gene expression of MAPK pathway genes trended with worse treatment response. Conclusions: Triplet therapy with endocrine therapy and mTOR and CDK4/6 inhibition provides clinical benefit and an acceptable safety profile in previously treated postmenopausal women with HR+, HER2− ABC.

Lessons Learned The combination of eribulin with 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) was not superior to the combination of paclitaxel with FAC/FEC and was associated with greater hematologic toxicity. Eribulin followed by an anthracycline-based regimen is not recommended as a standard neoadjuvant therapy in nonmetastatic operable breast cancer. Background Neoadjuvant systemic therapy is the standard of care for locally advanced operable breast cancer. We hypothesized eribulin may improve the pathological complete response (pCR) rate compared with paclitaxel. Methods We conducted a 1:1 randomized open-label phase II study comparing eribulin versus paclitaxel followed by 5-fluorouracil, either doxorubicin or epirubicin, and cyclophosphamide (FAC/FEC) in patients with operable HER2-negative breast cancer. pCR and toxicity of paclitaxel 80 mg/m2 weekly for 12 doses or eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle for 4 cycles followed by FAC/FEC were compared. Results At the interim futility analysis, in March 2015, 51 patients (28 paclitaxel, 23 eribulin) had received at least one dose of the study drug and were thus evaluable for toxicity; of these, 47 (26 paclitaxel, 21 eribulin) had undergone surgery and were thus evaluable for efficacy. Seven of 26 (27%) in the paclitaxel group and 1 of 21 (5%) in the eribulin group achieved a pCR, and this result crossed a futility stopping boundary. In the paclitaxel group, the most common serious adverse events (SAEs) were neutropenic fever (grade 3, 3 patients, 11%). In the eribulin group, nine patients (39%) had neutropenia-related SAEs, and one died of neutropenic sepsis. The study was thus discontinued. For the paclitaxel and eribulin groups, the 5-year event-free survival (EFS) rates were 81.8% and 74.0% (hazard ratio [HR], 1.549; 95% confidence interval [CI], 0.817–2.938; p = .3767), and the 5-year overall survival (OS) rates were 100% and 84.4% (HR, 5.813; 95% CI, 0.647–52.208; p = .0752), respectively. Conclusion We did not observe a higher proportion of patients undergoing breast conservation surgery in the eribulin group than in the paclitaxel group. The patients treated with eribulin were more likely to undergo mastectomy and less likely to undergo breast conservation surgery, but the difference was not statistically significant. As neoadjuvant therapy for operable HER2-negative breast cancer, eribulin followed by FAC/FEC is not superior to paclitaxel followed by FAC/FEC and is associated with a higher incidence of neutropenia-related serious adverse events.

Background Bisphosphonates and denosumab, as adjuvant therapy in breast cancer, have been associated in some studies with improved cancer outcomes. The potential benefits of these drugs used at the lower doses commonly given for osteoporosis have not been established. The objective of this study was to investigate the association between therapy with bone-modifying agents (BMAs) and survival in older women with early breast cancer. Methods The authors conducted a retrospective cohort study of women aged ≥66 years with breast cancer who were included in the Surveillance, Epidemiology, and End Results and Texas Cancer Registry Medicare-linked databases. Associations were examined between the receipt of BMAs at dosages indicated for osteoporosis within 2 years after diagnosis and overall and breast cancer-specific survival. Cox proportional hazards models and propensity score adjustment and matching were used for the analyses. Results Of the 37,724 women included, 7925 (21%) received at least 6 months of a BMA within the first 2 years of breast cancer diagnosis, including bisphosphonates only in 6898 women (80.7%), denosumab only in 1204 (15.2%), and both classes of BMAs in 323 (4.1%). The median follow-up was 64 months. The receipt of a bisphosphonate was associated with improved overall survival (hazard ratio [HR], 0.87; 95% CI, 0.82-0.93) and breast cancer-specific survival (HR, 0.77; 95% CI, 0.64-0.92) after multivariable adjustment. Benefits were primarily seen for patients who had stage II and III disease. No benefits were observed with denosumab (stage II: HR, 1.05 [95% CI, 0.90-1.22]; stage III: HR, 1.09 [95% CI, 0.66-1.82]). Conclusions Bisphosphonates at the doses recommended for osteoporosis are associated with improved survival in older postmenopausal women with early breast cancer.

Background There is limited literature on patterns of everolimus use and subsequent hospitalizations and emergency room (ER) visits in real-world clinical practice. In this study, we describe patterns of everolimus use and hospitalizations and ER visits in a large cohort of patients with breast cancer (BC). Materials and Methods Patients with BC treated with everolimus were identified in the MarketScan database from 2009 to 2016. The pattern of everolimus use and frequency of associated ER visits and hospitalizations during treatment (between the first claim and 30 days after the last claim for everolimus) were identified. Descriptive statistics and regression models were used. Results A total of 3,556 everolimus users were identified (median age of 60 years; median days of use, 112). The initial prescribed dose was 10 mg in 74.8% of the patients. Compared with the initial dose, 23.5% of patients had a dose change. Forty-six percent of patients were hospitalized or had an ER visit during the treatment with everolimus. Age greater than 71, higher comorbidity score, treatment year prior to 2012, and lower initial dose were found to be significantly associated with ER visit/hospitalization in the regression models. Conclusions A significant proportion of patients receiving everolimus had an ER visit or hospitalization during the use of everolimus. These results provide data regarding risks and benefits of treatment with everolimus. These results will be helpful in identifying patients at higher risk of hospitalizations or ER visits and facilitate evidence-based decision making to avoid serious complications. Implications for Practice Everolimus, a mammalian target of rapamycin inhibitor, is approved in combination with exemestane in patients with hormone receptor–positive tumors previously treated with anastrozole or letrozole. As new drugs become available, it is crucial to understand the adverse events and potential complications associated with the use of such drugs in the general population, outside of the controlled clinical trial setting. This study describes the patterns of everolimus use and adverse events, including hospitalization and emergency room visits, in a large cohort of patients with metastatic breast cancer in routine practice.

BACKGROUND The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm). METHODS The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis. RESULTS Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age

PURPOSETo update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen (ER) and progesterone receptor (PgR) testing in breast cancer guideline.METHODSA multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature.RECOMMENDATIONSThe Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Background: Early stage breast cancer patients benefit from adjuvant chemotherapy, but delays in initiation of treatment can negatively impact outcomes. Delays may be more common in older women. In this study we evaluate the survival impact of delays in adjuvant chemotherapy initiation in patients over 65 years of age and identify factors associated with delays. Methods: Patients age 66 years and older diagnosed between 2001 and 2013 with localized or regional breast cancer were identified in the SEER-Medicare and Texas Cancer Registry-Medicare databases. All patients received adjuvant chemotherapy within 9 months of surgery. Patients were required to have continuous Medicare Parts A and B coverage and no HMO enrollment 12 months before and 12 months after diagnosis. We grouped patients according to time from surgery to chemotherapy in 4 groups: 0-30, 31-60, 61-90, and > 90 days. Delayed chemotherapy initiation was defined as > 90 days. We used multivariable logistic regression to identify predictors of delayed chemotherapy. We estimated overall survival (OS) and breast cancer-specific survival (BCSS) using Kaplan-Meier method. Inverse probability treatment weights were applied to survival analyses. Cox proportional hazard models were used to determine the association between delays in chemotherapy and outcome after adjustment for other variables. Results: 25,902 women were included in the analysis, and the median age was 71 years. The median time from surgery to chemotherapy was 43 days. From 2001-2013 this interval increased from 38 days to 47 days (p < 0.001). Chemotherapy delays were observed in 10.6% of the patients. In multivariable analysis, factors associated with an increased risk in chemotherapy delays included: older age, black or Hispanic race/ethnicity, being single, more comorbidities, hormone receptor positivity, mastectomy, Oncotype DX testing, and having a full state buy-in Medicare plan. Chemotherapy delay was associated with worse OS. The 5 year OS estimates for patients receiving chemotherapy 0-30, 31-60, 61-90 and > 90 days after surgery were 0.82, 0.81, 0.80 and 0.73 respectively (p < 0.001). A similar trend was seen with BCSS (p < 0.001). After multivariable adjustment chemotherapy delay was associated with worse OS (HR=1.32, 95%CI 1.24-1.40) and BCSS (HR=1.38, 95%CI 1.24 - 1.52) compared with patients in the 0-30 day category. In a stratified analysis among patients with known breast cancer subtype, we observed that a delay in adjuvant chemotherapy initiation was associated with worse OS among patients with hormone receptor-positive (HR=1.45, 95%CI 1.05-2.01), HER2-positive (HR=1.52, 95%CI 1.03-2.23), and triple negative (HR=1.90, 95%CI 1.32-2.73) breast cancer. Discussion: Delays in initiating adjuvant chemotherapy in older women with breast cancer are associated with worse OS and BCSS. Our data demonstrates that delays should be avoided and should encourage providers to initiate chemotherapy ≤ 90 days after surgery. In addition, the multidisciplinary medical team should be aware of the socioeconomic factors that may impact patients’ ability to receive timely treatment. Further studies should seek to elucidate the causes of these inequities in care. Citation Format: Demetria Smith-Graziani, Xiudong Lei, Sharon Giordano, Hui Zhao, Meghan Karuturi, Mariana Chavez-MacGregor. Delayed initiation of adjuvant chemotherapy in older women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-04.

