Abstract PO3-08-03: Comparing prognosis for BRCA1, BRCA2 and non-BRCA breast cancer
Authors: Meireles Pedro Antunes , Bexiga Catarina , Fragoso Sofia , Santos Sidónia , Duarte Teresa , Vaz Fátima 
Published: May 2024

Abstract
BACKGROUND Breast Cancer (BC) is the most diagnosed malignancy and the leading cause of cancer death in women worldwide. Approximately 10% of BC cases are hereditary, and up to 25% have been linked to germline variants of specific genes. Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial BC cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome.
BRCA1 e BRCA2 are tumor suppressor genes, which interact with recombination/DNA repair proteins in pathways that participate in preserving intact chromosome structure, particularly on the DNA double chain. So far, more than 7000 PV were identified on these genes, including the Portuguese founder mutation (BRCA2 c.156_157insAlu), which accounts for a great proportion of BC cases in our country.
BRCA1 and BRCA2 associated BC have distinct clinicopathological characteristics. Long-term follow-up data related to prognosis and survival of either BRCA1 or BRCA2 BC patients is conflicting. Two large meta-analysis report worse overall survival for both, when compared to sporadic BC, whereas two other large meta-analysis concluded on worse overall survival only for BRCA1 patients, with similar overall survival for BRCA2 patients. One meta-analysis reports similar survival for both groups.
We report the analysis of our cohort of BRCA1/2 BC patients included in our multidisciplinary program. Our goal is to compare clinicopathological characteristics and prognosis between BRCA1 and BRCA2 BC and with a control group without germline PV (non-BRCA). METHODS Prospective follow-up was proposed to patients with a diagnosed BRCA1/2 PV. This study included BRCA1/2 patients with BC as first cancer diagnosis, observed between January 2000-May 2023. A control group, with similar phenotype and histological characteristics, without germline PV was used. Statistical analysis was performed to compare characteristics and prognosis between BRCA1 and BRCA2 and non-BRCA BC. ANOVA test was used to compare the age at diagnosis; chi-square was used to compare categorical variables, such as histological subtype and clinical staging at diagnosis; log rank was used to compare the primary and secondary endpoints – overall survival (OS) and invasive disease-free survival (iDFS), respectively. RESULTS From 1077 individuals who tested positive for BRCA1/2 PV, 345 patients had BC, mostly with a BRCA2 PV (66.4%). A control group of 339 individuals was assembled. BRCA2 BC was mostly luminal, as non-BRCA patients, compared with BRCA1 (73.8% vs. 65.8% vs. 25.9%, p&lt; 0.001) and BRCA1 was mostly triple negative, compared with non-BRCA and BRCA2 (65.5% vs. 16.5% vs. 13.3%, p&lt; 0.001). For a mean follow-up time of 10.6 years (±5.6), recurrence was similar, with central nervous system (CNS) metastases being more frequent for BRCA1 (66.7% vs. 23.7% in non-BRCA, and vs. 9.1% in BRCA2, p&lt; 0.001), and bone metastases were predominant for BRCA2 BC (57.5% vs 33.3% in non-BRCA, and vs. 9.1% in BRCA1, p=0.003). Non-BRCA BC showed longer time to recurrence (99.3 months vs. 76.5 months in BRCA2 BC, and vs. 61.2 months in BRCA1 BC, p=0.010), although longer OS was observed in BRCA2 BC (136.2 months vs. 121.7 months in BRCA1 BC, and vs. 113.2 months in non-BRCA, p&lt; 0.001). Development of second primary tumors was more frequent in BRCA2 patients, compared with BRCA1 (20.9% vs 9.2%, p=0.002). DISCUSSION In the Portuguese population, BRCA2 BC is more frequent than BRCA1 BC. Relapses occurred later for BRCA2 BC, affecting mostly the bone, whereas BRCA1 BC relapsed in CNS. As it is stated in the literature, BRCA1 BC is consistent with triple negative, as BRCA2 BC is more associated with luminal subtype. Differences in iDFS favored non-BRCA patients, whereas OS was significantly improved in BRCA2 BC patients. This is the biggest cohort presented in the Portuguese population and one of the biggest presenting BRCA2 BC patients.
Table 1 Characteristics of patients according to BRCA1/2 mutation status (n = 684)
Citation Format: Pedro Antunes Meireles, Catarina Bexiga, Sofia Fragoso, Sidónia Santos, Teresa Duarte, Fátima Vaz. Comparing prognosis for BRCA1, BRCA2 and non-BRCA breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-03.