Abstract P5-08-10: Surveillance for BRCA1/2 mutation carriers - Is "early detection" really early enough?
Authors: Molho Rinat Bernstein , Kaufman Bella , David Merav A Ben , Sklair-Levy Miri , Laitman Yael , Friedman Eitan 
Published: March 2020

Background: Annual MRI screening is associated with a significant reduction in the incidence of advanced-stage breast cancer (BC) in BRCA1/2 mutation carriers. The purpose of our study was to assess stage at diagnosis and therapeutic approaches in BRCA1/2 carriers and compare these parameters in women who developed BC while adhering to the recommended surveillance scheme ("known carriers"), with BC cases who became aware of their BRCA carreirship after BC diagnosis ("latent carriers").

Methods: Retrospective data were collected on BRCA1/2 mutation carriers treated for BC at the Sheba medical center, both at the oncology institute and the high-risk clinic. The main variables evaluated were tumor characteristics, stage at diagnosis, and treatment decisions.

Results: Overall, 529 BRCA1/2 carriers were identified. At the time of data summary, relevant clinical information was available for 297 patients. Median follow-up time was 77.4 months (range, 2.5-519).

The group of known carriers included 95 women (median age at diagnosis 41.9 [range 27.8-80.3 years]), 70 (74%) were BRCA1 carriers, 23 (24%) BRCA2 carriers, and 2 (2.1%) carried mutations in both genes. The median age at diagnosis of 202 latent carriers was 43.7 (range 23.8-75 years), p=0.8284. Of latent carriers 117 (58%) were BRCA1 mutation carriers and 85 (42%) harbored a BRCA2 mutation.

In the group of known carriers, 19% were diagnosed with carcinoma in situ (DCIS) vs. 5% in the group of latent carriers (p=00012). Stage T1N0 disease was diagnosed in 54/95 (56.8%) of known carriers vs. 59/202 (29.2%) of latent carriers (p&lt;0.00001). Node-positive disease was diagnosed in 11/95 (11.6%) of known carriers vs. 98/202 (48.5%) of latent carriers (p&lt;0.00001). Metastatic disease was diagnosed at presentation in none of the known carriers vs. 4/202 (2%) of latent carriers (p=0.16758).

Overall, in the group of known carriers (including all stages) 46/95 (48.4%) received neoadjuvant (n=12) or adjuvant (n=34) chemotherapy (71.7% of them for triple-negative disease), and 41/95 (43.2%) received radiotherapy. In the group of latent carriers, 162/202 (80.2%) received neoadjuvant (n=74) or adjuvant (n=88) chemotherapy (p&lt;0.00001), 59.3% of them for triple-negative disease, and 173/202 (85.6%) underwent radiotherapy.

Contralateral risk-reducing mastectomy (CRRM) was performed by 59/95 (62%) of the known carriers, 73% of them at the time of primary tumor resection and the rest – at a later stage. Among latent carriers, 82/202 (40.6%) underwent CRRM, 44% at the time of primary tumor resection (p=0.00054).

Conclusions: As expected, diagnosis of early stage disease (DCIS or T1N0) was significantly higher in the group of known BRCA1/2 carriers - disease that was diagnosed in the course of tight surveillance. Yet, despite this early stage diagnosis, chemotherapy and radiotherapy treatments were employed in a substantial proportion of these cases. Healthy BRCA1/2 mutation carriers should be informed about these chemotherapy and radiotherapy rates while discussing risk-reducing surgical options. There is an urgent need for a more accurate ability to predict individual mutation carrier cancer risk, as well as tools for selection of patients with stage I triple-negative disease who will do well without chemotherapy.

Citation Format: Rinat Bernstein Molho, Bella Kaufman, Merav A Ben David, Miri Sklair-Levy, Yael Laitman, Eitan Friedman. Surveillance for BRCA1/2 mutation carriers - Is "early detection" really early enough? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-10.