Background We previously reported that in patients with HER2-positive (HER2+) locally advanced breast cancer treated with neoadjuvant trastuzumab-containing regimens, high HER2 to centromere enumerator probe 17 ratio on fluorescence in situ hybridization (HER2 FISH ratio) was an independent predictor of high pathologic complete response (pCR) rate, which translated into improved recurrence-free survival (RFS). We sought to determine whether high HER2 FISH ratio is a predictor of pCR and prognosis in patients with HER2+ nonmetastatic inflammatory breast cancer (IBC) and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab. Materials and Methods This study included all patients with histologically proven stage III, HER2+ primary IBC, and non-IBC treated with neoadjuvant chemotherapy with or without trastuzumab and definitive surgery during 1999–2012. Univariate and multivariate logistic regression models were applied to assess the effect of covariates on pCR. Kaplan-Meier estimates with log-rank test were employed for survival analysis. Univariate and multivariate Cox proportional hazards models were used to assess the effect of covariates on RFS and overall survival (OS). Results The study included 555 patients with stage III, HER+ breast cancer, 181 patients with IBC, and 374 with non-IBC. In the IBC cohort, HER2 FISH ratio was not significantly associated with pCR, RFS, or OS. In the non-IBC cohort, higher HER2 FISH ratio was significantly associated with higher pCR rate and longer OS. Conclusion HER2 FISH ratio showed prognostic value among patients with HER2+ non-IBC but not HER2+ IBC treated with neoadjuvant chemotherapy. This disparity may be due to the underlying aggressive nature of IBC. Implications for Practice The findings of this study indicate that the HER2 to fluorescence in situ hybridization ratio as a continuous variable has promise as a predictor of pathologic complete response to neoadjuvant chemotherapy in patients with HER2-positive (HER2+) noninflammatory breast cancer (non-IBC) regardless of the results on HER2 immunohistochemical testing. In the future, some patients with HER2+ non-IBC and a high HER2 FISH ratio might even be offered personalized treatment options, such as nonsurgical treatment.

Purpose.—To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer guideline.Methods.—A multidisciplinary international Expert Panel was convened to update the clinical practice guideline recommendations informed by a systematic review of the medical literature.Recommendations.—The Expert Panel continues to recommend ER testing of invasive breast cancers by validated immunohistochemistry as the standard for predicting which patients may benefit from endocrine therapy, and no other assays are recommended for this purpose. Breast cancer samples with 1% to 100% of tumor nuclei positive should be interpreted as ER positive. However, the Expert Panel acknowledges that there are limited data on endocrine therapy benefit for cancers with 1% to 10% of cells staining ER positive. Samples with these results should be reported using a new reporting category, ER Low Positive, with a recommended comment. A sample is considered ER negative if < 1% or 0% of tumor cell nuclei are immunoreactive. Additional strategies recommended to promote optimal performance, interpretation, and reporting of cases with an initial low to no ER staining result include establishing a laboratory-specific standard operating procedure describing additional steps used by the laboratory to confirm/adjudicate results. The status of controls should be reported for cases with 0% to 10% staining. Similar principles apply to PgR testing, which is used primarily for prognostic purposes in the setting of an ER-positive cancer. Testing of ductal carcinoma in situ (DCIS) for ER is recommended to determine potential benefit of endocrine therapies to reduce risk of future breast cancer, while testing DCIS for PgR is considered optional. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Tumor biology is an important prognostic factor in breast cancer. This study aimed to compare three staging systems incorporating both biologic factors and anatomic staging (AJCC 8th-edition pathologic prognostic staging, Bioscore, and Risk Score) in a large population-based cohort. The Surveillance, Epidemiology and End Results program was used to select patients with primary stages 1–4 breast cancer diagnosed in 2010. Patients with inflammatory carcinoma, those with missing data for biologic factors, and those with stages 1–3 disease not treated with surgery were excluded from the study. Estimates of 5-year disease-specific survival (DSS) were calculated using the Kaplan–Meier method. The Harrel concordance index (C-index) and the Akaike Information Criterion were used to compare each model in terms of predicting DSS. The study included 21,901 patients with a median age of 60 years. The median follow-up period was 52 months. All the staging models stratified DSS, with a stepwise decrease in DSS for each increase in risk category or score. The C-index of each model incorporating biologic factors was higher than the C-index for anatomic staging alone (C-index: 0.832 vs. 0.856 for AJCC pathologic prognostic staging, 0.856 for Bioscore, and 0.864 for Risk Score, all p

The American Joint Committee on Cancer (AJCC) breast cancer pathological prognostic stage, which incorporates biologic factors, was developed using data from patients undergoing upfront surgery, and its application in patients receiving neoadjuvant chemotherapy (NAC) is unknown. We previously developed the Neo-Bioscore, incorporating clinical and pathological TNM categories with biologic factors, to improve the prognostic stratification of NAC patients. This study was undertaken to evaluate the use of available staging models incorporating biologic factors in NAC patients. Patients treated with NAC between 2005 and 2012 at MD Anderson (n = 2363) were staged using the Neo-Bioscore and the AJCC 8th edition: (1) clinical anatomic stage; (2) pathological anatomic stage; (3) clinical prognostic stage; and (4) pathological prognostic stage. Five-year disease-specific survival (DSS) and overall survival (OS) rates, along with Harrell’s concordance index (C-index), were estimated. A National Cancer Database (NCDB) cohort (n = 12,887) treated with NAC between 2010 and 2013 was used for validation. In the MD Anderson cohort, staging systems incorporating biologic factors better predicted DSS (bias-corrected C-index: pathological prognostic stage = 0.8026; Neo-Bioscore = 0.7483) and OS (bias-corrected C-index: pathological prognostic stage = 0.7780; Neo-Bioscore = 0.7260) than those using anatomic factors only. Similar results were seen in the NCDB cohort. In pairwise comparisons, the pathological prognostic stage was significantly better (p

Importance: As the COVID-19 pandemic continues, understanding the clinical outcomes of patients with cancer and COVID-19 has become critically important. Objective: To compare the outcomes of patients with or without cancer who were diagnosed with COVID-19 and to identify the factors associated with mortality, mechanical ventilation, intensive care unit (ICU) stay, and hospitalization. Design, Setting, and Participants: This cohort study obtained data from the Optum de-identified COVID-19 electronic health record data set. More than 500 000 US adults who were diagnosed with COVID-19 from January 1 to December 31, 2020, were analyzed. Exposures: The patient groups were (1) patients without cancer, (2) patients with no recent cancer treatment, and (3) patients with recent cancer treatment (within 3 months before COVID-19 diagnosis) consisting of radiation therapy or systemic therapy. Main Outcomes and Measures: Mortality, mechanical ventilation, ICU stay, and hospitalization within 30 days of COVID-19 diagnosis were the main outcomes. Unadjusted rates and adjusted odds ratios (ORs) of adverse outcomes were presented according to exposure group. Results: A total of 507 307 patients with COVID-19 were identified (mean [SD] age, 48.4 [18.4] years; 281 165 women [55.4%]), of whom 493 020 (97.2%) did not have cancer. Among the 14 287 (2.8%) patients with cancer, 9991 (69.9%) did not receive recent treatment and 4296 (30.1%) received recent treatment. In unadjusted analyses, patients with cancer, regardless of recent treatment received, were more likely to have adverse outcomes compared with patients without cancer (eg, mortality rate: 1.6% for patients without cancer, 5.0% for patients with no recent cancer treatment, and 7.8% for patients with recent cancer treatment). After adjustment, patients with no recent cancer treatment had similar or better outcomes than patients without cancer (eg, mortality OR, 0.93 [95% CI, 0.84-1.02]; mechanical ventilation OR, 0.61 [95% CI, 0.54-0.68]). In contrast, a higher risk of death (OR, 1.74; 95% CI, 1.54-1.96), ICU stay (OR, 1.69; 95% CI, 1.54-1.87), and hospitalization (OR, 1.19; 95% CI, 1.11-1.27) was observed in patients with recent cancer treatment. Compared with patients with nonmetastatic solid tumors, those with metastatic solid tumors and hematologic malignant neoplasms had worse outcomes (eg, mortality OR, 2.36 [95% CI, 1.96-2.84]; mechanical ventilation OR, 0.87 [95% CI, 0.70-1.08]). Recent chemotherapy and chemoimmunotherapy were also associated with worse outcomes (eg, chemotherapy mortality OR, 1.84 [95% CI, 1.51-2.26]). Conclusions and Relevance: This cohort study found that patients with recent cancer treatment and COVID-19 had a significantly higher risk of adverse outcomes, and patients with no recent cancer treatment had similar outcomes to those without cancer. The findings have risk stratification and resource use implications for patients, clinicians, and health systems.

OBJECTIVE: To describe disparities in patterns of hospice use and end-of-life costs among ovarian cancer patients. METHODS: Using Texas Cancer Registry-Medicare data, ovarian cancer patients deceased 2005–2012 with >12 months of continuous Medicare coverage before death were included. Descriptive statistics and multivariable logistic regressions were used to evaluate patterns of hospice use. Cost and resource utilization was obtained from Medicare claims and analyzed using a non-parametric Mann-Whitney test. RESULTS: 2,331 patients were assessed: 1,788 (77%) white, 359 (15%) Hispanic, 158 (7%) black and 26 (1%) other. 1,756 (75%) enrolled in hospice prior to death but only 1,580 (68%) died with hospice. 176 (10%) of 1756 patients unenrolled and died without hospice. 346 (20%) unenrolled from hospice multiple times. From 2008–2012, patients were less likely to unenroll from hospice prior to death. Black patients were more likely to unenroll from hospice prior to death (OR 2.07 [1.15–3.73]; p=0.02) compared to white patients. The median amount paid by Medicare during the last six months of life was $38,530 for those in hospice compared to $49,942 if never enrolled in hospice (p

BACKGROUND: Raloxifene is a selective estrogen receptor modulator that has demonstrated to reduce breast cancer risk and reduce the incidence of vertebral fractures. Based on these effects, raloxifene is used as a risk reduction agent and to prevent osteoporosis in postmenopausal women. Little is known about the raloxifene adherence rates or the relationship between adherence and breast cancer incidence. METHODS: Women 60 years or older without a breast cancer history were identified in the MarketScan database (2008-2015). We identified women who received raloxifene by searching for prescription claims. Proportion of days covered (PDC) were calculated, adherence was defined as a PDC >80% in the first year after initial prescription claim. We identified factors associated with adherence. ICD-9 codes were used to identify incident cases of invasive breast cancer and cumulative incidence rates were calculated. A multivariable Cox model with propensity score method (matching variables included year of claim, age, comorbidities and family history of breast cancer) was used to evaluate the association between raloxifene adherence and breast cancer risk. All statistical tests were two-sided. RESULTS: A total of 16,179 women were included in the analysis. We identified that during the first year of treatment 6,716 (40.2%) women had a PDC >80% and thus were considered to be adherent. Factors associated with increased adherence included the use of generic drug, mail order of 90 days supply and family history of breast cancer (all p CONCLUSIONS: Among women 60 years of age or older receiving raloxifene, adherence to therapy was associated with lower risk of invasive breast cancer. Efforts to ensure adherence and compliance are crucial so patients can receive full benefit from this therapy. Citation Format: Chavez-MacGregor M, Lei X, Zhao H, Bevers TB, Brewster A, Giordano SH. Impact of raloxifene adherence in breast cancer risk [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-02.

