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The decision in Dobbs v Jackson Women's Health Organization overturned federal protections for abortion rights, making way for states to enact abortion bans with or without exceptions for the health or life of the pregnant patient. Patient care across many areas of medicine including oncology continues to be affected. Although the change in the legal landscape is widely felt, the core ethical considerations for physicians do not change because of restrictions on the practice of medicine. ASCO offers this guidance to assist US oncologists and institutions who must balance limitations with established ethical duties. This paper articulates principles for cancer care and pregnancy, offers a framework for ethical reflection and action for oncologists who care for pregnant patients, and makes recommendations for individual and institutional action to support evidence-based, patient-centered care in the United States where abortion is illegal or access is limited.

PURPOSE Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. METHODS Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to RESULTS At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). CONCLUSION Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

PURPOSE: To investigate implicit bias (IB) in the peer review process across ASCO and Conquer Cancer Foundation and to propose potential mitigation strategies. MATERIALS AND METHODS: We, ASCO Working Group on Implicit Bias, selected four data sources: (1) literature search [(a) defining IB in peer review, (b) evidence of IB in peer review, and (c) strategies to mitigate IB]; (2) created and analyzed an ASCO database for sex, race, and institutional affiliation regarding peer review success; (3) constructed and conducted qualitative interviews of key stakeholders within the ASCO board, publications, and grants committee, on experience with IB within ASCO; and (4) constructed, delivered, and analyzed results of member survey on perception of IB within ASCO. RESULTS: Historically uncommon, PubMed articles on IB in peer review subsequently increased exponentially in the past 2 decades. Qualitative interviews of ASCO key stakeholders reveal that system changes and IB training were priorities. The committee member survey reported that their peer review decisions could be affected by IB and that mitigating IB should be a priority. Most reported having never been trained on IB. Available data from ASCO database support stakeholder findings, suggesting that there exists a disproportionate representation of males and better-known institutions among both reviewer positions and awardees. Ethnicity/race data were insufficiently reported. Limited data on interventions/strategies to mitigate IB in the peer-reviewed literature suggest that there are feasible processes for grants, program committees, and journals. CONCLUSION: Limited data reveal that the peer review process at ASCO is not exempt from IB and suggest association with sex and institutional affiliation. Working Group on Implicit Bias recommends three actions to mitigate IB within peer review: (1) create awareness and a culture of inclusivity, (2) create systems to reduce IB, and (3) collect data for ongoing analysis.

ImportanceWhether racial and ethnic disparities in locoregional recurrence (LRR) exist among patients with similar access to care treated in randomized clinical trials is unknown.ObjectiveTo examine racial and ethnic differences in LRR among patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])–negative, node-negative breast cancer enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx).Design, Setting, and ParticipantsThis unplanned retrospective post hoc analysis examined a prospective multicenter clinical trial population of women with breast cancer enrolled between 2006 and 2010, with 9 years of follow-up. The TAILORx investigators randomized patients to treatment based on their Oncotype DX recurrence score, including endocrine therapy alone (recurrence score 25). Patients with unknown race and ethnicity or lack of follow-up were excluded from this analysis. Data analysis was performed between December 2021 and March 2022.Main Outcome and MeasuresLocoregional recurrence was defined as ipsilateral in breast, skin, chest wall, or regional nodal recurrence without concurrent distant recurrence, and was stratified by racial and ethnic group. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards regression models were used for survival analyses.ResultsOf the 10 273 women enrolled in TAILORx, this analysis included 9369 with T1-2N0 HR-positive, ERBB2-negative breast cancer. Of these patients, 428 (4.6%) were Asian, 886 (9.4%) were Hispanic, 676 (7.2%) were non-Hispanic Black (hereinafter Black), and 7406 (78.8%) were non-Hispanic White (hereinafter White). Assigned treatment receipt was high, with a 9.3% (n = 870) crossover of treatment groups and a median endocrine therapy duration of longer than 60 months, ranging from 61.1 to 65.9 months, across racial and ethnic groups. A total of 6818 patients (72.6%) received radiation (6474 [96.1%] after breast-conserving surgery and 344 [13.0%] after mastectomy). At a median follow-up of 94.8 months (range, 1-138 months), 8-year LRR rates were 3.6% (95% CI, 1.6%-5.6%) in Asian patients, 3.9% (95% CI, 2.2%-5.4%) in Black patients, 3.1% in Hispanic patients (95% CI, 1.7%-4.5%), and 1.8% (95% CI, 1.5%-2.3%) in White patients (P Conclusions and RelevanceIn this post hoc analysis, racial and ethnic differences in LRR were observed among patients with T1-2N0 HR-positive, ERBB2-negative breast cancer despite high rates of treatment receipt in this clinical trial population, with the highest LRR rates in Asian and Black patients. Further study is needed to understand whether failure to rescue after LRR may contribute to racial disparities in breast cancer mortality.Trial RegistrationClinicalTrials.gov Identifier: NCT00310180

