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IMPORTANCE: Patients who are uninsured and belong to racial and ethnic minority groups or have low socioeconomic status have suboptimal access to health care, likely affecting outcomes. The association of the Affordable Care Act’s Medicaid expansion with survival among patients with metastatic breast cancer is unknown. OBJECTIVE: To examine the association between Medicaid expansion and mortality disparity among patients with de novo stage IV breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, population-based study of survival using Cox proportional hazards regression and difference-in-difference (DID) analysis of data from the National Cancer Database and patients diagnosed as having de novo stage IV breast cancer between January 1, 2010, and December 31, 2016, residing in states that underwent Medicaid expansion on January 1, 2014. The preexpansion period was January 1, 2010, to December 31, 2013; the postexpansion period was January 1, 2014, to December 31, 2016. Data were analyzed between September 4, 2020, and November 16, 2021. EXPOSURES: Comparison of survival improvement between patients of racial and ethnic minority groups and White patients in the preexpansion and postexpansion periods. Because of small numbers in the specific racial and ethnic minority groups, these patients were combined into 1 category for comparisons. MAIN OUTCOMES AND MEASURES: Overall survival (OS) and 2-year mortality rate. RESULTS: Among 9322 patients included (mean [SD] age, 55 [7] years), 5077 were diagnosed in the preexpansion and 4245 in the postexpansion period. The racial and ethnic minority group comprised 2545 (27.3%), which included 500 (5.4%) Hispanic (any race), 1515 (16.3%) non-Hispanic Black, and 530 (5.7%) non-Hispanic other including 25 (0.3%) American Indian or Alaska Native, 357 (3.8%) Asian or Pacific Islander, and 148 (1.6%) unknown, and 6777 (72.7%) were in the White patient group. In the preexpansion period, White patients had increased OS compared with patients of racial and ethnic minority groups (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.10-1.35); this difference was not observed in the postexpansion period (aHR, 0.96; 95% CI, 0.86-1.08). A reduction in 2-year mortality was observed between the preexpansion and postexpansion periods (32.2% vs 26.0%). The adjusted 2-year mortality decreased from 40.6% to 36.3% among White patients and from 45.6% to 35.8% among patients of racial and ethnic minority groups (adjusted DID, −5.5%; 95% CI, −9.5 to −1.6; P = .006). Among patients in the lowest income quartile (n = 1510), patients of racial and ethnic minority groups had an increased risk of death in the preexpansion period (aHR, 1.28; 95% CI, 1.01-1.61) but lower risk in the postexpansion period (aHR, 0.75; 95% CI, 0.59-0.95). In this subset of patients, those of racial and ethnic minority groups had a greater reduction in 2-year mortality compared with White patients (adjusted DID, −12.8%; 95% CI, −22.2 to −3.5; P = .007). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, survival differences observed between patients of racial and ethnic minority groups and White patients in the preexpansion period were no longer present in the postexpansion period. A greater reduction in 2-year mortality was observed among patients of racial and ethnic minority groups compared with White patients. These results suggest that policies aimed at improving equity and increasing access to health care may reduce racial and ethnic disparities in breast cancer outcomes.

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.

PDF - 160KB, Supplementary Figure 1 -Histograms of BUM model to the P-values from the ANOVA test of race/ethnicity by breast cancer subtype in 177 proteins. Supplementary Figure 2 - Histograms of BUM model to the P-values from the ANOVA test of race/ethnicity by breast cancer subtype in 16,438 probe sets. Supplementary Figure 3 - Unsupervised clustering of the significant 384 probe sets with FDR

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Background: Differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype.Methods: Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. Standard statistical methods, BRB-Array tools, and Ingenuity Pathways software packages were used to analyze the data.Results: Median age was 50 years in both the cohorts. In the RPPA cohort, 54.5% of the tumors were hormone receptor–positive (HR-positive), 20.7% HER2-positive, and 24.71% triple-negative (TNBC). One hundred and forty-seven (57.6%), 47 (18.43%), and 46 (18.1%) of the patients were White, Hispanic, and Black, respectively. Unsupervised hierarchical clustering of the protein expression data showed no distinct clusters by race (P values were 0.492, 0.489, and 0.494 for the HR-positive, HER2-positive, and TNBC tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR-positive, 16.5% HER2-positive, and 29.3% TNBC. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were White, Hispanic, and Black, respectively. No probe set with a false discovery rate (FDR) of Conclusions: We did not detect a significant variation in RNA or protein expression comparing different race/ethnicity groups of women with breast cancer.Impact: More research on the complex network of factors that result in outcomes differences among race/ethnicities is needed. Cancer Epidemiol Biomarkers Prev; 23(2); 316–23. ©2013 AACR.