Background: Pertuzumab (P) in combination with trastuzumab (H) based chemotherapy is FDA-approved as a standard neoadjuvant treatment for patients with clinical stage II-III HER2-positive (HER2+) breast cancer (BC). The goal of this study was to evaluate the pathologic complete response (pCR) rate for neoadjuvant HP-containing regimens compared to H-containing regimens and report the 3-year relapse-free survival (RFS) for patients who had a pCR compared to those with residual disease (RD). Methods: All patients with stage II-III non-inflammatory HER2+ BC who received neoadjuvant H-containing or HP-containing therapy and underwent definitive breast and axillary surgery were identified from 2005 to 2016 through an institutional database. Medical records were examined for patient demographics, breast cancer stage, pathology results, surgical outcomes, and treatment details. pCR was defined as ypT0/is, ypN0. RFS was defined as the interval from surgery to date of last followup or death from any cause. Descriptive statistics, Cox proportional hazards, and Kaplan-Meier estimates were used for statistical analysis. Results: Patient characteristics and results by pCR or RD status are shown in the table below. The median age was 51 (22-84) years for the HP group and 50 (21-87) years for the H group. The median follow-up time was 1.9 (0-4.2) years for the HP group and 5.3 (0.1-12) years for the H group. For the HP group, the 3-year RFS was 98% (95% CI: 95, 100) for the pCR group and 90% (95% CI: 83, 97) for the RD group; HR 0.17 (0.04, 0.82), p=0.012. For the H group, the 3-year RFS was 91% (95% CI: 88,94) for the pCR group and 75% (95% CI: 71-79) for the RD group; HR 0.31 (0.22, 0.44), p Conclusion: Patients who achieve pCR have an improved 3-year RFS compared to patients who have RD. Treatment with HP-containing neoadjuvant regimens is associated with a high 3-year RFS. VariableHP (n=215)H (n=807) pCR n=121RD n=94pCR n=399RD n= 408Age at Diagnosis Citation Format: Murthy RK, Raghavendra AS, Hess KR, Barcenas CH, Lim B, Moulder SL, Giordano SH, Mittendorf EA, Thompson A, Ueno NT, Valero V, Litton JK, Tripathy D, Chavez-Macgregor M. 3-year relapse-free survival of stage II-III HER2-neu positive breast cancer treated with pertuzumab and trastuzumab-containing neoadjuvant therapy compared to trastuzumab-containing therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-04.

Objectives Breast cancer (BC) is the leading cause of morbidity and mortality. Neurological symptoms are highly feared because they are associated with central nervous system metastases (CNSm). So, we aimed to analyze the association of neurological symptoms with CNSm. Patients & Methods Patients with BC referred for a neuro-oncological evaluation at a cancer referral center from June 2012 to December 2017 were included. Demographic, oncological history, comorbidities, clinical symptoms and signs, and their correlation with CNSm were prospectively acquired during consultation in a computerized database. Analyses included descriptive observations, bivariate, and logistic linear regression tests that compared associations. Results A total of 857 patients with BC were referred for assessment. The most frequently occurring symptoms included headache, focal motor weakness, focal-sensitive complaints, and visual complaints. Of the 1029 neuro-oncology diagnoses made, the most common were CNSm, primary headache, and chemotherapy-induced neuropathy. The risk factors associated with CNSm in patients with neurological symptoms were HER2+, younger age at cancer diagnosis, presence of extracranial metastases, and >1 neurological symptom (mainly headache: hazard ratio (HR), 2.1 [95% confidence interval (CI), 1.5–2.7]; visual complaints: HR, 2.3 (95%CI, 1.2–4.2); and ataxia: HR, 2.1 (95%CI,1.04–4.3). Conclusions Clinical symptoms and cancer characteristics were correlated with the development of CNSm. Specific risk and protective factors were identified. Among BC patients with neurological symptoms, CNSm should always be considered, especially in patients with certain oncological and clinical features.

PURPOSE The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; P < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab. RECOMMENDATIONS Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars. Additional information can be found at www.asco.org/breast-cancer-guidelines

Background Delays in the initiation of therapy among patients with early stage breast cancer (BC) can negatively affect outcomes. Patients treated with neoadjuvant systemic chemotherapy (NSC) usually display tumors with high-risk features. Considering these high-risk characteristics and the evidence supporting adverse outcomes associated with delays in adjuvant chemotherapy initiation, we sought to determine whether a delay in NSC initiation is associated with overall survival (OS). Methods We identified patients diagnosed between January 1995 and December 2015 with invasive primary BC (stage I–III) who received NSC at MD Anderson Cancer Center. Patients were categorized according to their time from BC diagnosis to NSC (in days) into three subgroups: 0-30, 31–60, and ≥61 days. Primary endpoint was OS. Descriptive statistics and Cox's proportional hazard models were used. Results A total of 5,137 patients were included. Median follow-up was 6.5 years. The 5-year OS estimates according to time to NSC were 87%, 85%, and 83% in patients who received NSC within 0–30, 31–60, and ≥61 days after diagnosis, respectively (p = .006). In multivariable analysis, compared with time to NSC of 0–30 days, delayed NSC ≥61 days was associated with an increased risk of death (31–60 days: hazard ratio [HR] = 1.05 [95% confidence interval (CI) 0.92–1.19]; ≥61 days, HR = 1.28 [95% CI 1.06–1.54]). In stratified analyses, the association between delay in NSC initiation and increased risk of death was statistically significant for patients with stage I and II BC (31–60 days: HR = 1.22 [95% CI 1.02–1.47]; ≥61 days, HR = 1.41 [95% CI 1.07–1.86]) and among patients with HER2-positive tumors ( ≥61 days, HR = 1.86 [95% CI 1.21–2.86]). Conclusion A delay in NSC initiation of more than 61 days after BC diagnosis was associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus on coordination of care and patient-centered, timely treatment planning and delivery. Implications for Practice The results of this study showed that a delay in neoadjuvant systemic chemotherapy initiation of more than 61 days after breast cancer diagnosis is associated with an increased risk of death; therefore, efforts must focus on early initiation of therapy, which should be a priority. Multidisciplinary teams must enhance coordination of care and patient-centered, timely treatment planning and delivery.

The SSO-ASTRO consensus guideline on invasive breast cancer defined negative margin as no ink on tumor, obviating the need for reexcision in some patients. We evaluated the impact of these recommendations on the rates of reexcision in older breast cancer patients undergoing breast-conserving surgery (BCS). Women age ≥ 66 years with stage I–II breast cancer who underwent BCS and radiation were identified in the SEER-Medicare linked database (2012–2015). We divided patients into three cohorts: pre-guideline (January 2012 to September 2013), peri-guideline (October 2013 to March 2014), and post-guideline (April 2014 to September 2016). Descriptive statistics were used, and the relative change in reexcision rate between the pre- and post-guideline periods was calculated. Multivariable logistic regression was used to evaluate factors associated with risk of reexcision. A total of 11,639 patients were included (pre-guideline, N = 5211; peri-guideline, N = 1366; post-guideline, N = 5062); overall, 21.7% of patients underwent reexcision. The reexcision rates decreased after the guideline was published (23.5% vs. 19.3%, p < 0.001). In the multivariable model, BCS during the post-guideline period was associated with a statistically significant decreased risk of reexcision (RR = 0.84; 95% CI 0.78–0.90). Lobular histology was associated with a higher risk of reexcision (RR = 1.32; 95% CI 1.19–1.46), and greater surgeon volume was associated with lower risk of reexcision (RR = 0.92; 95% CI 0.85–1.0). Among older breast cancer patients undergoing BCS for invasive cancer, reexcision rates decreased with the dissemination of the SSO-ASTRO consensus guideline. Identifying factors associated with higher rates of reexcision could improve guideline compliance and reduce the frequency of unnecessary interventions in older patients.

Background Adjuvant chemotherapy benefits early‐stage breast cancer (BC) patients. Older women receive guideline‐adherent treatment less frequently and experience treatment delays more frequently. We evaluated factors associated with delaying adjuvant chemotherapy and the delays’ survival impact in a large population–based cohort of elderly BC patients. Methods Patients age >66 years diagnosed 2001‐2015 with localized or regional BC were identified in the SEER‐Medicare and Texas Cancer Registry‐Medicare databases. Time from surgery to chemotherapy (TTC) was categorized into four groups: 0‐30, 31‐60, 61‐90, and >90 days. We identified predictors of delays, estimated overall (OS) and BC‐specific (BCSS) survival, and determined the association between TTC and outcome adjusting for other variables. Results Among 28,968 women (median age 71 years), median TTC was 43 days. 10.7% of patients experienced TTC >90 days. Older age, Black or Hispanic race/ethnicity, unmarried status, more comorbidities, hormone receptor‐positivity, mastectomy, Oncotype DX testing, and full state buy‐in were associated with increased risk of delay. Five‐year OS estimates by TTC group were 0.82, 0.81, 0.80, and 0.74, respectively (p, We evaluated the factors associated with delays in the initiating adjuvant chemotherapy and the survival impact of delays in a large population‐based cohort of elderly breast cancer patients. We found chemotherapy delays beyond 90 days after surgery negatively affected survival, and delays were associated with clinical and socioeconomic factors.

