A population-based study of BRCA breast cancer incidence and prognosis in the Italian Emilia Romagna region: The MUTina study.
Authors: Cortesi Laura , Venturelli Marta , Toss Angela , Barbieri Elena , Musolino Antonino , De Giorgi Ugo , Bisagni Giancarlo , Arcangeli Valentina , Zamagni Claudio , Cavanna Luigi , Dominici Massimo 
Published: June 2023

10616 Background: In Italy, about 3% of all breast cancer (BC) are related to BRCA1 and BRCA2 gene mutations. In the Emilia Romagna Region, a unique hub and spoke model was adopted for select and follow people at risk, starting from the Regional Screening Programs, General Practioners and specialists, covering all the area. This study was designed to uniformly identify and treat BRCA1/2 related BC. Characteristics and outcome of tumors detected by this protocol will be presented. Methods: In this multicenter-retrospective study, seven out of nine provinces collected data about BRCA-related BC identified in the Emilia-Romagna region. Patients and tumors characteristics, surgical information, treatment modalities for early (neoadjuvant or adjuvant therapies) and advanced disease, type of relapse (local/distant), second primary tumors occurrence, surgical preventive strategies (bilateral mastectomy, oophorectomy), gene testing data, disease free survival (DFS) and overall survival (OS) were registered. Comparisons between BRCA1 and BRCA2 tumors were performed. Results: Since 2000 to 2011, 284 BC were registered (171 BRCA1, 110 BRCA2 and 3 BRCA1 and BRCA2 mutated) with a median age at onset of 42 years. BRCA1-related tumors were mostly triple negative BC (TNBC) compared to BRCA2 ones. The diagnosis was at stage I in 52.3% of cases, being 59.7% BRCA1 and 39% BRCA2 (P = 0.0015). BRCA2 patients, compared to BRCA1, received more frequent up-front surgery (85% vs. 74.9%, P = 0.049) and less chemotherapy (34.1% vs 65.9%, P = 0.004). After a median 12-years follow-up period, 136 patients (47,9%) developed an ipsilateral/local or systemic recurrence or contralateral second BC. BRCA1 developed more local recurrences, compared to BRCA2 that had more distant relapses (P = 0.013). Median OS was not reached in the whole population, with 80.3% of patients alive at the analysis cut-off. Among the two populations, there was a benefit trend for BRCA1 patients (P = 0.071), mostly for those who received chemotherapy (P = 0.0036), contralateral mastectomy (P = 0.0001) and oophorectomy (P < 0.0001). Finally, 25.7% of patients developed a second tumor, excluding BC, mostly ovarian cancer. Conclusions: Although BRCA1-related BCs show more aggressive characteristics than BRCA2 BC, the early diagnosis due to our regional surveillance program, leads to a trend for better outcome, even if not statistically significant. The BRCA1 highest rate of recurrence reflects the tendency to local rather than distant relapse. Furthermore, the BRCA deficiency appears to be a predictor of chemosensitivity. Finally bilateral mastectomy and oophorectomy seem to be associated to better outcome. In conclusions, our data support the using of an intensive screening associated to maximal surgery and chemotherapy when BC arises in BRCA carriers, to overcome the unfavorable tumors characteristics of these patients.