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Ashley J Housten,1 Catalina Malinowski,2 Edna Paredes,3 Cassandra L Harris,3 Lorna H McNeill,3 Mariana Chavez-MacGregor2,4 1Division of Public Health Sciences, Washington University School of Medicine, St Louis, MO, USA; 2Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Mariana Chavez-MacGregor, 1400 Pressler St Unit 1444, Houston, TX, 77030, USA, Tel +1 713 563 0020, Email MChavez1@mdanderson.orgPurpose: (Neo) adjuvant chemotherapy decreases the risk of recurrence and improves overall survival among breast cancer patients; however, delays in chemotherapy initiation are associated with adverse health outcomes. The causes of delay are complex and include interrelated social, economic, cultural, environmental, and health system factors. Project Start was a qualitative study designed to assess and identify the multilevel factors contributing to the barriers and facilitators of initiating chemotherapy.Patients and Methods: Women diagnosed with primary invasive breast cancer who experienced ≥ 60 day delay in (neo) adjuvant chemotherapy initiation were included. Participants completed semi-structured interviews exploring barriers and facilitators to starting chemotherapy. Interviews were transcribed and coded to identify themes using the Sort and Sift, Think and Shift analytic approach. This analysis included thorough examination of the data by advancing through iterative analytic phases to identify core topics within and across transcripts.Results: We enrolled (N=22) participants with median age at diagnosis 53.5 years (range 27– 70) who identified as Latina (n=8), Black (n=5), and non-Latina White (n=9). Participants described a common chemotherapy initiation process reflecting their unique needs as they transitioned through four stages: 1) receiving diagnosis and treatment recommendations; 2) processing treatment options; 3) “Flipping the Switch”; and 4) activating treatment and engaging in care. Limited explicit insight into their chemotherapy delay was expressed. Engagement across the self-, family-, community-, and medical-realms revealed interlinked and pivotal sources of support that helped participants navigate toward initiating chemotherapy. Specifically, the overarching themes included logistical, emotional, financial, and social sources of support and the relationship of these sources of support to participants’ perceived self-efficacy to move toward initiating treatment.Conclusion: Activating women to be engaged in the treatment process across multiple levels appeared to facilitate initiating chemotherapy. Multilevel interventions that engage the patient, family, community, and medical team may support the initiation of timely chemotherapy.Keywords: breast cancer, care delivery, chemotherapy, treatment delay, oncology, qualitative, patient perspectives

Background Medicaid expansion under the Affordable Care Act extends eligibility for participating states and has been associated with improved outcomes by facilitating access to care. Delayed initiation of adjuvant chemotherapy is associated with worse outcomes among patients with early-stage breast cancer (BC). The impact of Medicaid expansion in narrowing delays by race and ethnicity has not been studied, to our knowledge. Methods This was a population-based study using the National Cancer Database. Patients diagnosed with primary early-stage BC between 2007 and 2017 residing in states that underwent Medicaid expansion in January 2014 were included. Time to chemotherapy initiation and proportion of patients experiencing chemotherapy delays (>60 days) were evaluated using difference-in-difference and Cox proportional hazards models in preexpansion and postexpansion periods according to race and ethnicity. Results A total 100 643 patients were included (63 313 preexpansion and 37 330 postexpansion). After Medicaid expansion, the proportion of patients experiencing chemotherapy initiation delay decreased from 23.4% to 19.4%. The absolute decrease was 3.2, 5.3, 6.4, and 4.8 percentage points (ppt) for Black, Hispanic, White, and Other patients. Compared with White patients, statistically significant adjusted difference-in-differences were observed for Black (−2.1 ppt, 95% confidence interval [CI] = −3.7% to −0.5%) and Hispanic patients (−3.2 ppt, 95% CI = −5.6% to −0.9%). Statistically significant reductions in time to chemotherapy between expansion periods were observed among White patients (adjusted hazard ratio = .11, 95% CI = 1.09 to 1.12) and those belonging to racialized groups (adjusted hazard ratio = 1.14, 95% CI = 1.11 to 1.17). Conclusions Among patients with early-stage BC, Medicaid expansion was associated with a reduction in racial disparities by decreasing the gap in the proportion of Black and Hispanic patients experiencing delays in adjuvant chemotherapy initiation.