Background Older patients with cancer are at risk for increased side effects of treatment. Our goal was to inform treatment for older patients by analyzing the relationship between chemotherapy regimen and hospitalization among older women receiving palliative cytotoxic chemotherapy for breast cancer. Method We identified women aged 66-99 years with stage IV de novo breast cancer diagnosed between 2010 and 2013 who received any of the 10 most common cytotoxic chemotherapy-containing regimens in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. The primary outcome was hospitalization or death within 30 days of starting a new line of chemotherapy. Generalized linear mixed effects models with patient-specific random effects were used for multivariable analysis of the association between chemotherapy regimen and this outcome. Additional covariates included number of prior lines of therapy; time since diagnosis; hormone receptor and HER2 status; sites of metastatic disease; and age, race, and marital status. The unit of analysis was each new line of chemotherapy. Results Of 972 lines of chemotherapy initiated among 693 patients, 188 (19%) were followed by hospitalization or death within 30 days. After adjustment, there was significant variation in this outcome by chemotherapy regimen (P = .03); compared with capecitabine, hospitalization/death rates were higher with cyclophosphamide + docetaxel (odds ratio [OR], 2.71; 95% confidence interval [CI], 1.31-5.59), cyclophosphamide + doxorubicin (OR, 2.45; 95% CI, 1.19-5.03), docetaxel (OR, 2.49; 95% CI, 1.19-5.21), and gemcitabine (OR, 3.51; 95% CI, 1.72-7.19). Conclusion Treatment regimen was associated with significant variation in 30-day hospitalization or death among older women receiving cytotoxic chemotherapy for stage IV de novo breast cancer.

Background An increasing proportion of human epidermal growth receptor 2 (HER2) positive (HER2+) metastatic breast cancer (MBC) is diagnosed as de novo stage IV disease. We hypothesize that a subset of these patients who achieve no evidence of disease (NED) status after multimodality HER2-targeted treatments may have prolonged progression-free survival (PFS) and overall survival (OS). Materials and Methods Patients with de novo stage IV, HER2+ MBC (n = 483) diagnosed between 1998 and 2015 were identified at two institutions (Yale and MD Anderson Cancer Centers). Clinical variables, treatment details, and survival outcomes were compared between those who achieved NED and those who did not. Results All patients received trastuzumab, and 20% also received pertuzumab as first-line therapy. The median OS was 5.5 years (95% confidence interval [Cl]: 4.8–6.2). Sixty-three patients (13.0%) achieved NED; their PFS and OS rates were 100% and 98% (95% CI: 94.6%–100%), respectively, at 5 years and remained the same at 10 years. For patients with no NED (n = 420), the PFS and OS rates were 12% (95% CI: 4.5%–30.4%) and 45% (95% CI: 38.4%–52.0%) at 5 years and 0% and 4% (95% CI, 1.3%–13.2%) at 10 years, respectively. NED patients more frequently had solitary metastasis (79% vs. 51%, p = .005) and surgery to resect cancer (59% vs. 22%, p ≤ .001). In multivariate analysis, NED status (hazard ratio [HR]: 0.014, p = .0002) and estrogen receptor positive status (HR: 0.72; p = .04) were associated with prolonged OS. Conclusion Among patients with de novo stage IV, HER2+ MBC, those who achieve NED status have a very high PFS and OS. Further randomized studies are required to fully understand the impact of systemic or locoregional therapy on achieving these excellent long-term outcomes. Implications for Practice In this retrospective review at two institutions, it was demonstrated that 13% of patients with de novo stage IV, human epidermal growth receptor 2 positive metastatic breast cancer achieved no evidence of disease (NED) status with trastuzumab-based therapy plus/minus local therapies, and these patients had a very high progression-free survival (100%) and overall survival (98%) at both the 5- and 10-year time points. Achieving NED status may be an important therapeutic goal. However, further randomized studies are required to fully understand the impact of systemic or locoregional therapy on achieving these excellent long-term outcomes.

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

The introduction of trastuzumab for the adjuvant treatment of tumors with amplification of HER2/neu has been one of the most exciting advances in systemic treatment in the history of breast cancer and has transformed the natural history of HER2/neu-positive (HER2+) breast cancer (BC). There have been several recent advances in the adjuvant treatment of HER2+ BC and herein we review recently reported clinical trials focusing on the impact of expanding therapeutic options with attention to optimal sequence of the available treatment options and clinical aspects of escalating or de-escalating therapy for patients based on their level of risk. Two major clinical trials (APHINITY and EXTENET) reported modest improvements in disease-free survival (DFS) leading to FDA approval of pertuzumab in the adjuvant setting and neratinib in the extended adjuvant setting for HER2+ BC. In addition to the previously established utility of trastuzumab in combination with chemotherapy in the adjuvant setting, we now have expanded options with two additional agents. However, it has become challenging to appropriately sequence therapies and select patients who will truly benefit from receipt of additional therapies and for which patients de-escalation of therapy may be possible. Although significant advances have been made in the treatment of HER2+ BC since the introduction of trastuzumab over the past 20 years, patients do still harbor primary resistance and experience recurrence following optimal treatment. In this review, we seek to provide a practical approach for clinicians to optimally utilize the available adjuvant anti-Her2 drugs with the data currently available.

BACKGROUND Racial disparities in cancer outcomes have been described. To the authors' knowledge, it remains unclear whether patients of Hispanic ethnicity have better or worse survival outcomes. In the current study, the authors evaluated whether Hispanic participants in SWOG clinical trials had different survival outcomes compared with non-Hispanics. METHODS Adult patients registered in SWOG phase 2/3 clinical trials between 1986 and 2012 were analyzed. Studies of similar histology and stage of disease were combined. Within each analysis, Kaplan-Meier survival curves were generated to examine differences in outcome by ethnicity. Multivariate Cox regression was used to estimate the association between ethnicity and survival outcomes, controlling for major disease-specific prognostic factors and demographic variables plus area-level income and education to account for socioeconomic status. RESULTS A total of 29,338 patients registered to 38 trials were included; 5% of these patients were Hispanic. Hispanic patients were more likely to be younger and from areas of lower income and education (all P

Background Chemotherapy for early breast cancer is associated with a small risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). The aim of this study was to determine the risk of developing AML or MDS after modern adjuvant chemotherapy in older breast cancer patients and to further define the risk of individual chemotherapy regimens. Methods Patients diagnosed with stage I to III breast cancer from 2003 to 2009 were identified in the Surveillance, Epidemiology, and End Results-Medicare and Texas Cancer Registry-Medicare linked databases. The development of AML/MDS, chemotherapy use, and comorbidities were identified with International Classification of Diseases, Ninth Revision and Healthcare Common Procedure Coding System codes. Analyses included descriptive statistics, cumulative incidences, and Cox proportional hazards models to estimate the hazard of AML/MDS after adjustments for clinically relevant covariates. Results In all, 92,110 patients were included; after a median follow-up of 85 months, the overall rates per 1000 person-years were 0.65 for AML and 1.56 for MDS. Patients who received an anthracycline (A) or anthracycline and taxane (A+T) regimen were more likely to develop AML (hazard ratio [HR] for A, 1.70; 95% confidence interval [CI], 1.16-2.50; HR for A+T, 1.68; 95% CI, 1.22-2.30) or MDS (HR for A, 2.18; 95% CI, 1.70-2.80; HR for A+T, 1.62; 95% CI, 1.29-2.03) than patients who did not receive chemotherapy. Patients using docetaxel and cyclophosphamide (TC) were not at increased risk for AML or MDS. Conclusions Adjuvant chemotherapy is associated with a small but significant increase in the risk of AML and MDS, especially with regimens that include A. Longer follow-up is needed to confirm that risk is not increased with the recently adopted TC regimen. Cancer 2018;124:899-906. © 2017 American Cancer Society.

