Palbociclib in adults aged 70 years and older with advanced breast cancer: A phase 2 multicenter trial (Alliance A171601).

INTRODUCTION: Palbociclib is a widely used treatment for advanced breast cancer in older adults. However, the existing evidence regarding its safety and tolerability in this age group is inconsistent and limited to retrospective subgroup or pooled analyses. MATERIALS AND METHODS: We conducted a prospective single-arm multicenter phase 2 study to evaluate the safety and tolerability of palbociclib in participants aged 70 years or older with advanced hormone receptor-positive breast cancer. Participants were given palbociclib in combination with their physician's choice of endocrine therapy (letrozole or fulvestrant). The primary endpoint was the incidence of grade 3+ adverse events (AEs) by six months. Secondary endpoints included AE-related dose delays, dose reductions, early discontinuations, and hospitalizations. Additionally, we compared these endpoints by age groups (70-74 and ≥ 75 years). RESULTS: Of the 90 participants (median age 74 years [70-87]) enrolled, 75.6% (95% confidence interval [CI], 65.4-84.0) had grade 3+ AEs by six months. The most frequent grade 3+ AEs were neutropenia (61%), fatigue (4%), and nausea (3%). Febrile neutropenia was uncommon (1.1%). Due to AEs, 36% had dose delays, 34% had dose reductions, 10% had early discontinuations, and 10% had hospitalizations. Compared to those aged 70-74 years, participants aged ≥75 years had higher rates of early discontinuations (5.9% vs 15.9%, a difference of 9.5% [95% CI 3.5%-22.5%]). DISCUSSION: Palbociclib has an overall favorable safety profile in adults aged ≥70 with advanced breast cancer. However, adults ≥75 years had a trend toward higher rates of AE-related early discontinuations compared to those 70-74 years. Further research is needed to evaluate tolerability and improve the delivery of palbociclib in older adults. CLINICALTRIALS: gov:NCT03633331.

Physician-level variation in axillary surgery in older adults with T1N0 hormone receptor-positive breast cancer: A retrospective population-based cohort study.

INTRODUCTION: We sought to determine how considerations specific to older adults impact between- and within-surgeon variation in axillary surgery use in women ≥70 years with T1N0 HR+ breast cancer. MATERIALS AND METHODS: Females ≥70 years with T1N0 HR+/HER2-negative breast cancer diagnosed from 2013 to 2015 in SEER-Medicare were identified and linked to the American Medical Association Masterfile. The outcome of interest was axillary surgery. Key patient-level variables included the Charlson Comorbidity Index (CCI) score, frailty (based on a claims-based frailty index score), and age (≥75 vs <75). Multilevel mixed models with surgeon clusters were used to estimate the intracluster correlation coefficient (ICC) (between-surgeon variance), with 1-ICC representing within-surgeon variance. RESULTS: Of the 4410 participants included, 6.1% had a CCI score of ≥3, 20.7% were frail, and 58.3% were ≥ 75 years; 86.1% underwent axillary surgery. No surgeon omitted axillary surgery in all patients, but 42.3% of surgeons performed axillary surgery in all patients. In the null model, 10.5% of the variance in the axillary evaluation was attributable to between-surgeon differences. After adjusting for CCI score, frailty, and age in mixed models, between-surgeon variance increased to 13.0%. DISCUSSION: In this population, axillary surgery varies more within surgeons than between surgeons, suggesting that surgeons are not taking an "all-or-nothing" approach. Comorbidities, frailty, and age accounted for a small proportion of the variation, suggesting nuanced decision-making may include additional, unmeasured factors such as differences in surgeon-patient communication.

Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer-Cyclin-Dependent Kinase 4 and 6 Inhibitors: ASCO Guideline Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

PURPOSE: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. METHODS: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). RESULTS: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001). CONCLUSION: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes. CLINICAL TRIAL: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.

Prognosis and treatment outcomes for patients with stage IA triple-negative breast cancer.

To evaluate the role of chemotherapy in stage IA triple-negative breast cancer, we conducted a retrospective population-based study including 8601 patients. The use of chemotherapy significantly increased from 2010 to 2019 in patients with T1b and T1c tumors (p = 0.001 and p < 0.001, respectively). Receipt of chemotherapy was associated with improved breast cancer-specific survival (BCSS, adjusted hazard ratio = 0.70; p = 0.006), particularly in patients with T1c tumors (5-year BCSS 94.5% vs. 91.2%).

