Outcome of intensive breast cancer surveillance for initially disease-free BRCA mutation carriers

Abstract

Background/Objective: Pathogenic mutations of the BRCA tumor suppressor genes result in greater lifetime risk for breast cancer; intensive surveillance is recommended unless riskreducing prophylactic mastectomy is performed. This study aimed to evaluate the incidence of breast cancer amongst disease-free BRCA mutation carriers under surveillance, the characteristics of those who subsequently developed breast cancer, and the performance of the screening imaging modalities. Methods: The analysis was performed on a prospectively maintained database of Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2018. Patients with BRCA 1 or 2 pathogenic mutations without a history of breast cancer and prophylactic mastectomy were reviewed. Surveillance program included biannual clinical examination, annual mammogram (MMG) together with ultrasound (USG), and annual magnetic resonance imaging (MRI) with contrast. Mutation carriers were scheduled to have 1 screening imaging every 6 months, with alternating MMG + USG and MRI. Results: During the study period, 410 patients from 260 families were diagnosed with BRCA 1 or 2 mutations. After excluding 276 patients with the diagnosis of breast cancer and 13 patients who died or lost to follow-up before the release of the genetic test results, 121 breast cancer-free patients were included for analysis. Upon detection of pathogenic mutations, all of them chose the intensive surveillance program instead of prophylactic mastectomy; while 8 (6.6%) agreed to have oral chemoprophylaxis. During surveillance, 1 patient later decided to undergo bilateral prophylactic mastectomy, 9 (7.4%) were newly detected with breast cancer. The average annual cancer occurrence rate was 2.8% (28 per 1000 BRCA mutation carriers) during the study period, which was significantly higher compared to the crude incidence rate of 0.106% in the general population from the Hong Kong Cancer Registry (2009 – 2016). The median interval from surveillance to cancer-detection is 35 months. The median age of diagnosis was 43 years old. Seven (77.8%) were diagnosed at Stage 0 or 1. Four patients (44.4%) underwent contralateral prophylactic mastectomy with cancer operation. Regarding imaging modalities, 5 patients (55.6%) were detected by MRI, while the rest (44.4%) were by MMG, USG or the combination. During the surveillance period, 38 patients were noted to have suspicious findings on imaging at least once, and the recall rate was 31.4% Conclusions: Breast cancer incidence is significantly higher in BRCA mutation carriers. While prophylactic mastectomy was not popular among those who were cancer-free in our population, management relied mainly on intensive surveillance. Approximately one-third of the patients would have suspicious findings during surveillance which required further investigations. MRI could be more sensitive in detecting earlier stage cancer than MMG and USG. Cost-effective analysis of intensive breast cancer surveillance in BRCA mutation carriers is warranted.