BACKGROUND Treatment guidelines for colon cancer recommend colectomy with lymphadenectomy of at least 12 lymph nodes for patients with stage I to stage III disease as surgery adherence (SA) and adjuvant chemotherapy for individuals with stage III disease. Herein, the authors evaluated adherence to these guidelines among older patients in Texas with colon cancer and the associated survival outcomes. METHODS Using Texas Cancer Registry data linked with Medicare data, the authors included patients with AJCC stage II and III colon cancer who were aged ≥66 years and diagnosed between 2001 and 2011. SA and adjuvant chemotherapy adherence rates to treatment guidelines were estimated. The chi-square test, general linear regression, survival probability, and Cox regression were used to identify factors associated with adherence and survival. RESULTS The rate of SA increased from 47.2% to 84% among 6029 patients with stage II or stage III disease from 2001 to 2011, and the rate of adjuvant chemotherapy increased from 48.9% to 53.1% for patients with stage III disease during the same time period. SA was associated with marital status, tumor size, surgeon specialty, and year of diagnosis. Patient age, sex, marital status, Medicare state buy-in status, comorbidity status, and year of diagnosis were found to be associated with adjuvant chemotherapy. The 5-year survival probability for patients receiving guideline-concordant treatment was the highest at 87% for patients with stage II disease and was 73% for those with stage III disease. After adjusting for demographic and tumor characteristics, improved cancer cause-specific survival was associated with the receipt of stage-specific, guideline-concordant treatment for patients with stage II or stage III disease. CONCLUSIONS The adherence to guideline-concordant treatment among older patients with colon cancer residing in Texas improved over time, and was associated with better survival outcomes. Future studies should be focused on identifying interventions to improve guideline-concordant treatment adherence. Cancer 2017. © 2017 American Cancer Society.

e18565 Background: The persistent racial and socioeconomic status (SES) disparities in breast cancer outcomes are partially attributed to propensity towards more aggressive cancers or presentation at higher stages among these groups. Chronic stressors related to race and SES are another major mechanism underlying these inequities. This study aims to examine the effect of race and SES within the AJCC 8th-edition staging system, which incorporates anatomic extent of disease and tumor biology. Methods: The SEER breast cancer database linked with county-level census data was used to identify patients with invasive breast cancer from 2010-2015. The database includes a composite SES-index which was analyzed in quintiles. Cox proportional-hazards regression was used to estimate disease-specific survival (DSS). Results: 259,852 patients were included: 176,369 (67.9%) non-Hispanic white, 28,510 (11.0%) Black, 29,737 (11.4%) Hispanic, and 22,887 (8.8%) Asian. Black race, lower SES, public insurance, lower education, and increased poverty were associated with decreased DSS. Adjusted survival analysis for patient, SES, tumor, and treatment characteristics demonstrated that patients of black race had inferior DSS within each stage. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS [Table]. Conclusions: Racial and SES disparities in breast cancer-specific mortality were evident across all stages of disease. Future efforts to improve breast cancer outcomes should systematically assess and address racial and socioeconomic factors as fundamental drivers of inequitable outcomes. Adjusted 5-year DSS Estimates, Stratified by Race and SES.[Table: see text]

BACKGROUND Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]–positive/hepatitis B core antibody [anti-HBc]–positive) or past (HBsAg-negative/anti-HBc–positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017. © 2017 American Cancer Society.

BACKGROUND: The current American Joint Committee on Cancer (AJCC) breast cancer staging system provides important prognostic information, however its use is limited by the lack of data incorporating prognostic and predictive biological markers. In this study we sought to determine the relationship between stage, breast cancer subtype, grade and outcome in a large population-based cohort, and to develop a risk score point-based system incorporating biological factors to the current AJCC staging system. METHODS: Patients diagnosed with primary breast cancer stage I-IV, between 2005-2008 were identified in the California Cancer Registry. For patients with stage I-III disease, pathological stage was recorded. For those with stage IV, clinical stage was used. 5 year-breast cancer specific survival (BCSS) and overall survival (OS) rates were determined for each potential TNM combination according to breast cancer subtype. Cox proportional hazard models were used to identify independent predictors of outcome. A risk score point-based system (range 0-3 points) was created to complement the current anatomic AJCC staging system. One point was assigned for each one of the following tumor characteristics: hormone receptor (HR)-negative status, HER2-negative status and grade 3. Survival probabilities between groups were compared using log-rank test. Multivariable analysis models according to stage and risk score were performed for BCSS and OS. RESULTS: A total of 43,938 patients were included. The 5-year BCSS and OS for each TNM combination differed according to breast cancer subtype. The best outcomes were seen among HR-positive patients followed closely by those with HER2-positive and HR-positive tumors with the worst outcomes observed among patients with triple negative tumors. In a multivariable model, after adjusting for stage, treatment variables and other important confounders, ER negative status (OR 2.14; 95%CI 1.98-2.30), HER2-negative status (OR= 1.24; 95%CI1.14-1.34) and grade 3 (OR=2.03; 95% CI 1.88-2.20) were independent predictors of BCSS. Our risk score system separated patients into 4 risk groups within each stage category (all P Hazard ratios for BCSS according to stage and risk score.Stage/Risk ScoreHazard Ratio95%CII-0Reference I-10.630.42-0.97I-22.811.87-4.23I-34.902.79-8.61IIA-03.652.26-5.91IIA-12.241.50-3.33IIA-25.873.94-8.73IIA-39.356.24-13.99IIB-04.763.13-7.24IIB-15.043.37-7.53IIB-29.465.63-15.92IIB-314.599.78-21.79IIIA-09.136.12-13.62IIIA-17.384.92-11.06IIIA-212.017.14-20.19IIIA-332.5421.59-49.04IIIB-018.9712.62-28.52IIIB-119.0512.68-28.61IIIB-228.3418.91-42.47IIIB-335.6121.33-59.43IIIC-011.525.84-22.74IIIC-115.766.07-40.94IIIC-226.7716.74-42.83IIIC-356.6336.60-87.60IV-049.9330.64-81.36IV-167.4545.36-100.23IV-2107.6272.36-60.07IV-3164.04107.18-251.04 CONCLUSIONS: Incorporating biological factors to the current AJCC staging system provides more accurate prognostic information and reflects current treatment practice. The proposed risk score improves the AJCC breast cancer staging system and should be incorporated in the upcoming revision. Citation Format: Chavez-MacGregor M, Mittendorf EA, Clarke CA, Lichensztajn DY, Hunt KK, Giordano SH. Improving the AJCC breast cancer staging system by incorporating tumor biomarkers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-02.

BACKGROUND Invasive disease-free survival (IDFS) rates are excellent in patients with breast cancer (BC) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), axillary lymph node-negative (LN-) tumors with a 21-gene expression assay recurrence score (RS) of 0 to 10. However, to the authors' knowledge, the outcomes among patients with an RS of 11 to 25 who are treated with endocrine therapy alone are unknown. METHODS In this retrospective single-institution study, the authors described the characteristics of patients with HR+, HER2-, LN- BC who underwent a 21-gene expression assay. In addition, among those individuals diagnosed between 2005 and 2011, we measured IDFS, recurrence-free survival, distant recurrence-free survival, and overall survival rates, focusing on patients with an RS of 11 to 25 by receipt of chemotherapy. The Kaplan-Meier method was used to estimate survival rates and multivariable Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals (95% CIs). RESULTS Among 1424 patients, the RS distribution was 0 to 10 in 297 patients (21%), 11 to 25 in 894 patients (63%), and >25 in 233 patients (16%); of these, 1.7%, 15%, and 73.4% of patients, respectively, received chemotherapy. With a median follow-up of 58 months, those patients with an RS of 11 to 25 had an IDFS rate at 5 years of 92.6% (95% CI, 89.6%-94.7%), which was comparable between those who received chemotherapy and those who did not. The hazard ratios of the effect of chemotherapy were 1.64 for IDFS (95% CI, 0.73-3.71), 1.46 for recurrence-free survival (95% CI, 0.41-5.23), 1.25 for distant recurrence-free survival (95% CI, 0.32-4.92), and 2.19 for overall survival (95% CI, 0.44-11.0). CONCLUSIONS The results of the current study demonstrate similar outcomes with or without chemotherapy in patients with HR+, HER2-, LN- BC who have an RS of 11 to 25, but a benefit from chemotherapy in this group cannot be ruled out. Cancer 2017;123:2422–31. © 2017 American Cancer Society.

Background: The 7th edition AJCC staging system provides prognostic information based on the anatomic extent of disease determined by the tumor size (T), lymph node status (N), and presence or absence of metastatic disease (M). Tumor biology, including grade, estrogen receptor (ER) status and HER2 status, which are known to have prognostic and predictive value, are not incorporated. This study was undertaken to evaluate a risk score that takes into account the tumor grade and other biomarkers that can be added to the current anatomic TNM staging system to improve stratification of patients with respect to disease specific survival (DSS) and overall survival (OS). Methods: A prospectively maintained database was used to identify 3,327 patients with non-metastatic invasive breast cancer who underwent surgery as a first intervention from January 2007 through December 2013. Clinicopathologic data were recorded including: age, grade, ER status, HER2 status, and pathologic stage. Pathologic stage was determined according to the 7th edition of the AJCC staging guidelines. ER status was recorded as the percentage of cells staining positive by immunohistochemistry (IHC). Prior to 2010, tumors were classified as ER positive if there was >10% staining. A cut-off of 1% was used for patients treated after 2010, consistent with the change in American Society of Clinical Oncology (ASCO) guidelines. HER2 status was defined as positive if 3+ on immunohistochemistry or gene amplification was shown on fluorescence in situ hybridization. A risk score was calculated by assigning one point for each of the following tumor characteristics: ER-negative status, HER2 negative status and grade 3. Univariate survival analyses according to AJCC stage (I, IIA, IIB, IIIA and IIIC) and risk score (0-3) were performed for DSS and OS using the Kaplan Meier method. Results: Median follow-up time was 5.0 years (range, 0.1 to 8.8). Five year DSS for the entire cohort was 97.9% (95% CI: 97.3%-98.4%). The distribution in risk score in the entire cohort was: risk score 0=81 (2.4%), 1=2289 (68.8%), 2=683 (20.5%), and 3= (8.3%). As shown in the table, for all AJCC stages, the 5-yr DSS and 5-yr OS varied according to risk score (p StageRisk Scoren5-yr DSS (%)95% CI5-yr OS (%)95% CII (IA and IB)036100 9780.4-99.6 1117399.498.7-99.796.795.4-97.6 227498.896.4-00.694.691.0-06.8 311996.691.1-98.793.887.5-97.0IIA031100 96.879.2-99.5 163499.497.5-99.897.194.7-98.4 223697.593.2-99.194.188.7-97.0 39891.081.8-95.788.278.5-93.8IIB011100 100 130996.992.6-98.894.689.6-97.2 210792.983.6-97.189.380.1-94.4 34091.575.6-97.291.575.6-97.2IIIA03100 100 113498.388.2-99.891.582.6-96.0 25092.277.2-97.590.375.7-96.3 3768.621.3-91.268.621.3-91.2IIIC00 13992.272.1-98.084.463.7-93.9 21680.851.4-93.480.851.4-93.4 31033.36.3-64.633.36.2-64.6 Conclusion: The current study demonstrates that incorporating the risk score with current AJCC staging significantly improves the ability to stratify breast cancer patients with respect to DSS and OS. We recommend that the risk score be incorporated into the forthcoming revision of the AJCC staging system. Citation Format: Mittendorf EA, Vila J, Yi M, Chavez-MacGregor M, Chen RL, Giordano SH, Hunt KK. Evaluation of a risk score based on biologic factors to enhance prognostic stratification by the American Joint Committee on Cancer (AJCC) Staging System [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-17.

