Real-world evidence on predictors of survival for hormone-positive and triple-negative advanced breast cancer by treatment and BRCA status in the United States

ASCO 2022 Presentation
Authors Dongmu Zhang, Leon Raskin, Wendy Sebby, Lei He, Sandeep Pawar, Steven A Narod, Olufunmilayo I. Olopade, Alexander Liede

Background: Factors that affect overall survival (OS) for women with metastatic or recurrent breast cancer (BC) and BRCA1 or BRCA2 mutations (BRCA+) are a matter of debate. We analyzed electronic health records (EHR) from centers across the US to examine the effect of bilateral salpingo oophorectomy (BSO) and other factors on OS across treatment and molecular subtypes with emphasis on hormone-positive (HR+) and triple-negative BC (TNBC).

Methods: A cohort of women diagnosed with stage 3 or 4 HR+ or TNBC from 1-Jan-2015 to 31-Dec-2019 was identified from EHR (Tempus Labs, Chicago, IL). BRCA+ was confirmed from medical notes and laboratory reports. A comparator group included HR+ and TNBC with no record of BRCA testing (Non-BRCA). Kaplan-Meier and Cox proportional hazards were used to evaluate predictors of OS from earliest diagnosis in multivariate models by BRCA status and molecular phenotype; treatment exposure (any time), mastectomy and BSO were treated as time-dependent variables.

Results: We identified 1227 women with median age of 53 years (range 18-89) at BC diagnosis and median follow up of 26.1 months (max > 26 years) and 358 deaths. Two-thirds had distant visceral or bone metastases, almost 60% were recurrent after original stage 1-3 BC; 302 women were stage 3 and 296 stage 4 at BC. The BRCA+ cohort included 439 women (195 BRCA1, 220 BRCA2, 24 “BRCA” mutation; 265 HR+, 142 TNBC) and median age at BC was 46 years (44 BRCA1, 47 BRCA2). Non-BRCA cohort consisted of 788 women with a median age of 57 at BC (378 HR+, 341 TNBC). BRCA+ had longer OS than non-BRCA (P= 0.0001); HR+ had longer OS than TNBC (P= 0.0001). For 331 TNBC, chemotherapeutic regimens were most common first line treatment; few (17%) received third line and 31% had no evidence of receiving systemic therapy. Age ≤50, BRCA+, and mastectomy were associated with increased OS in HR+; BRCA+ status and mastectomy were predictors of increased OS whereas platinum-based chemotherapy was associated with decreased OS in TNBC (Table). Across molecular subtypes, BSO was not an independent predictor of OS and most women (92%) had BSO after BC diagnosis.

Conclusions: Regardless of BRCA status, women with advanced TNBC were almost exclusively treated with chemotherapy, which highlights the remaining unmet need for effective treatment options. Taking timing of BSO and other interventions into account is critical to understanding their effects of BC mortality.

Multivariate analyses (*time-varying).

HR+ (N = 643) TNBC (N = 483)
HR (95% CI) P HR (95% CI) P
age > 50 1.64 (1.19, 2.3) 0.0026 1.03 (0.74, 1.4) 0.85
BRCA1 vs. Non-BRCA 0.16 (0.07, 0.4) < .0001 0.32 (0.18, 0.59) 0.0002
BRCA2 vs. Non-BRCA 0.2 (0.1, 0.37) < .0001 0.28 (0.1, 0.76) 0.013
BSO* 0.88 (0.6, 1.3) 0.52 1.2 (0.75, 1.94) 0.45
CDK* 1.3 (0.9, 1.9) 0.16 n/a
Platinum-based chemo* n/a 2.0 (1.45, 2.77) < .0001
Mastectomy* 0.6 (0.44, 0.82) 0.0015 0.48 (0.34, 0.7) < .0001