ObjectivesWe compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes.MethodsThis retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE using multivariable logistic regression. In addition, within SLE cases, we examined factors associated with COVID-19 related outcomes, including disease activity and SLE therapy.ResultsWe included 687 patients matched with 6870 controls. Unadjusted rates of outcomes for patients with SLE were significantly worse than for matched controls including mortality (3.6% vs 1.8%), mechanical ventilation (6% vs 2.5%) and hospitalisation (31% vs 17.7%) (all pConclusionPatients with SLE had increased risk of severe COVID-19-related outcomes compared with matched controls. Patients with severe SLE disease activity or prior use of corticosteroids experienced worse outcomes.

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. 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 retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .

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.

Catalina Malinowski,1 Edna Paredes,2 Ashley J Housten,3 Mariana Chavez-MacGregor2,4 1Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Division of Public Health Sciences, Washington University School of Medicine, St Louis, MO, USA; 4Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Mariana Chavez-MacGregor, 1400 Pressler St Unit 1444, Houston, TX, 77030, USA, Tel +1 713 563 0020, Email MChavez1@mdanderson.orgPurpose: Although the association between delays in (neo)adjuvant chemotherapy initiation and adverse outcomes is well-documented, patient perspective regarding the lived experience among those with breast cancer delay is sparse. Project Start was a qualitative study designed to assess and identify the multilevel factors contributing to the barriers and facilitators of initiating chemotherapy. This report explores specific responses where patients with breast cancer provide insight and advice for newly diagnosed women on preparing for chemotherapy initiation and informs potential interventions to facilitate timely chemotherapy initiation.Patients and Methods: Women diagnosed with primary invasive breast cancer who experienced a ≥ 60-day delay in (neo)adjuvant chemotherapy initiation were included. Participants completed semi-structured interviews exploring barriers and facilitators to starting chemotherapy. Interviews were transcribed and coded to identify themes.Results: We enrolled (N = 22) participants with a median age at diagnosis of 53.5 years (range 27– 70) who identified as Latina (n = 8), Black (n = 5), and non-Latina White (n = 9). Our participants indicated that engaging their medical teams and seeking support earlier were essential to initiate their treatment journeys. They emphasized being proactive and thorough in all aspects of their journey, particularly in processing medical recommendations, communicating with medical personnel, and identifying areas of need. Although explicit insight into chemotherapy delay was rare, participants expressed the importance of beginning treatment promptly. They shared advice on acquiring support (eg, financial, emotional, logistical, spiritual) and suggested connecting with breast cancer survivors to overcome the complex challenges of cancer care.Conclusion: Patient perspectives regarding barriers and treatment facilitators help provide insight into the lived experience of cancer care journeys that can inform interventions to improve patient support and outcomes. We are using these results to develop a pilot study to test the acceptability and feasibility of a culturally tailored patient navigation intervention to increase self-efficacy and avoid treatment delays.Keywords: breast cancer, care delivery, chemotherapy, treatment delay, oncology, qualitative, patient perspectives