Background: Pathologic complete response (pCR) is associated with improved survival outcomes in patients with HER2-positive primary breast cancer. We developed a nomogram to predict the probability of pCR rates by using oestrogen receptor (ER) expression, progesterone receptor (PR) expression and HER2/CEP17 ratio as continuous variables. Methods: We retrospectively reviewed patients with stages I–III HER2-positive invasive breast cancer who had definitive surgery in 1999–2015 and received neoadjuvant systemic therapy (NST). Multivariate logistic regression models were applied to assess the effect of variables on pCR. A nomogram was built to estimate the probability of pCR. The discriminative ability was estimated by the concordance index (C-index). The accuracy was assessed graphically with a calibration curve. Results: A total of 793 patients were included in the analysis. Low ER expression (P

Background: Tumor biology is an important prognostic factor in breast cancer. The 8th edition AJCC pathologic prognostic stage incorporates biologic factors (grade, ER, PR, and HER2 status) along with anatomic staging to improve risk stratification. Additional staging models have been proposed including Bioscore and Risk Score. The Bioscore assigns a score of 0-7 based on anatomic stage, ER, HER2, and grade. The Risk Score assigns a score of 0-3 to each anatomic stage group, with 1 point assigned for ER-negative, HER2-negative, or grade 3 status. The objective of this study was to compare the performance of these models in a large, population-based cohort of breast cancer patients. Methods: The Surveillance, Epidemiology and End Results Program (SEER) database was used to identify primary stage I-IV breast cancer patients diagnosed in 2010. Patients were excluded for inflammatory carcinoma, neoadjuvant therapy, and missing data on receptors or tumor grade. 5-year disease specific survival (DSS) estimates were calculated using Cox regression for each staging model: AJCC anatomic stage, AJCC pathologic prognostic stage, Bioscore and Risk Score. Harrell concordance index (C-index) and Akaike Information Criterion (AIC) were used to compare each model in predicting DSS, with higher C-index and lower AIC indicating better predictive value and model fit. Results: 21,901 patients were included with a median age was 60 years. Median follow up was 52 months. All four staging models stratified DSS survival, with stepwise increases in hazard ratios and decrease in DSS for each increase in risk category (Table). The C-index of each model with biologic factors was higher than for anatomic stage, with the Risk Score having the highest C-index (0.832 for the anatomic stage; 0.856 for pathologic prognostic stage; 0.855 for Bioscore; and 0.864 for Risk Score). AIC was lowest for Risk Score (27315 for anatomic stage; 26874 for prognostic stage; 27120 for Bioscore; and 26753 for Risk Score), suggesting the best model fit for staging. Discussion: Staging models incorporating biologic factors perform better than anatomic staging alone. The Risk Score has the lowest AIC and may be the easiest to use as it simply assigns 1 point each for ER-negative, HER2-negative, and grade 3 tumors to each anatomic stage. In addition, the Risk Score has the added benefit of being the only staging system to stratify stage IV disease. We advocate for consideration of the Risk Score as an alternative to the pathologic prognostic stage for ease of use, optimal communication with patients and providers, and to standardize future clinical trials. Table. 5-yr estimates of DSS in 21,464 breast cancer patients in 4 models of breast cancer stagingAnatomic Stage5-yr DSSPrognostic Stage5-yr DSSBioscore5-yr DSSRisk Score5-yr DSSIA98.6IA98.7098.9IA098.9IB96.3IB93.7199.1199.2IIA94.5IIA90.1297.5297.1IIB92IIB84.2393.2392.8IIIA83.3IIIA80.5488.3IIA096.7IIIB73.2IIIB72.3570.2197.7IIIC68.6IIIC53.3656.2291.0IV38.8IV38.8732.2386.8IIB096.6194.7290.4380.4IIIA092.8190.0274.9365.2IIIB096.0180.3269.6353.9IIIC063.3178.0268.2339.7IV061.7147.5230.3310.8 Citation Format: Olga Kantor, Jiangong Niu, Hui Zhao, Sharon H Giordano, Kelly K Hunt, Tari A King, Elizabeth A Mittendorf, Mariana Chavez-MacGregor. Comparative analysis of proposed strategies for incorporating biologic factors into breast cancer staging [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-09.

// Reva K. Basho 1,* , Debora de Melo Gagliato 2,* , Naoto T. Ueno 2 , Chetna Wathoo 3 , Huiqin Chen 4 , Maryam Shariati 5 , Caimiao Wei 4,6 , Ricardo H. Alvarez 2,7 , Stacy L. Moulder 2 , Aysegul A. Sahin 8 , Sinchita Roy-Chowdhuri 8 , Mariana Chavez-MacGregor 2,9 , Jennifer K. Litton 2 , Vincent Valero 2 , Raja Luthra 8 , Jia Zeng 3 , Kenna R. Shaw 3 , John Mendelsohn 3,10 , Gordon B. Mills 3,11 , Debu Tripathy 2 and Funda Meric-Bernstam 3,5,12 1 Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 2 Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3 Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 4 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 5 Investigational Cancer Therapeutics (Phase I Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, USA 6 Pfizer, Inc, New York, NY, USA 7 The Cancer Treatment Centers of America, Chicago, IL, USA 8 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9 Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 10 Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 11 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 12 Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this work Correspondence to: Funda Meric-Bernstam, email: // Keywords : metastatic breast cancer, genomics, TP53, PIK3CA Received : April 06, 2016 Accepted : October 13, 2016 Published : October 28, 2016 Abstract BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene ( N = 126) and/or 46 or 50 gene ( N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected. RESULTS: Hotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients. CONCLUSIONS: Clinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.

Background The PI3K/AKT pathway is activated through PIK3CA or AKT1 mutations and PTEN loss in breast cancer. We conducted a phase II trial with an allosteric AKT inhibitor MK-2206 in patients with advanced breast cancer who had tumors with PIK3CA/AKT1 mutations and/or PTEN loss/mutation. Methods The primary endpoint was objective response rate (ORR). Secondary endpoints were 6-month progression-free survival (6 m PFS), predictive and pharmacodynamic markers, safety, and tolerability. Patients had pre-treatment and on-treatment biopsies as well as collection of peripheral blood mononuclear cells (PBMC) and platelet-rich plasma (PRP). Next-generation sequencing, immunohistochemistry, and reverse phase protein arrays (RPPA) were performed. Results Twenty-seven patients received MK-2206. Eighteen patients were enrolled into the PIK3CA/AKT1 mutation arm (cohort A): 13 had PIK3CA mutations, four had AKT1 mutations, and one had a PIK3CA mutation as well as PTEN loss. ORR and 6 m PFS were both 5.6% (1/18), with one patient with HR+ breast cancer and a PIK3CA E542K mutation experiencing a partial response (on treatment for 36 weeks). Nine patients were enrolled on the PTEN loss/mutation arm (cohort B). ORR was 0% and 6 m PFS was 11% (1/9), observed in a patient with triple-negative breast cancer and PTEN loss. The study was stopped early due to futility. The most common adverse events were fatigue (48%) and rash (44%). On pre-treatment biopsy, PIK3CA and AKT1 mutation status was concordant with archival tissue testing. However, two patients with PTEN loss based on archival testing had PTEN expression on the pre-treatment biopsy. MK-2206 treatment was associated with a significant decline in pAKT S473 and pAKT T308 and PI3K activation score in PBMC and PRPs, but not in tumor biopsies. By IHC, there was no significant decrease in median pAKT S473 or Ki-67 staining, but a drop was observed in both responders. Conclusions MK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations or PTEN loss. This may, in part, be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation, as well as tumor heterogeneity and evolution in markers such as PTEN conferring challenges in patient selection. Trial registration ClinicalTrials.gov, NCT01277757. Registered 13 January 2011. Electronic supplementary material The online version of this article (10.1186/s13058-019-1154-8) contains supplementary material, which is available to authorized users.

PURPOSE National hepatitis B virus (HBV) screening recommendations for patients with cancer anticipating systemic anticancer therapy range from universal screening to screening based on risk of HBV infection, cancer therapy–specific risk of HBV reactivation, or both. We conducted cost-effectiveness analyses to identify optimal HBV screening strategies. PATIENTS AND METHODS We constructed decision-analytic models to analyze three strategies (no screening, universal screening, and selective screening based on use of an HBV infection risk tool) for hypothetic cohorts of patients anticipating anticancer therapy at high or lower risk for HBV reactivation. Model parameters were drawn from previously published studies, the SEER-Medicare database, and other online resources. Outcomes included lifetime expected cost, quality-adjusted life expectancy, and incremental cost-effectiveness ratio, measured in US dollars required to gain an additional quality-adjusted life-year (QALY). RESULTS For patients at high reactivation risk, universal screening dominated (ie, was cheaper and more effective than) the other two strategies. Universal screening was associated with a gain in life expectancy of 0.01 QALY compared with no screening and cost $76.06 less than no screening and $4.34 less than selective screening. For those at lower reactivation risk, universal screening still dominated selective screening; however, the incremental cost-effectiveness ratio of the universal screening strategy compared with no screening was $186,917 per QALY gained. CONCLUSION Universal HBV screening is cost effective and cheaper for patients receiving anticancer therapy associated with a high reactivation risk. For patients receiving anticancer therapy associated with a lower reactivation risk, universal screening is not cost effective.