Racial disparities in outcomes of patients with stage I-III triple-negative breast cancer after adjuvant chemotherapy: a post-hoc analysis of the E5103 randomized trial.

PURPOSE: Breast cancer mortality is higher in Black women than other racial groups. This difference has been partially attributed to a higher proportion of triple-negative breast cancer (TNBC). However, it is uncertain if survival disparities exist in racially diverse TNBC patients receiving similar treatments. Here, we examine racial differences in disease-related outcomes in TNBC patients treated on the E5103 clinical trial. METHODS: From 2007 to 2011, 4,994 patients with stage I-III HER2-negative breast cancer were randomized to adjuvant chemotherapy with or without bevacizumab. This analysis was limited to the subset of 1,742 TNBC patients with known self-reported race. Unadjusted Kaplan-Meier curves and adjusted Cox-Proportional Hazards models were used to determine breast cancer events and survival outcomes. RESULTS: Of the analysis population, 51 (2.9%) were Asian, 269 (15.4%) Black, and 1422 (81.6%) White. Median age was 51 years. Patient characteristics, treatment arm, and local therapies were similar across racial groups. White women were more commonly node-negative (56% vs. 49% and 44% in Asian and Black women, respectively; p < 0.01). At a median follow-up of 46 months, unadjusted Kaplan-Meier locoregional and distant recurrence, and disease-free and overall survival, did not differ significantly by race. In Cox models adjusted for patient and tumor characteristics and treatment arm, race was not associated with any disease event. Larger tumor size and nodal involvement were consistently associated with breast cancer events. CONCLUSION: This clinical trial population of similarly treated TNBC patients showed no racial differences in breast cancer outcomes. Disease extent, rather than race, was associated with disease events.

Mortality Risks Over 20 Years in Men With Stage I to III Hormone Receptor-Positive Breast Cancer.

Importance: In women with hormone receptor-positive (HR+) breast cancer, the risk of distant recurrence and death persists for at least 20 years from diagnosis. The risk of late mortality in men with HR+ breast cancer has not been reported. Objective: To report 20-year risks of breast cancer-specific mortality (BCSM) and non-BCSM in men with stage I to III HR+ breast cancer and identify factors associated with late BCSM. Design, Setting, and Participants: An observational cohort study was conducted of men diagnosed with HR+ breast cancer from 1990 to 2008, using population-based data from the Surveillance, Epidemiology, and End Results program. Men diagnosed with stage I to III HR+ breast cancer were included in the analysis. Cumulative incidence function was used to estimate the outcomes of baseline clinicopathologic variables regarding cumulative risk of BCSM and non-BCSM since diagnosis. Smoothed hazard estimates over time were plotted for BCSM. Fine and Gray multivariable regression evaluated the association of preselected variables with BCSM, conditional on having survived 5 years. Main Outcome Measure: BCSM. Results: A total of 2836 men with stage I to III HR+ breast cancer were included, with a median follow-up of 15.41 (IQR, 12.08-18.67) years. Median age at diagnosis was 67 (IQR, 57-76) years. The cumulative 20-year risk of BCSM was 12.4% for stage I, 26.2% for stage II, and 46.0% for stage III. Smoothed annual hazard estimates for BCSM revealed an increase in late hazard rates with each incremental node category, reaching a bimodal distribution in N3 and stage III, with each having peaks in hazard rates at 4 and 11 years. Among patients who survived 5 years from diagnosis, the adjusted BCSM risk was higher for those younger than 50 years vs older than 64 years, those with grade II or III/IV vs grade I tumors, and stage II or III vs stage I disease. Conclusions and Relevance: The findings of this study suggest that, in men with stage I to III HR+ breast cancer, the risk of BCSM persists for at least 20 years and depends on traditional clinicopathologic factors, such as age, tumor stage, and tumor grade. Among men with higher stages of disease, the kinetics of the BCSM risk appear different from the risk that has been reported in women.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Trends in Locoregional Therapy in Older Women with Early-Stage Hormone Receptor-Positive Breast Cancer by Frailty and Life Expectancy.