Background: (Neo) Adjuvant chemotherapy decreases the risk of recurrence and improves overall survival among breast cancer patients, however, delays in chemotherapy initiation are associated with adverse outcomes. While the determinants of such delays are not clearly understood, delays are more likely to occur in those: with additional comorbidities, belonging to a low social economic status, without a partner, enrolled in public health insurance, or who identify as Latino/Hispanic or Black/African Americans. The causes of disparities in the delivery of care among breast cancer patients are complex and include interrelated social, economic, cultural, environmental, and health system factors. The goal of Project Start was to conduct a qualitative investigation to assess and identify the multilevel factors contributing to the barriers and facilitators of initiating chemotherapy in the context of breast cancer treatment. Methods: We enrolled English or Spanish speaking women, ≥18 years, diagnosed with primary invasive breast cancer who experienced a ≥ 60 days delay to chemotherapy initiation, whether adjuvant or neoadjuvant (determined from the date of surgery or the date of histopathologic diagnosis). Participants were identified through electronic medical record review and approached in clinic to participate. Semi-structured interviews were conducted in-person or over the phone to explore participants’ perceptions about individual, community, and system level barriers and facilitators contributing to starting chemotherapy. Interviews were audio-recorded, transcribed verbatim, and coded using the Sort and Sift, Think and Shift qualitative approach to identify concepts and topics within and across transcripts. Participants completed brief questionnaires collecting sociodemographic characteristics, health literacy and numeracy, physician trust, and social support to supplement the qualitative data. Quantitative data were summarized using descriptive statistics. Results: Seventeen participants completed semi-structured interviews and questionnaires (mean age 49.9 years; range 30-70 years). Participants identified as: Latina (n=7); Black (n=2); and non-Latina White (n=8). Most completed interviews in English (n=15) and over half had lower educational attainment (i.e., middle school, high school, associate’s degree; n=10). While the interview included questions addressing chemotherapy delays, explicit insight into chemotherapy delay was rare among participants. When discussing their process to chemotherapy, participants described barriers and facilitators at the patient, family, medical, and community levels contributing to their timeline to start chemotherapy. At the patient level, participants discussed their fear and anxiety, the command over their diagnosis, and the importance of playing an active role in treatment. Within the family realm, participants described their family roles (e.g., caregiving, income), treatment costs, and the need for emotional support (e.g., not shutting family members out). Participants sought out and relied heavily on support from their communities (e.g., churches, other patients, survivors). Finally, patients described their reliance on the medical team for information, the trust needed to navigate their treatment process, and the challenge of managing information associated with their treatment. Conclusions: Women expressed the importance of managing individual stressors, family roles and support, medical information, and community support. Activating women to be engaged in the treatment process at multiple levels appeared to facilitate initiating chemotherapy. Multilevel interventions that engage the patient, family, medical team, and community may provide the supports to enable the initiation of timely chemotherapy. Citation Format: Ashley J. Housten, Edna Paredes, Cassandra L. Harris, Mariana Chavez-MacGregor. Why do women experience a delay to chemotherapy? A qualitative analysis [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 PS7-75.

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.

BACKGROUND: Delays in adjuvant chemotherapy initiation have a detrimental effect in outcomes and are more frequently seen among racial/ethnic minorities, uninsured patients and those with low socioeconomic status. A provision in the Affordable Care Act called for expansion of Medicaid eligibility in order to cover more low-income Americans. In this study we evaluate the impact of Medicaid expansion on racial disparities in time to adjuvant chemotherapy administration in a large cohort of BC patients.METHODS: Women (aged 40-64) diagnosed with primary invasive BC (stage I-III) between 01/01/2007 and 12/31/2016 were identified in the National Cancer Database. All patients underwent surgery as initial treatment modality and received adjuvant chemotherapy within 6 months of surgery. Chemotherapy delay was defined as >60 days from surgery to the first dose of chemotherapy. The cohort was limited to those residing in states that underwent Medicaid expansion in 2014 (KY, NV, CO, OR, NM, WV, AR, RI, AZ, MD, MA, ND, OH, IA, IL, VT, HI, NY, DE). For comparison purposes, 2007-2013 was considered the pre-expansion period and 2014-2016 the post-expansion period. We calculated difference-in-difference (DID) estimates using multivariable linear regression models. Results are presented as adjusted differences (in % points) between race/ethnicity groups in the pre and post-expansion periods, and as adjusted DID with 95% CI. A negative DID estimate indicates that Medicaid expansion reduces the racial/ethnic disparity in chemotherapy administration delay. The parallel trend assumption was tested. Variables in the final model included age, comorbidities, BC subtype, insurance status, distance to treatment facility, region, education, household income, facility type and facility case volume. RESULTS: 105,385 patients were included (median age 53), of them 75,663 (71.8%) were diagnosed in the pre- and 29,722 (28.2%) in the post-expansion period. 77.5% of the patients were White, 11.7% Black and 4.9% Hispanic. The proportion of patients experiencing chemotherapy initiation delays was greater among Blacks and Hispanics in both study periods compared to Whites. The proportion of chemotherapy delays decreased for all races between the pre and the post-expansion period. We observed a statistically significant decrease in the chemotherapy initiation racial disparity. The adjusted DID was -2% (95%CI -3.8 to -0.3, P=0.02) between Whites and Blacks was and -3% (95%CI -5.5 to -0.5, P=0.02) between Whites and Hispanics. In a subgroup analysis among 10,777 Medicaid patients the parallel trend assumption was not valid, therefore we estimated the DID between Whites and Blacks using a propensity-score based weight sample, identifying a reduction in the racial disparity of even greater magnitude (DID -9.1% [-14.4 to -3.8, P CONCLUSIONS: We demonstrate that Medicaid expansion reduced racial disparities by decreasing the proportion of Blacks and Hispanics experiencing delays in adjuvant chemotherapy initiation and decreasing the gap that exists when compared to Whites. These important results highlight the positive impact of policies aimed at improving equity and increasing access to health care. Pre-ExpansionPost-ExpansionRaceNAdjusted Rate of Delayed Chemo > 60 daysAdjusted Difference Between White Race (% points)NAdjusted Rate of Delayed Chemo > 60 daysAdjusted Difference Between White Race, (%points)Adjusted DID (95% CI), Percentage PointsPWhite5930527.202232524.20RefRefBlack856036.18.9372031.16.9-2.0 (-3.8 to -0.3)0.02Hispanic343232.35.1170426.32.1-3.0 (-5.5 to -0.5)0.02 Citation Format: Mariana Chavez-MacGregor, Xiudong Lei, Hui Zhao, Tina Shih, Sharon H Giordano. Impact of Medicaid expansion on racial disparities in time to adjuvant chemotherapy administration among breast cancer (BC) patients [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 SS1-10.

