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Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.

ABSTRACT: The association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy.The effect of black race on disease-free and overall survival was evaluated using Cox proportional hazards models adjusted for multiple covariates in a clinical trial population that was treated with anthracycline- and taxane-containing chemotherapy. Categorical variables were compared using the Fisher exact test. All P values are two-sided.Of 4817 eligible patients, 405 (8.4%) were black. Compared with nonblack patients, black patients had a higher rate of triple-negative disease (31.9% vs 17.2%; P < .001) and a higher body mass index (median: 31.7 vs 27.4 kg/m(2); P < .001). Black race was statistically significantly associated with worse disease-free survival (5-year disease-free survival, black vs nonblack: 76.7% vs 84.5%; hazard ratio of recurrence or death = 1.58, 95% confidence interval = 1.19 to 2.10, P = .0015) and overall survival (5-year overall survival, black vs nonblack: 87.6% vs 91.9%; hazard ratio of death = 1.49, 95% confidence interval = 1.05 to 2.12, P = .025) in patients with hormone receptor-positive HER2-negative disease but not in patients with triple-negative or HER2-positive disease. In a model that included black race, hormone receptor-positive HER2-negative disease vs other subtypes, and their interaction, the interaction term was statistically significant for disease-free survival (P = .027) but not for overall survival (P = .086).Factors other than disparities in care or aggressive disease contribute to increased recurrence in black women with hormone receptor-positive breast cancer.

SUBMITTER: Sparano JA

PROVIDER: S-EPMC3295746 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.

Sparano Joseph A JA Wang Molin M Zhao Fengmin F Stearns Vered V Martino Silvana S Ligibel Jennifer A JA Perez Edith A EA Saphner Tom T Wolff Antonio C AC Sledge George W GW Wood William C WC Davidson Nancy E NE

Journal of the National Cancer Institute 20120116 5

<h4>Background</h4>The association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy.<h4>Methods</h4>The effect of black race on disease-free and overall surviva ...[more]

PMID: 22250182

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Project description:ImportanceRace disparities persist in breast cancer mortality rates. One factor associated with these disparities may be differences in symptom burden, which may reduce chemotherapy tolerance and increase early treatment discontinuation.ObjectivesTo compare symptom burden by race among women with early-stage breast cancer before starting chemotherapy and quantify symptom differences explained by baseline characteristics.Design, setting, and participantsA cross-sectional analysis of symptom burden differences by race among Black and White women with a diagnosis of stage I to III, hormone receptor-positive breast cancer who had a symptom report collected before chemotherapy initiation in a large cancer center in the southern region of the US from January 1, 2007, through December 31, 2015. Analyses were conducted from November 1, 2019, to March 31, 2021. Blinder-Oaxaca decomposition was used, adjusting for baseline sociodemographic and clinical characteristics.Main outcomes and measuresFour symptom composite scores with a mean (SD) of 50 (10) were reported before starting chemotherapy (baseline) and were derived from symptom items: general physical symptoms (11 items), treatment adverse effects (8 items), acute distress (4 items), and despair (7 items). Patients rated the severity of each symptom they experienced in the past week on a scale of 0 to 10 (where 0 indicates not a problem and 10 indicates as bad as possible).ResultsA total of 1338 women (mean [SD] age, 54.6 [11.6] years; 420 Black women [31.4%] and 918 White women [68.6%]) were included in the study. Before starting chemotherapy, Black women reported a statistically significantly higher (ie, worse) symptom composite score than White women for adverse effects (44.5 vs 43.8) but a lower acute distress score (48.5 vs 51.0). Decomposition analyses showed that Black patients' characteristics were associated with higher symptom burden across all 4 scores. However, these differences were offset by relatively greater, statistically significant, unexplained physical, distress, and despair symptom reporting by White patients.Conclusions and relevanceIn this study, before starting chemotherapy, Black patients with early-stage breast cancer reported significantly higher burden for symptoms that may be exacerbated with chemotherapy and lower distress symptoms compared with White patients. Future studies should explore how symptoms change before and after treatment and differ by racial/ethnic groups and how they are associated with treatment adherence and mortality disparities.

Project description:PurposeHormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer is associated with low levels of stromal tumor-infiltrating lymphocytes (sTIL) and PD-L1, and demonstrates poor responses to checkpoint inhibitor therapy. Evaluating the effect of standard chemotherapy on the immune microenvironment may suggest new opportunities for immunotherapy-based approaches to treating HR+/HER2- breast tumors.Experimental designHR+/HER2- breast tumors were analyzed before and after neoadjuvant chemotherapy. sTIL were assessed histologically; CD8+ cells, CD68+ cells, and PD-L1 staining were assessed immunohistochemically; whole transcriptome sequencing and panel RNA expression analysis (NanoString) were performed.ResultsNinety-six patients were analyzed from two cohorts (n = 55, Dana-Farber cohort; n = 41, MD Anderson cohort). sTIL, CD8, and PD-L1 on tumor cells were higher in tumors with basal PAM50 intrinsic subtype. Higher levels of tissue-based lymphocyte (sTIL, CD8, PD-L1) and macrophage (CD68) markers, as well as gene expression markers of lymphocyte or macrophage phenotypes (NanoString or CIBERSORT), correlated with favorable response to neoadjuvant chemotherapy, but not with improved distant metastasis-free survival in these cohorts or a large gene expression dataset (N = 302). In paired pre-/postchemotherapy samples, sTIL and CD8+ cells were significantly decreased after treatment, whereas expression analyses (NanoString) demonstrated significant increase of multiple myeloid signatures. Single gene expression implicated increased expression of immunosuppressive (M2-like) macrophage-specific genes after chemotherapy.ConclusionsThe immune microenvironment of HR+/HER2- tumors differs according to tumor biology. This cohort of paired pre-/postchemotherapy samples suggests a critical role for immunosuppressive macrophage expansion in residual disease. The role of macrophages in chemoresistance should be explored, and further evaluation of macrophage-targeting therapy is warranted.

Project description:BackgroundNeoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer.MethodsBased on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0).ResultsOf 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET.ConclusionsAlthough the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.

Project description:BackgroundAKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited.MethodsIn a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed.ResultsOverall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.ConclusionsCapivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.).

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Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.

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Race and hormone receptor-positive breast cancer outcomes in a randomized chemotherapy trial.

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