Abstract P2-01-02: Clinicopathological characteristics, treatment patterns and disease outcomes of germline BRCA1/2 carriers with early stage HER2-negative breast cancer and potential eligibility for adjuvant Olaparib
Authors: Morganti Stefania , Jin Qingchun , Vincuilla Julie , Buehler Ryan , Ryan Sean , Stokes Samantha , Parker Tonia , Mittendorf Elizabeth A. , King Tari , Weiss Anna , Partridge Ann , Bychkovsky Brittany , Curigliano Giuseppe , Tayob Nabihah , Lin Nancy U. , Garber Judy , Tolaney Sara , Lynce Filipa 
Published: March 2023

Background: Approximately 5-10% of early breast cancers (eBC) occur in patients (pts) carrying a germline BRCA1/2 (gBRCA1/2) pathogenic (P) or likely P (LP) variant. In the OlympiA trial, 1-year (yr) adjuvant (adj) olaparib (OLA) improved both invasive disease-free survival (iDFS) and overall survival (OS) in gBRCA carriers with high-risk HER2- eBC. Whether benefit of adj OLA might extend beyond the high-risk population defined by the OlympiA criteria remains to be defined.

Methods: Consecutive pts who underwent surgery for a first diagnosis of eBC at Dana-Farber Brigham Cancer Center between 1/2016 and 8/2021 were identified. Genetic data were retrieved from an institutional dataset to identify gBRCA1/2 P/LP carriers tested through Dana-Farber. Clinicopathological variables, treatment and outcomes were characterized. Eligibility for adj OLA was based on the OlympiA study criteria, as follows: triple-negative BC (TNBC) with ≥pT2 or ≥pN1 prior to adj chemotherapy (ACT) or non-pCR after neo-adj CT (NACT); hormone receptor (HR)+ eBC with ≥4 positive nodes prior to ACT or non-pCR and CPS+EG score ≥3 after NACT.

Results: We identified 188 gBRCA (105 BRCA1, 83 BRCA2) carriers with newly diagnosed HER2- eBC. Median age was 42.5 years and 119 (63%) were premenopausal. Tumor stage, grade and subtype are reported in Table 1. Recurrence Score (RS) was performed on 46 pts, with a median value of 25 (2% 0-10 RS, 52% 11-25 RS, 46% ≥26 RS). 97 pts (52%) received NACT, 55 (29%) ACT only and 36 (19%) did not receive CT. Most pts received both anthracyclines and taxanes, either as NACT (68%) or ACT (53%). 19 (20%) and 8 (8%) received platinum as NACT or ACT, respectively. 4 pts received adj OLA. 43 (44%) pts had a pCR after NACT. The pCR rate was higher in BRCA1 than BRCA2 carriers (52 vs 25%, odds ratio (OR) 3.27, p=0.015) and in pts with TNBC than HR+ eBC (50 vs 32%, OR 2.10, p=0.101). After a median follow up for survival of 37 months, 16 iDFS events were recorded, including 4 second primary tumors (3 ovarian and 1 pancreatic cancer). 3-yr iDFS was 89% (95% CI, 84-95) in the overall cohort, with no significant difference according to BRCA status (BRCA2 vs BRCA1: 85% vs 93%, hazard ratio [HR] 2.65 (95% CI, 0.92-7.63), p=0.071) or tumor subtype (HR+ vs TNBC: 87 vs 93%, HR 1.72 (95% CI, 0.60-4.94), p=0.316). 3-yr relapse-free survival (RFS) was 92% (95% CI, 87-97). 54 (29%) pts were potentially eligible for adj OLA. Eligible pts more frequently had TNBC (67 vs 36%, p&lt; 0.001), higher stage (stage I 9 vs 55%, stage II 63 vs 37%, stage III 28 vs 9%), and grade 3 disease (85 vs 69%, p=0.045), were less likely to have ODX performed (2 vs 34%, p&lt; 0.001), and more likely to have received NACT (83 vs 39%, p&lt; 0.001) and radiation therapy (78 vs 33%, p&lt; 0.001). 3-yr iDFS was 87% and 90% for pts eligible vs not eligible (HR 1.36 (95% CI, 0.49-3.74), p=0.555). 10/16 iDFS events occurred among not eligible pts. 3-yr RFS was lower in eligible pts (87 vs 94%; HR 2.23 (95% CI, 0.72-6.92), p=0.165).

Conclusions: In our cohort, approximately 30% of pts were eligible for adj OLA. 3-yr iDFS was similar between pts eligible and not eligible for adj OLA according to OlympiA criteria. Our findings raise a concern regarding proper selection of all gBRCA carriers who may benefit from adj OLA. Further research is needed to identify additional groups of pts who may benefit from adding OLA to CT in higher risk disease or potentially replacing CT in lower risk settings.

Table 1: Characteristics and outcomes of gBRCA1 vs gBRCA2

Citation Format: Stefania Morganti, Qingchun Jin, Julie Vincuilla, Ryan Buehler, Sean Ryan, Samantha Stokes, Tonia Parker, Elizabeth A. Mittendorf, Tari King, Anna Weiss, Ann Partridge, Brittany Bychkovsky, Giuseppe Curigliano, Nabihah Tayob, Nancy U. Lin, Judy Garber, Sara Tolaney, Filipa Lynce. Clinicopathological characteristics, treatment patterns and disease outcomes of germline BRCA1/2 carriers with early stage HER2-negative breast cancer and potential eligibility for adjuvant Olaparib [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-02.