BACKGROUND: In women ≥ 70 years of age with T1N0 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, breast surgery type and omission of axillary surgery or radiation therapy (RT) do not impact overall survival. Although frailty and life expectancy ideally factor into therapy decisions, their impact on therapy receipt is unclear. We sought to identify trends in and factors associated with locoregional therapy type by frailty and life expectancy. METHODS: Women ≥ 70 years of age with T1N0 HR+/HER2- breast cancer diagnosed in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 2010 and 2015 were stratified by validated claims-based frailty and life expectancy measures. Therapy trends over time by regimen intensity ('high intensity': lumpectomy + axillary surgery + RT, or mastectomy + axillary surgery; 'moderate intensity': lumpectomy + RT, lumpectomy + axillary surgery, or mastectomy only; or 'low intensity': lumpectomy only) were analyzed. Factors associated with therapy type were identified using generalized linear mixed models. RESULTS: Of 16,188 women, 21.8% were frail, 22.2% had a life expectancy < 5 years, and only 12.3% fulfilled both criteria. In frail women with a life expectancy < 5 years, high-intensity regimens decreased significantly (48.8-31.2%; p < 0.001) over the study period, although in 2015, 30% still received a high-intensity regimen. In adjusted analyses, frailty and life expectancy < 5 years were not associated with breast surgery type but were associated with a lower likelihood of axillary surgery (frailty: odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76-0.96; life expectancy < 5 years: OR 0.22, 95% CI 0.20-0.25). Life expectancy < 5 years was also associated with a lower likelihood of RT receipt in breast-conserving surgery patients (OR 0.30, 95% CI 0.27-0.34). CONCLUSIONS: Rates of high-intensity therapy are decreasing but overtreatment persists in this population. Continued efforts aimed at appropriate de-escalation of locoregional therapy are needed.

Racial Disparities in Locoregional Recurrence in Postmenopausal Patients with Stage I-III, Hormone Receptor-Positive Breast Cancer Enrolled in the NSABP B-42 Clinical Trial.

BACKGROUND: There are limited data examining racial disparities in locoregional recurrence (LRR) among women with access to high-quality care. We aimed to examine differences in late LRR by race in patients with stage I-IIIA, hormone receptor-positive (HR+) breast cancer enrolled in the National Surgical Adjuvant Breast and Bowel (NSABP) B-42 trial. METHODS: From 2006 to 2010, 3966 postmenopausal women with stage I-IIIA HR+ breast cancer who were disease-free after 5 years of endocrine therapy were randomized to an additional 5 years of endocrine therapy or placebo. Patients were excluded if multi-racial or if race was unknown. Kaplan-Meier curves were used to estimate 6-year LRR from the time of trial registration and according to race. Cox proportional hazards models were used for adjusted survival analyses. RESULTS: Overall, 3929 NSABP B-42 patients were included: 3688 (93.9%) White, 151 (3.8%) Black, and 90 (2.3%) Asian patients. Median follow-up was 75.2 months. Overall estimated 6-year LRR from trial registration was 1.8% and differed by race: LRR rates were 1.7% in White women, 4.9% in Black women, and 0% in Asian women (p = 0.046). Adjusted Cox proportional hazards analysis found Black race to be independently associated with LRR (hazard ratio [HzR] 2.36, 95% confidence interval [CI] 1.01-5.49; p = 0.047). Node-positivity was also associated with increased LRR (HzR 1.75, 95% CI 1.07-2.86; p = 0.025). Adjusted Cox analysis found LRR (HzR 2.32, 95% CI 1.33-4.06; p = 0.003) to be associated with increased overall mortality; however, race was not independently associated with mortality. CONCLUSION: Among postmenopausal patients with stage I-IIIA HR+ breast cancer in the NSABP B-42 trial, racial differences in late LRR were present, with the highest LRR in Black women.

Racial and Ethnic Disparities in Outcomes After Breast-Conserving Therapy and Endocrine Therapy for DCIS: A Post-Hoc Analysis of the NSABP B-35 Randomized Clinical Trial.