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.

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.

PURPOSE: The increased number and expanded utilization of biosimilars raise important considerations for their safe and appropriate use in oncology practice. This report provides an update on currently approved oncology biosimilars and identifies current knowledge gaps in the management of patients with cancer. METHODS: An Expert Panel was convened to review the medical literature and to provide a practical summary of currently approved biosimilar therapeutics for cancer treatment or supportive care in the United States. RESULTS: A total of 17 cancer or cancer-related biosimilar products have been approved by the US Food and Drug Administration since 2015. Despite years of clinical experience with oncology biosimilars, variance in their use persists. ASCO supports that biosimilars and reference products are considered equally efficacious for the purpose of inclusion in ASCO clinical practice guideline recommendations. CONCLUSION: The use of biosimilars might provide competitive, lower-cost alternatives to biologics used in cancer care, and specific mention in ASCO guidelines and other evidence products is supported where appropriate.

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.

OBJECTIVE: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins < 2 mm. METHODS: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A univariate analysis revealed that age

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.

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.

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.

BackgroundTumor cells with a mesenchymal phenotype and/or cancer stem-like cells (CSCs) are known to contribute to metastasis and drug resistance. Circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) and CTCs reflecting a dedifferentiated CSC phenotype may not be detected using only an anti-EpCAM antibody to capture them. We used an antibody-independent CTC enrichment platform, ApoStream®, which does not rely on any antibody, including anti-EpCAM, to capture EMT- and CSC-CTCs in breast cancer patients who received neoadjuvant chemotherapy and correlated them to pathological complete response (pCR).MethodsBlood samples from newly diagnosed breast cancer patients were prospectively collected before neoadjuvant chemotherapy (T0), after chemotherapy but before surgery (T1), and after surgery (T2) and processed using ApoStream. CTCs detected were stained with additional markers to define 3 CTC subsets with the following phenotypes: epithelial CTCs (CK+, EpCAM+ or E-cadherin+), EMT-CTCs (β-catenin+ or vimentin+), and CSC-CTCs (CD44+ and CD24low).ResultsWe enrolled 55 patients, 47 of which had data for analysis. EMT-CTCs were detected in 57%, 62%, and 72% and CSC-CTCs in 9%, 22%, and 19% at the T0, T1, and T2 time points, respectively. Counts of epithelial (P = 0.225) and EMT (P = 0.522) phenotypes of CTCs at T0 did not significantly predict pCR. Moreover, no correlation between CTC count change and pCR was demonstrated.ConclusionsApoStream was successful in detecting EMT-CTCs among patients after neoadjuvant chemotherapy. However, EMT-/CSC-CTC counts did not correlate with pCR. Due to the small sample size and heterogeneity of this patient population, further study in a larger cohort of molecularly homogeneous patients is warranted.