Abstract PD10-06: Clinical behavior and outcomes of <i>BRCA</i>-mutated breast cancer in young patients according to type of <i>BRCA</i> mutation and hormone receptor status: Results from an international cohort study

Abstract Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p<0.001). Compared to mBRCA2 breast cancer pts, those with mBRCA1 were younger, more likely to have reported Jewish ancestry, had more grade 3 tumors, less nodal involvement, lobular histology and HER2 positivity, and received more frequently chemotherapy (all p<0.001). More mBRCA1 pts with hormone receptor-positive tumors did not receive adjuvant endocrine therapy (14.7% vs. 4.2%, p<0.001). No difference between mBRCA1 and mBRCA2 pts was observed in risk-reducing mastectomy (43.9% vs. 46.0%; p=0.371) or salpingo-oophorectomy (48.3% vs. 48.8%; p=1.0). Median follow-up was 7.9 years (range 5.6-10.6 years). Second primary breast cancers (17.0% vs. 12.2%, p=0.025) and non-breast primary malignancies (4.3% vs. 1.9%, p=0.033) were more frequent among mBRCA1 pts compared to mBRCA2 pts, while distant recurrences were less frequent (10.4% vs. 15.4%, p=0.013). 8-year DFS was 62.8% and 65.9% for mBRCA1 and mBRCA2 pts, respectively (adjusted HR 0.76; 95% CI 0.60-0.96). The worse DFS in mBRCA1 was observed regardless of hormone receptor status (pinteraction=0.848): hormone receptor-positive (adjusted HR 0.77; 95% CI 0.58-1.03) and hormone receptor-negative (adjusted HR 0.73; 95% CI 0.48-1.13). No differences in DRFI and OS were observed between mBRCA1 and mBRCA2 pts. Compared to pts with hormone receptor-negative disease, those with hormone receptor-positive breast cancer had higher chances of developing distant (± loco-regional) recurrences (16.1% vs. 9.0%; p<0.001) and less frequent second primary malignancies (BC: 12.1% vs. 17.9%, p=0.005; non-BC: 2.8% vs. 4.0%, p=0.216). No differences in DFS and OS were observed between pts with hormone receptor-positive or negative breast cancer. However, there was a trend towards worse DRFI in women with hormone receptor-positive breast cancer as compared to those with hormone receptor-negative disease (8-year DRFI: 83.4% vs. 90.1%; adjusted HR 1.39; 95% CI 0.94-2.05). Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

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