BACKGROUND: Racial and ethnic disparities in outcomes after treatment for ductal carcinoma in situ (DCIS) are largely unknown. The objective of this study was to examine breast cancer outcomes by race and ethnicity in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 clinical trial. PATIENTS AND METHODS: The NSABP B-35 trial randomized postmenopausal women with hormone receptor-positive DCIS treated with breast-conserving therapy to 5 years of tamoxifen or anastrozole. In total, 3104 women were enrolled between 2003 and 2006. For this analysis, patients without complete self-reported race and ethnicity or with immediate trial dropout were excluded. Kaplan-Meier curves and adjusted Cox-proportional hazards models were used for analyses. RESULTS: Of the 3061 women included, 2614 (85.4%) were non-Hispanic white (NHW), 255 (8.3%) were non-Hispanic Black (NHB), 95 (3.1%) were Hispanic, and 96 (3.1%) were Asian or Pacific Islander (API). Endocrine therapy assignment and duration were well balanced between racial and ethnic groups. Median follow-up was 9 years; unadjusted Kaplan-Meier curves did not show any racial differences in disease events. Adjusted Cox-proportional hazards models found API (versus NHW) race to be associated with higher local recurrence [hazard ratio (HzR) 2.45, p = 0.035] and NHB race to be associated with higher distant recurrence (HzR 5.03, p = 0.020) and breast cancer mortality (HzR 3.83, p = 0.046). CONCLUSIONS: Despite similar locoregional treatments and standard endocrine therapy in a clinical trial population, racial and ethnic disparities exist in long-term outcomes for hormone-receptor-positive DCIS. These findings suggest that factors outside of access and treatment may impact DCIS outcomes by race and ethnicity.

Inequities in referrals to a breast cancer risk assessment and prevention clinic: a mixed methods study.

BACKGROUND: Inequitable access to personalized breast cancer screening and prevention may compound racial and ethnic disparities in outcomes. The Breast Cancer Personalized Risk Assessment, Education and Prevention (B-PREP) program, located within the Brigham and Women's Hospital (BWH) Comprehensive Breast Health Center (BHC), provides care to patients at high risk for developing breast cancer. We sought to characterize the differences between BWH primary care patients referred specifically to B-PREP for risk evaluation and those referred to the BHC for benign breast conditions. Through interviews with primary care clinicians, we sought to explore contributors to potentially inequitable B-PREP referral patterns. METHODS: We used electronic health record data and the B-PREP clinical database to identify patients referred by primary care clinicians to the BHC or B-PREP between 2017 and 2020. We examined associations with likelihood of referral to B-PREP for risk assessment. Semi-structured interviews were conducted with nine primary care clinicians from six clinics to explore referral patterns. RESULTS: Of 1789 patients, 78.0% were referred for benign breast conditions, and 21.5% for risk assessment. In multivariable analyses, Black individuals were less likely to be referred for risk than for benign conditions (OR 0.38, 95% CI:0.23-0.63) as were those with Medicaid/Medicare (OR 0.72, 95% CI:0.53-0.98; OR 0.52, 95% CI:0.27-0.99) and those whose preferred language was not English (OR 0.26, 95% CI:0.12-0.57). Interviewed clinicians described inconsistent approaches to risk assessment and variable B-PREP awareness. CONCLUSIONS: In this single-site evaluation, among individuals referred by primary care clinicians for specialized breast care, Black, publicly-insured patients, and those whose preferred language was not English were less likely to be referred for risk assessment. Larger studies are needed to confirm these findings. Interventions to standardize breast cancer risk assessment in primary care may improve equity.

Estimating mortality in women with triple-negative breast cancer: The 'ESTIMATE triple-negative' tool.

