Background:BRCA-mutated breast cancer remains a heterogeneous disease, with variations in histology, response to treatment, and survival outcomes. These cancers are more likely to be negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) or triple negative (TN). However, some are hormone receptor-positive (HR+) and amenable to hormone treatment. We compared treatment patterns and clinical outcomes in patients with BRCA-mutated metastatic breast cancer (MBC) who were either TN or HR+/HER2-negative using real-world data.

Methods: This retrospective study examined progression-free survival (PFS) and overall survival (OS) in a US community oncology sample of adult patients with BRCA-mutated MBC for up to three lines of treatment. Medical records from the Vector Oncology Data Warehouse were used. Disease progression was determined from chart review. Overall survival was measured from start of first-line (L1) treatment; patients without evidence of death were censored at the last observed visit. Cox models of PFS and OS were adjusted for age, race, performance status, tumor grade, and bone metastasis.

Results: The study included 57 TN patients and 57 HR+ patients with BRCA mutation. BRCA 1 and BRCA 2 mutations were more frequent in patients with TN disease and HR+ disease, respectively. In TN disease, the most common L1 treatments, n (%), were bevacizumab 10 (20.4%), capecitabine 10 (20.4%), carboplatin/gemcitabine 8 (16.3%), carboplatin plus other 7 (14.3%), and paclitaxel 5 (10.2%). In HR+ patients, L1 treatments included aromatase inhibitors 14 (24.6%), fulvestrant 10 (17.5%), tamoxifen 7 (12.3%), and capecitabine 5 (8.8%). The between-group difference in PFS following L1 was statistically significant favoring HR+ disease (see Table), but not following lines 2 or 3. Overall survival was also significantly longer for the HR+ group (see Table). Presence of bone metastasis was a significant predictor of higher risk for disease progression.

Conclusions: In this real-world sample of patients with BRCA1- or BRCA2-mutated MBC, those with TN disease had significantly worse outcomes after L1 (PFS, OS) compared with similar patients with HR+ disease. Triple-negative disease was associated with poorer prognosis, demonstrating a need for new treatment options for patients with BRCA-mutated TN MBC.

Baseline Characteristics and Outcomes

  TN N=57 HR+ N=57 
Age, median yrs 46 51 
Performance Status Impaired, n (%) 2 (3.5) 4 (7.0) 
Any CCIa Comorbidity, n (%) 18 (31.6) 11 (19.3) 
  
BRCA1, n (%)     
40 (70.2) 18 (31.6)b 
– 17 (29.8) 39 (68.4)b 
BRCA2, n (%)     
16 (28.1) 39 (68.4)b 
– 41 (71.9) 18 (31.6)b 
  
PFS L1 
Median Months (95% CI) 6.13 (4.2, 9.4) 12.09 (7.1, 14.5) 
Adj PFS HR (95% CI) for TN vs HR+ 1.714 (1.082, 2.717) P=.022 
Bone Metastasis HR (95% CI) Present vs Absent 1.631 (1.039, 2.561) P=.033 
OS from Start of L1 
Median Months (95% CI) 23.43 (15.4, 26.4) 38.41 (28.9, 67.4) 
Adj OS HR (95% CI) for TN vs HR+ 1.869 (1.072, 3.256) P=.027 
HR (95% CI) for Race Minority/Unknown vs White 2.040 (1.118, 3.723) P=.020 
HR (95% CI) for Tumor G3 vs Other 3.010 (1.299, 6.973) P=.010 
aCharlson Comorbidity Index 
bP<.001 
  TN N=57 HR+ N=57 
Age, median yrs 46 51 
Performance Status Impaired, n (%) 2 (3.5) 4 (7.0) 
Any CCIa Comorbidity, n (%) 18 (31.6) 11 (19.3) 
  
BRCA1, n (%)     
40 (70.2) 18 (31.6)b 
– 17 (29.8) 39 (68.4)b 
BRCA2, n (%)     
16 (28.1) 39 (68.4)b 
– 41 (71.9) 18 (31.6)b 
  
PFS L1 
Median Months (95% CI) 6.13 (4.2, 9.4) 12.09 (7.1, 14.5) 
Adj PFS HR (95% CI) for TN vs HR+ 1.714 (1.082, 2.717) P=.022 
Bone Metastasis HR (95% CI) Present vs Absent 1.631 (1.039, 2.561) P=.033 
OS from Start of L1 
Median Months (95% CI) 23.43 (15.4, 26.4) 38.41 (28.9, 67.4) 
Adj OS HR (95% CI) for TN vs HR+ 1.869 (1.072, 3.256) P=.027 
HR (95% CI) for Race Minority/Unknown vs White 2.040 (1.118, 3.723) P=.020 
HR (95% CI) for Tumor G3 vs Other 3.010 (1.299, 6.973) P=.010 
aCharlson Comorbidity Index 
bP<.001 

Citation Format: Houts AC, Olufade TO, Shenolikar R, Walker MS. Real-world clinical outcomes in BRCA-positive metastatic breast cancer patients treated in the community oncology setting [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-15.