Many patients with clinically node-positive breast cancer receive neoadjuvant chemotherapy (NAC). Recent trials suggest the potential for limiting axillary surgery in patients who convert to pathologically node-negative disease. The authors developed a nomogram to predict axillary response to NAC in patients with cN1 disease that can assist clinicians in treatment planning. Patients with cT1–4N1M0 breast cancer who received NAC and underwent axillary lymph node dissection from 2001 through 2013 were identified (n = 584). Uni- and multivariate logistic regression analyses were performed to determine factors predictive of nodal conversion. A nomogram to predict the likelihood of nodal pathologic complete response (pCR) was constructed based on clinicopathologic variables and validated using an external dataset. Axillary pCR was achieved for 217 patients (37 %). Patients presenting with high nuclear grade [grade 3 vs. 1, odds ratio (OR) 13.4], human epidermal growth factor receptor 2-positive (OR 4.7), estrogen receptor (ER)-negative (OR 3.5), or progesterone receptor-negative (OR 4.3) tumors were more likely to achieve nodal pCR. These factors, together with clinically relevant factors including presence of multifocal/centric disease, clinical T stage, and extent of nodal disease seen on regional nodal ultrasound at diagnosis were used to create nomograms predicting nodal conversion. The discrimination of the nomogram using ER+ status (>1 % staining) versus ER− status [area under the curve (AUC) 78 %] was improved slightly using the percentage of ER staining (AUC 78.7 %). Both nomograms were validated using an external cohort. Nomograms incorporating routine clinicopathologic parameters can predict axillary pCR in node-positive patients receiving NAC and may help to inform treatment decisions.

Chemotherapy-induced cardiotoxicity, is a well-known and potentially serious complication strongly impacting the quality of life and overall survival of breast cancer patients. The current diagnostic approach to detect cardiac damage is the estimation of left ventricular ejection fraction by echocardiography. However, this approach exhibits less sensitivity toward early prediction of cardiomyopathy, not allowing for preventive strategies. Measurement of serum cardiac-specific biomarkers can be a valid diagnostic tool for identifying patients prone to developing cardiotoxocity and in whom closer cardiac monitoring and preventive strategies are pivotal. In this article, we review work done on biomarkers in recent years, with an emphasis on troponin and B-type natriuretic peptide, which are currently the most studied in this field. We also briefly discuss current and emerging imaging techniques for early detection of cardiomyopathy.

Background: Neoadjuvant chemotherapy (NACT) is an integral component for locally advanced and large operable breast cancer. The sequence of taxanes followed by anthracyclines has been the standard of care for almost 20 years. Eribulin (E) is a synthetic analogue of halichondrin B with distinct mechanism of action as microtubule dynamics inhibitor. The FDA approved E in 11/2010 for the treatment of patients (pts) with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Research Hypothesis: Sequential administration of eribulin followed by FAC/FEC-regimen, would have greater pathologic complete response (pCR) rate than sequential administration of paclitaxel followed by FAC/FEC-regimen as primary systemic therapy for woman with operable breast cancer. Methods: This is a phase II, randomized, single institution, open label study. Pts were randomized 1:1 to receive E (1.4 mg/m2 d1 and d8 q 21 days x 4) or paclitaxel (P) (80 mg/m2 weekly x12). Both arms received FAC/FEC regimen x 4 doses followed by surgery. Eligible pts were women age 18 or older, Karnosfky PS 80 – 100, histologically confirmed invasive breast cancer, clinical T2-T3, N0-3, M0, HER2-negative. Baseline LVEF of > 50% and normal hematology, liver and kidney laboratory function tests. Primary endpoint was pathologic complete response (pCR/RCB-0) assessed by residual cancer burden (RCB). [Symmans F, 2007]. This protocol (2012-0167) IRB of The University of Texas, MD Anderson Cancer Center. Results: A preplanned interim analysis aimed to validate trial assumption was conducted after treatment of 54 randomized pts. Between 8/2012 to 7/2014, 54 pts were randomized and 49 were evaluable for pCR(27 P arm and 22 E arm). Tumor response by RCB is shown in the table. pCR rates were 30% and 4.5% in the P and E arm, respectively. Table 1.ResponsePaclitaxel - FAC/FEC Arm (N=27)Eribulin - FAC/FEC Arm (N=22)RCB 0 (pCR)8 (30%)1 (4.5%)RCB I6 (22.2%)1 (4.5%)RCB II9 (33%)10 (45%)RCB III4 (14.8%)10 (45%) 53 pts were evaluable for toxicity. The combination was safe with mostly grade 1 and 2 toxicities in both arms. In the P arm grade 3 peripheral neuropathy and neutropenia was seen in 3% and 7%, respectively. In the E arm one patient died due to multiorgan failure during cycle 1. There was no other grade 3-5 toxicity. Biomarker analysis using CTCs by AdnaTest Breast were evaluated in 39 pts at baseline. 5/39 pts were positive for CTCs. 3 pts had transcripts for EpCAM, 1 for Muc-1 and another had both. 30 pts had an additional sample post therapy. 2 pts were positive for CTC at baseline as well as at follow up (FU) visit at 180 days. None of the samples showed CTC-EMT at baseline or at FU visits. Conclusions: The interim analysis demonstrated that E arm lead to significantly lower pCR/RCB1 rate compared to P arm. Ongoing biomarker analyses include TIL, hot spot mutation analysis (HSMA) and molecular inversion probes (MIP) will be presented at the time of the meeting. Clinical trial information: NCT01593020. Citation Format: Alvarez RH, Koenig KB, Ensor JE, Ibrahim NK, Chavez-MacGregor M, Litton JK, Schwartz Gomez JK, Cyriac A, Krishnamurty S, Caudle AS, Shaitelman SF, Whitman GJ, Booser DJ, Reuben JM, Valero V. A randomized phase II neoadjuvant (NACT) study of sequential eribulin followed by FAC/FEC-regimen compared to sequential paclitaxel followed by FAC/FEC-regimen in patients (pts) with operable breast cancer not overexpressing HER-2. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-04.

Background: Approximately 30% of TNBCs are characterized by microarray as claudin-low, mesenchymal or mesenchymal stem cell-like and, unlike basal TNBCs, these tumors frequently harbor aberrations in the PI3K/AKT/mTOR axis, raising the possibility of targeting this axis to enhance chemotherapy response. Assays to clinically identify mesenchymal TNBCs are under development, but published results confirm that up to 30% are metaplastic breast cancers (MpBCs), a chemo-refractory group of tumors that contain a mixture of epithelial and mesenchymal components, making them identifiable by microscopy. As such, MpBCs serve as surrogates of response for potential regimens to treat mesenchymal TNBC. Methods: Patients (pts) with advanced TNBC (N=64) were treated with liposomal doxorubicin (D), bevacizumab (A) and the mTOR inhibitors temsirolimus (T) or everolimus (E). D and A were administered IV on day 1 with T (IV on days 1, 8 and 15) or E (continuous daily oral administration) using 21 day cycles. Response was assessed every 6 weeks using RECIST. When available, archived tissue was evaluated for aberrations in the PI3K pathway using standard assays. Results: Fifty-two MpBC pts were treated with DAT (N=39) or DAE (N=13). Median age was 58 (range 37-79); median # of prior regimens for metastatic disease was 1 (range 0-5). The objective response rate (ORR) was 21% [complete response (CR)=4 (8%); partial response (PR)=7 (13%)] and 10 (19%) pts had stable disease (SD)≥6 months for a clinical benefit rate (CBR) of 40%. Tissue was available for testing in 43 pts and 32 (74%) had a PI3K pathway activating aberration (Table 1). Response According to PI3K Pathway AberrationPI3K Pathway AberrationN (%)CRPRSD≥6monthsCBRORRAny PI3K Pathway Aberration*32 (74)46444%31%PIK3CA Mutation19 (59)23447%26%p.H1047R12 (38)21350%25%p.E545K6 (19)02150%33%p.G1007R1 (3)010100%100%p.E545A1 (3)0000%0%p.H1047Y1 (3)0000%0%p.K111E1 (3)0000%0%p.E542K1 (3)0000%0%PIK3CA Amplification1 (3)010100%100%PTEN Mutation5 (16)0000%0%PTEN Loss5 (16)02040%40%AKT1 p.E17K Mutation2 (6)0000%0%AKT2 Amplification1 (3)100100%100%PIK3R1 Mutation2 (6)01050%50%NF2 Mutation1 (3)100100%100%No PI3K Pathway Aberration11 (26)00545%0%*Some tumors had >1 aberration detected PI3K pathway activation was associated with a significant improvement in ORR (31 vs 0%; P=0.043) but not CBR (44 vs 45%; P=1.000) or progression-free survival (median 5.1 vs 2.9 months; P=0.352). A pt with 5 year+ durable CR (on maintenance everolimus) had a mutation in NF2. To emphasize the importance of pt selection, it is notable that 12 pts with non-metaplastic TNBC were also treated with DAT, and only 1 pt had a response (CR/PR=1; SD≥6 months=0), for a CBR that was significantly worse than pts with MpBC (8 vs 40%; P=0.045). Conclusions: Using MpBC as a surrogate of response, DAT/DAE has significantly better activity in mesenchymal compared to non-selected TNBC. Response is enhanced in pts with PI3K pathway activation. DAT/DAE should be tested in non-metaplastic, mesenchymal TNBC once a diagnostic assay is available. Citation Format: Basho RK, Gilcrease M, Murthy RK, Helgason T, Booser DJ, Karp DD, Meric-Bernstam F, Wheler JJ, Valero V, Albarracin C, Litton J, Chavez-MacGregor M, Ibrahim NK, Murray JL, Koenig KB, Hong D, Subbiah V, Kurzrock R, Janku F, Moulder S. Targeting the PI3K/AKT/mTOR pathway for the treatment of mesenchymal triple-negative breast cancer (TNBC): Evidence of efficacy and proof of concept from a phase I trial with dose expansion of mTOR inhibition in combination with liposomal doxorubicin and bevacizumab. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-14-02.