PURPOSE: Triple-negative breast cancer (TNBC) is associated with a high risk of breast cancer-specific mortality (BCSM). Estimating the risk of BCSM and non-BCSM in TNBC would aid clinical decision-making. We developed the tool 'ESTIMATE-TN', to assess BCSM, non-BCSM, and all-cause mortality in non-metastatic TNBC. METHODS: Using Surveillance, Epidemiology, and End Results (SEER), we created an interactive tool that provides a nonparametric estimate of the cumulative risk of BCSM and non-BCSM between years 0 and 7 from diagnosis, accounting for baseline clinical and pathologic variables, using Gray's subdistribution method. RESULTS: We included 37,293 women with TNBC diagnosed during 2010-2017. Most patients were White (71.9%) and aged 50-69 years (51.3%). Most tumour characteristics were high-grade (78.6%), T2 (42.4%), and N0 (69.5%). ESTIMATE-TN allows to input patient and tumour characteristics, and the preferred timeframe. For example, patients aged 50-59 years with a new diagnosis of T2, N1, high-grade TNBC have a risk of BCSM at 7 years of 30.8% (95% confidence interval [CI]: 26.3-35.4%) and a risk of non-BCSM over the same period of 2.8% (95% CI: 1.3-4.3%). After 3 years from initial diagnosis, the residual cumulative risks of BCSM and non-BCSM at 7 years are 17.4% (95% CI: 12.6-22.2%) and 1.1% (95% CI: 0-2.5%), respectively. CONCLUSIONS: ESTIMATE-TN is an interactive tool for TNBC that can be used to integrate population-based risks of BCSM and non-BCSM based on patient and tumour characteristics, facilitating our understanding of competing risks of death, which can aid clinical decision-making.

Breast cancer treatment receipt and the role of financial stress, health literacy, and numeracy among diverse breast cancer survivors.

PURPOSE: Disparities in breast cancer treatment for low-income and minority women are well documented. We examined economic hardship, health literacy, and numeracy and whether these factors were associated with differences in receipt of recommended treatment among breast cancer survivors. METHODS: During 2018-2020, we surveyed adult women diagnosed with stage I-III breast cancer between 2013 and 2017 and received care at three centers in Boston and New York. We inquired about treatment receipt and treatment decision-making. We used Chi-squared and Fisher's exact tests to examine associations between financial strain, health literacy, numeracy (using validated measures), and treatment receipt by race and ethnicity. RESULTS: The 296 participants studied were 60.1% Non-Hispanic (NH) White, 25.0% NH Black, and 14.9% Hispanic; NH Black and Hispanic women had lower health literacy and numeracy and reported more financial concerns. Overall, 21 (7.1%) women declined at least one component of recommended therapy, without differences by race and ethnicity. Those not initiating recommended treatment(s) reported more worry about paying large medical bills (52.4% vs. 27.1%), worse household finances since diagnosis (42.9% vs. 22.2%), and more uninsurance before diagnosis (9.5% vs. 1.5%); all P < .05. No differences in treatment receipt by health literacy or numeracy were observed. CONCLUSION: In this diverse population of breast cancer survivors, rates of treatment initiation were high. Worry about paying medical bills and financial strain were frequent, especially among non-White participants. Although we observed associations of financial strain with treatment initiation, because few women declined treatments, understanding the scope of impact is limited. Our results highlight the importance of assessments of resource needs and allocation of support for breast cancer survivors. Novelty of this work includes the granular measures of financial strain and inclusion of health literacy and numeracy.

Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor-Positive Breast Cancer: Implications for Guidance and Reimbursement.

PURPOSE: To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS: RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS: Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION: Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.

Clonal hematopoiesis in older patients with breast cancer receiving chemotherapy.

BACKGROUND: The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints. METHODS: We examined serial samples from 40 older women with triple-negative or hormone receptor-positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks). RESULTS: CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02). CONCLUSIONS: Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.

Racial and Ethnic Disparities in Locoregional Recurrence Among Patients With Hormone Receptor-Positive, Node-Negative Breast Cancer: A Post Hoc Analysis of the TAILORx Randomized Clinical Trial.

Importance: Whether racial and ethnic disparities in locoregional recurrence (LRR) exist among patients with similar access to care treated in randomized clinical trials is unknown. Objective: To 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 Participants: This 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 <11), endocrine therapy alone vs chemotherapy followed by endocrine therapy (recurrence score 11-25), or chemotherapy followed by endocrine therapy (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 Measures: Locoregional 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. Results: Of 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 < .001). In survival analyses adjusted for patient, tumor, and treatment factors, Asian race (hazard ratio, 1.91 [95% CI, 1.12-3.29]) and Black race (1.78 [1.15-2.77]) were independently associated with LRR. In adjusted survival analyses for breast cancer mortality, LRR was independently associated with increased breast cancer mortality (hazard ratio, 5.71 [95% CI, 3.50-9.31]). Conclusions and Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT00310180.