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.

This study sought to determine the impact of pregnancy or assisted reproductive technologies (ART) on breast-cancer-specific survival among breast cancer survivors.The authors performed a cohort study using a novel data linkage from the California Cancer Registry, the California birth cohort, and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System data sets. They performed risk-set matching in women with stages I-III breast cancer diagnosed between 2000 and 2012. For each pregnant woman, comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics were matched at the time of pregnancy. After matching, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of pregnancy with breast-cancer-specific survival. We repeated these analyses for women who received ART.Among 30,021 women with breast cancer, 553 had a pregnancy and 189 attempted at least one cycle of ART. In Cox proportional hazards modeling, the pregnancy group had a higher 5-year disease-specific survival rate; 95.6% in the pregnancy group and 90.6% in the nonpregnant group (HR, 0.43; 95% CI, 0.24-0.77). In women with hormone receptor-positive cancer, we found similar results (HR, 0.43; 95% CI, 0.2-0.91). In the ART analysis, there was no difference in survival between groups; the 5-year disease-specific survival rate was 96.9% in the ART group and 94.1% in the non-ART group (HR, 0.44; 95% CI, 0.17-1.13).Pregnancy and ART are not associated with worse survival in women with breast cancer.We sought to determine the impact of pregnancy or assisted reproductive technologies (ART) among breast cancer survivors. We performed a study of 30,021 women by linking available data from California and the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. For each pregnant woman, we matched at the time of pregnancy comparable women who were not pregnant at that point but were otherwise similar based on observed characteristics. We repeated these analyses for women who received ART. We found that pregnancy and ART were not associated with worse survival.

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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XLSX - 25KB, RPPA Antibody List.

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.

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

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 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

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: 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: (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 There is ongoing debate regarding the optimal timing of contralateral prophylactic mastectomy fueled by concern that performing it at the time of the mastectomy for the index breast cancer may delay adjuvant therapy. The study objective was to examine the effect of simultaneous contralateral prophylactic mastectomy with immediate breast reconstruction on the complication rate and adjuvant therapy timing. METHODS A retrospective study was conducted of consecutive patients who underwent contralateral prophylactic mastectomy with immediate breast reconstruction and received adjuvant therapy over a 6-year period. Demographic, treatment, and outcomes data were collected, and relationships between multiple variables and outcomes were evaluated. RESULTS Of 241 patients (482 breasts) included, 186 (372 breasts) underwent simultaneous index breast mastectomy and contralateral prophylactic mastectomy with immediate breast reconstruction followed by adjuvant therapy (immediate group), and 55 (110 breasts) underwent index mastectomy, then adjuvant therapy, followed by delayed contralateral prophylactic mastectomy with immediate breast reconstruction (delayed group). Demographics were similar, although breast cancer stage (p < 0.001), tumor category (p = 0.0072), and nodal category (p < 0.001) were significantly higher in the delayed group. In the immediate group, complications before adjuvant therapy occurred in 31 patients (16.7 percent), and in six patients (3.2 percent) complications occurred only in the contralateral prophylactic mastectomy breast; delay to adjuvant therapy occurred in 11 patients (5.9 percent), in four (2.2 percent) of whom the contralateral prophylactic mastectomy breast was responsible for the delay. CONCLUSIONS Contralateral prophylactic mastectomy with immediate breast reconstruction can be performed safely at the time of the index mastectomy in carefully selected patients. These findings will engage patients seeking contralateral prophylactic mastectomy in shared decision-making regarding optimal timing with respect to the risks and benefits. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

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.

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.