Background: We previously described a novel breast cancer staging system, the CPS+EG score, which incorporates pretreatment clinical stage, post-treatment pathologic stage, estrogen receptor (ER) status and nuclear grade to create an ordinal scale that is predictive of disease-specific survival (DSS) after receipt of neoadjuvant chemotherapy. The prior work predated (1997-2005) routine use of trastuzumab for patients with HER2+ disease. The current study was undertaken to update the staging system with a more contemporary cohort of patients to include patients with HER2+ disease receiving trastuzumab. The impact of using 1% as the cutoff for ER-positivity was also assessed. Methods: A cohort of 2377 patients treated with neoadjuvant chemotherapy from 2005-2012 was identified. Clinicopathologic characteristics, treatment regimens and patient outcomes were recorded. Patient scores were computed using two versions of the CPS+EG staging system with ER status categorized as positive if >10% or if >1%. Fits of the Cox proportional hazards (PH) model for the two sets of prognostic scores were compared using the Akaike Information Criterion (AIC). HER2 status was then added to the model and the likelihood ratio test was used to determine the improvement in fit. Results: Median follow-up time was 4.2 years (range, 0.5 to 11.7). Five year DSS was 89% (95% CI: 87%-90%). This cohort validated our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than initial clinical or final pathologic stage alone (table). The AIC demonstrated that the CPS+EG model fits were nearly identical for ER status categorized using either cutoff, though the fit was slightly better for the >1% cutoff. There were 591 HER2+ patients included; all of them received trastuzumab-based chemotherapy. The improvement in the fit of the model when HER2 status was added was highly significant (p=0.00005) and incorporation of HER2 into the CPS+EG staging system by adding one additional point for HER2-negative status defined the bioscore (table) which again stratified patients with respect to prognosis. Conclusion: The current study demonstrates a novel bioscore that significantly improves a previously validated prognostic score in patients receiving neoadjuvant chemotherapy and allows the staging system to be applied to patients with HER2+ disease. We recommend that biologic markers and response to treatment be incorporated into the forthcoming revision of the AJCC staging system. Clinical Stage5-yr DSS (95%CI)Pathologic Stage5-yr DSS (95%CI)CPS+EG Score (1% cutoff for ER+)5-yr DSS (95%CI)Bioscore5-yr DSS (95%CI)0 097% (95-98%)098% (92-100%)097% (78-10)%)IA96% (75-99%)IA95% (92-97%)198% (96-99%)199% (95-100%)IIA96% (94-97%)IB90% (76-98%)294% (91-95%)297% (95-98%)IIB90% (87-92%)IIA91% (87-94%)387% (84-90%)393% (90-95%)IIIA85% (80-89%)IIB86% (81-90%)475% (69-80%)486% (82-89%)IIIB78% (70-85%)IIIA80% (75-84%)552% (40-63%)571% (64-77%)IIIC76% (70-81%)IIIB64% (42-80%)60648% (35-60%) IIIC64% (55-72%) 70 Citation Format: Mittendorf EA, Vila J, Tucker SL, Chavez-MacGregor M, Smith BD, Symmans WF, Sahin AA, Hortobagyi GN, Hunt KK. Bioscore: A novel staging system for breast cancer patients receiving neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-04.

Background: Everolimus (EVE; 10 mg) and exemestane (EXE; 25 mg) doublet therapy improved progression-free survival in women with hormone receptor-positive (HR+)/ HER2– advanced breast cancer (aBC; BOLERO-2), but was associated with significant mucositis as well as eventual disease progression. Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown clinical activity in combination with endocrine therapy and could potentially overcome phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor resistance by acting downstream of the PI3K pathway. Methods: In this ongoing Phase Ib/II study (NCT01857193), postmenopausal women with anastrozole- or letrozole-resistant HR+/HER2– aBC received escalating doses of the CDK4/6 inhibitor ribociclib (LEE011 [LEE]; once daily [QD], days 1–21 of 28-day cycles) with EVE (1–5 mg QD) and EXE (25 mg QD). Dose escalation was guided by a Bayesian logic regression model with overdose control principle and real-time pharmacokinetics. Pre-treatment tumor samples were sequenced by the Foundation Medicine platform. Here we report on the safety and efficacy of triplet therapy, and explore potential predictive biomarkers of response. Results: At the cut-off date March 2, 2015, 84 patients (pts) had been treated; here we present results from the 70 pts in the triplet arm treated with LEE (200–350 mg), EVE (most at 2.5 mg), and EXE. The median number of prior regimens was 5, and 18 (25.7%) pts had received prior PI3K/AKT/mTOR or CDK4/6 inhibitors for metastatic disease. Grade 3/4 treatment-related adverse events (AEs; ≥5% pts) were neutropenia (45.7%), leukopenia (8.6%), and thrombocytopenia (5.7%). Two (2.9%) pts discontinued due to AEs. Grade 3 dose-limiting toxicities were reported in 6 pts treated with LEE (300 mg) and EVE (2.5 mg): increased alanine aminotransferase/aspartate aminotransferase (2 pts), febrile neutropenia and hypophosphatemia (1 pt), oral mucositis (1 pt), rash and thrombocytopenia (1 pt), and thrombocytopenia with bleeding (1 pt). The recommended Phase II dose will be reported at the meeting. Among 55 pts evaluable for best overall response, there was 1 (1.8%) complete response (CR), 2 (3.6%) confirmed and 3 (5.5%) unconfirmed partial responses (PR), 7 (12.7%) non-CR, non-progressive disease (NCRNPD), and 26 (47.3%) stable disease (SD). Disease control rate (CR+PR+SD+NCRNPD) was 70.9%. One pt received treatment for ≥14 months, and 23 (32.9%) pts for ≥4 months. There was a trend towards longer duration of treatment in the CCND1 amplified group (n=10; median 166 days) than in the non-amplified group (n=22; median 60 days). A retrospective analysis of BOLERO-2 showed no differential effect of CCND1 amplification on PFS. Conclusions: Triplet combination of endocrine therapy with mTOR and CDK4/6 inhibition is feasible, permits lower dosing of EVE (resulting in better tolerability), and shows encouraging signs of clinical activity, including in some pts with prior exposure to PI3K/AKT/mTOR or CDK4/6 inhibitors. Duration of treatment was longer in pts with cyclin D amplification, possibly due to inclusion of a CDK4/6 inhibitor. These results suggest that that triplet therapy might be beneficial for pts who progress on doublets or who have cyclin D amplification. Citation Format: Bardia A, Modi S, Oliveira M, Campone M, Ma B, Dirix L, Weise A, Nardi L, Zhang V, Bhansali SG, Hewes B, Chavez-MacGregor M. Triplet therapy with ribociclib, everolimus, and exemestane in women with HR+/HER2– advanced breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-01.

No studies have examined the impact of the interval from conclusion of neoadjuvant chemotherapy to surgery in breast cancer patients. This study was undertaken to investigate the relationship between time interval from neoadjuvant chemotherapy to surgery and survival outcomes.Breast cancer patients diagnosed with stage I-III disease who received neoadjuvant chemotherapy June 1995 to April 2007 were identified. The effect of neoadjuvant chemotherapy to surgery interval, defined as ≤4, 4-6, or6 weeks, on survival outcomes was examined. Descriptive statistics and Cox proportional hazards models were used.A total of 1101 patients were identified. Median time to surgery was 33 (range 8-159) days; 335 patients (30.4 %) had surgery within 4 weeks of their last dose of neoadjuvant chemotherapy, 524 (47.6 %) within 4-6 weeks, and 242 (22.0 %) after more than 6 weeks. Median follow-up was 94 (range 3-178) months. The 5-year overall survival (OS) estimates were 79, 87, and 81 % in patients who underwent surgery ≤4, 4-6, and6 weeks after neoadjuvant chemotherapy, respectively (p = 0.03). The three groups did not differ in 5-year recurrence-free survival (RFS) or locoregional recurrence-free survival (LRFS). In multivariable analysis, compared with an interval of ≤4 weeks, patients who underwent surgery at 4-6 or6 weeks had equivalent OS, LRFS, and RFS; a sensitivity analysis suggested worse OS in patients who underwent surgery at8 weeks.Patients with neoadjuvant chemotherapy to surgery intervals of up to 8 weeks had equivalent OS, RFS, and LRFS.

Background. The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER2+ locally advanced breast cancer (LABC). Patients and Methods. The present retrospective study included 555 patients with HER2+ LABC who had undergone NST and definitive surgery (1999–2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 3+ and/or HER2 FISH ratio of ≥2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio, either as a continuous variable or with a cutoff of ≥7.0, would predict for pCR (no invasive disease in the breast and no tumor in the ipsilateral axillary lymph nodes), RFS, and/or OS. Results. The pCR group's median HER2 FISH ratio was significantly higher than that of the non-pCR group (6.4 vs. 5.2; p = .003). The logistic regression model demonstrated that the independent predictors of pCR included a high HER2 FISH ratio as a continuous variable (p = .04). The multicovariate Cox proportional hazard model showed that a high HER2 FISH ratio (with a cutoff of ≥7.0 or as a continuous variable) was a significant prognostic indicator of longer RFS time (p = .047 and p = .04, respectively). Similarly, a high HER2 FISH ratio of ≥7.0 was associated with longer OS (p = .06). Conclusion. A high HER2 FISH ratio is a predictor of pCR in patients with HER2+ LABC who receive NST-T.