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Background: Patient-reported outcomes (PRO) assess symptom burden and health-related quality of life (HRQL) more accurately than clinical report. We previously found that treatment-emergent adverse events (CTCAE V3.0) did not impact efficacy in the main NCIC MA.27 trial, although many women discontinued treatment early. The purpose of this substudy was to obtain PROs in MA.27/E1Z03 participants to evaluate treatment-related side effects and HRQL between exemestane and anastrozole and to identify predictors of treatment discontinuation. Methods: The Eastern Cooperative Oncology Group trial (E1Z03) assessed PROs in a sample of MA.27 patients (N=686; 99.3% participation rate). Participants completed the 56-item Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) pre-treatment and at months 3, 6, 12 and 24 to assess breast-cancer specific concerns, side effects of hormonal treatments and HRQL. We used 1) Wilcoxon rank sum test to compare treatment-related symptoms and HRQL between trial arms; 2) linear mixed effect models to test differences in changes of treatment-related symptoms and HRQL between trial arms; 3) linear regression to examine the effects of symptoms on HRQL and 4) adjusted Cox regression to assess predictors of treatment duration. Results: Participants included 371 women randomized to anastrozole and 315 randomized to exemestane. Demographic and disease characteristics were balanced between trial arms. Participants were a mean age of 65.6 yrs (SD=9.2), White (95.9%), ECOG PS of 0 (87.2%), stage T1 (75.5%) or T2 (22.7%), and stage N0 (73.9%) or N1 (16.3%). Prior treatments included partial mastectomy (65.7%), chemotherapy (27.8%) and radiotherapy (51.7%). Treatment-related symptoms measured by 23 items from the FACT-ES did not differ between treatment arms at months 3, 6, 12 and 24 and the timeline change of treatment-related symptoms was similar between treatment arms (p = ns). HRQL was significantly impacted by decreased libido, weight gain, feeling bloated, breast sensitivity, mood swings, irritability, join pain, nausea and bother by treatment side effects (p < 0.001). 248 participants were off-treatment by 4.1 yrs. A Cox model adjusted for other symptoms, demographic and disease characteristics indicated the hazard of discontinuing treatment early increased by 29% when the severity of being bothered by side effects at baseline increased by 1 point (HR=1.29, 95% CI:1.09−1.54). At baseline, patients with prior treatments or taking more medicines reported more bother by side effects (p < 0.001). Increased joint pain in the first 3 months after treatment was also associated with increased hazard of discontinuing treatment early (HR=1.13, 95% CI: 1.01−1.28). Conclusions: PRO assessment indicated comparable symptom burden and HRQL among postmenopausal women randomized to anastrozole or exemestane, with increasing symptom burden over time negatively affecting HRQL. Patients who 1) initiate an aromatase inhibitor (AI) with bother by side effects from prior treatment and concomitant medications and 2) experience increased joint pain during the first 3 months of AI therapy are at risk for early discontinuation of AI therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S6-2.

Background: Black race is associated with worse outcomes in localized hormone receptor (HR)-positive breast cancer in population-based and in clinical trial cohorts, whether using self-identified race (Albain et al. JNCI 2009 [PMID: 19584328; Sparano et al. JNCI 2012 [PMID: 22250182) or genetically-identified race (Schneider et al. J Precision Oncol 2017 [PMID: 29333527]). This disparity persists after adjustment for treatment delivery parameters (Hershman et al. JCO 2009 [PMID:19307504]). We evaluated clinicopathologic characteristics, treatment delivered and clinical outcomes in the Trial Assigning Individualized Options for Treatment (TAILORx) by race and ethnicity (Sparano et al. NEJM 2018 [PMID: 29860917]). Methods: The analysis included 9719 evaluable TAILORx participants. The association between clinical outcomes and race (white, black, Asian, other/unknown) and ethnicity (Hispanic vs. non-Hispanic) was examined, including invasive disease-free survival (iDFS), distant relapse-free interval (DRFI), relapse-free interval (RFI), and overall survival (OS). Proportional hazards models were fit including age (5 categories), tumor size (>2 cm vs. <=2 cm), histologic grade (high vs. medium vs. low vs. unknown), continuous recurrence score (RS), race, and ethnicity in the overall population and randomized treatment arms in the RS 11-25 cohort. Results: The study population included 8189 (84%) whites, 693 (7%) blacks, 405 (4%) Asians, and 432 (4%) with other/unknown race. Regarding ethnicity, 7635 (79%) were non-Hispanic, 889 (9%) Hispanic, and 1195 (12%) unknown. There was no significant difference in RS distribution (p=0.22) in blacks compared with whites, or in median (17 vs. 17) or mean RS (19.1 vs. 18.2). There was likewise no difference in Hispanic vs. non-Hispanic ethnicity for RS distribution (p=0.72) or median (17 vs. 17) or mean RS (18.5 vs. 18.0). Black race (39% vs. 30%) and Hispanic ethnicity (39% vs. 30%) were both associated with younger age (</=50 years) at diagnosis. The use and type of adjuvant chemotherapy and endocrine therapy, and duration of endocrine therapy, were similar in black (vs. white) and Hispanic (vs. non-Hispanic) populations. In proportional hazards models, black race (compared with white race) was associated with worse clinical outcomes in the entire population and in those with a RS 11-25 (see table). Hispanic ethnicity was generally associated with better outcomes (compared with non-Hispanic ethnicity). For the cohort with a RS of 11-25, there was no evidence for chemotherapy benefit for any racial or ethnic group. Race (black vs.white) and clinical outcomes in proportional hazards modelsClinical endpointEntire Population (N=693 black) Hazard ratio for eventRS 11-25 (N=471 black) Hazard ratio for eveniDFS1.33 (p=0.005)1.49 (p=0.001)DRFI1.21 (p=0.28)1.60 (p=0.02)RFI1.39 (p=0.02)1.80 (p<0.001)OS1.52 (p=0.005)1.67 (p=0.003 Conclusions: In patients eligible and selected for participation in TAILORx, black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy. This adds to an emerging body of evidence suggesting a biologic basis or other factors contributing to racial disparities in HR-positive breast cancer that requires further evaluation. Citation Format: Albain K, Gray RJ, Sparano JA, Makower DF, Pritchard KI, Hayes DF, Geyer, Jr. CE, Dees EC, Goetz MP, Olson, Jr. JA, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Ravdin PM, Keane MM, Gomez HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge, Jr. GW. Race, ethnicity and clinical outcomes in hormone receptor-positive, HER2-negative, node-negative breast cancer: results from the TAILORx trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-07.