Abstract P5-16-02: Pathological complete response is associated with excellent outcomes in BRCA mutation associated triple negative breast cancer
Authors: Prochaska LH , Godwin AK , Kimler BF , Lehn C , Klemp JR , O'Dea A , Elia M , Hoffmann MS , Crane G , McKittrick R , Sheehan M , Graff SL , Madhusudhana S , Khan QJ , Jensen RA , Sharma P 
Published: March 2017

Abstract
Introduction: Pathological complete response (pCR) in unselected triple negative breast cancer (TNBC) is associated with excellent long-term survival. However, controversy remains as to whether pCR in BRCA mutation associated (BRCA[+]) TNBC is predictive of improved long-term outcome. A recent study suggests that pCR was not a surrogate for outcomes in BRCA1 associated TNBC. All of the patients in this study harbored an Ashkenazi Jewish founder BRCA1 mutation and the majority of mutation carriers underwent lumpectomy. Impact of pCR as it relates to BRCA status in a larger, heterogeneous TNBC cohort treated in a contemporary time frame is not known.
Aim: Evaluate and compare the prognostic impact of pCR as it relates to the BRCA mutation status in patients enrolled in a prospective multisite TNBC registry.
Methods: 453 patients with stage I-III TNBC were enrolled within a multisite registry between 2011- 2015, out of which 173 received neoadjuvant chemotherapy (NAC) and also underwent germline BRCA testing. pCR in the breast and axilla was evaluated and patients were followed for reoccurrence and survival. Recurrence free survival (RFS) was estimated according to the Kaplan-Meier method and compared among groups with log-rank statistic.
Results: For the 173 eligible patients the median age was 49 years; African-American:14%; median tumor size:3 cm; 42%:Lymph node positive; and 18% (32/173) demonstrated BRCA mutation (BRCA1=28, BRCA2=4). All patients received anthracycline and/or taxane based NAC. pCR rates for BRCA[+] and wild type (BRCA[-]) patients was 72% and 46% respectively (p=0.01). 97% of BRCA[+] and 42% of BRCA[-] patients underwent bilateral mastectomy (p=0.001). The three year RFS was 92% and 81% in BRCA[+] and BRCA[-] patients, respectively (p=0.18). Attainment of pCR was associated with excellent 3 year RFS of 95% and 97% in BRCA[+] and BRCA[-] patients, respectively (p=0.85). Among BRCA[-] patients lack of pCR was associated with significantly worse 3 year RFS (70% RFS in patients without pCR, compared to 97% in patients with pCR; p=0.001). Among BRCA[+] patients lack of pCR was associated with numerically lower but not statistically significant worse 3 year RFS (83% RFS in patients without pCR, compared to 95% in patients with pCR; p=0.41). On multivariable Cox regression analysis, only stage III disease was associated with higher risk of relapse (p&lt;0.001).
Conclusions: Our observation of higher pCR in BRCA-carriers compared to wild-type TNBC patients is consistent with previously published literature. In this contemporary cohort of TNBC patients for whom the majority of BRCA[+] patients underwent bilateral mastectomy, attainment of pCR carried an excellent prognosis in both BRCA[+] and BRCA[-] patients. On the other hand, BRCA[+] patients who do not attain pCR may have better outcomes compared to BRCA[-] patients without pCR. Further research to explore the underlying biological mechanisms involved in tumor response and relapse in BRCA[+] and BRCA[-] TNBC patients is needed. Furthermore, given these observations, germline BRCA mutation status should be used as a stratification variable in studies evaluating pCR and long term outcomes with investigational therapies in TNBC.
Citation Format: Prochaska LH, Godwin AK, Kimler BF, Lehn C, Klemp JR, O'Dea A, Elia M, Hoffmann MS, Crane G, McKittrick R, Sheehan M, Graff SL, Madhusudhana S, Khan QJ, Jensen RA, Sharma P. Pathological complete response is associated with excellent outcomes in BRCA mutation associated triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-02.