Tumor characteristics and prognosis in familial breast cancer

Abstract

BackgroundApproximately 5–10% of breast cancers are hereditary and their biology and prognosis appear to differ from those of sporadic breast cancers. In this study we compared the biological features and clinical characteristics of non metastatic breast cancer in patients with BRCA mutations versus patients with a family history suggesting hereditary breast cancer but without BRCA mutations (BRCA wild type) versus patients with sporadic disease, and correlated these findings with clinical outcome.MethodsWe retrieved the clinical and biological data of 33 BRCA-positive, 66 BRCA-wild type and 1826 sporadic breast cancer patients contained in a single institution clinical database between 1980 and 2012. Specifically, we recorded age, tumor size, nodal status, treatment type, pattern of relapse, second primary incidence, outcome (disease-free survival and overall survival), and biological features (estrogen receptor [ER], progesterone receptor [PgR], tumor grade, proliferation and c-erbB2 status). Median follow-up was 70 months.ResultsBRCA-positive patients were significantly younger than sporadic breast cancer patients, and less likely to be ER-, PgR- or c-erbB2-positive than women with BRCA-wild type or sporadic breast cancer. Tumor size and grade, nodal status and proliferation did not differ among the three groups. Rates of radical mastectomy were 58, 42 and 37%, and those of conservative surgery were 42, 58 and 63% in women with BRCA-positive, BRCA-wild type and sporadic breast cancer (p = 0.03), respectively. The incidence of contralateral breast cancer was 12, 14 and 0% (p <0.0001) and the incidence of second primary tumors (non breast) was 9, 1 and 2% (p <0.0001) in BRCA-positive, BRCA-wild type and sporadic breast cancer, respectively. Median disease-free survival in years was 29 in BRCA-wild type, 19 in BRCA-positive and 14 in sporadic breast cancer patients (log-rank = 0.007). Median overall survival in years was not reached for BRCA-wild type, 19 for BRCA-positive and 13 for sporadic breast cancer patients (log-rank <0.0001). At multivariate analyses only BRCA-wild type status was related to a significant improvement in overall survival versus the sporadic breast cancer group (HR = 0,51; 95% CI (0,28–0,93) p = 0.028).ConclusionsThe biology and outcome of breast cancer differ between patients with BRCA mutations, patients with a family history but no BRCA mutations and patients with sporadic breast cancer.

Effect of Family History on Clinical and Pathological Characteristics of Breast Cancer: a Hospital-Based Study in Egypt

“…As regard tumor size; the present study showed a significantly higher percentage of T4 tumors in patients with positive family history. This disagrees with Arpino et al (25) who found no significant relation between tumor size and familial or sporadic breast cancer. Also, this study reported that bilateral breast cancer was significantly more frequently in the FBC group.…”

Management of patients with BRCA mutation from the point of view of a breast surgeon

“…The type of surgery performed differs significantly, where female with BRCA mutation more often choose mastectomy, a decision made together with their physician. Risk of recurrence and risk of contralateral breast cancer is the same in genetically caused breast cancer with and without BRCA mutation and it is greater than the risk in sporadic cancers [ 29 ].…”

Identification of a novel truncating mutation in PALB2 gene by a multigene sequencing panel for mutational screening of breast cancer risk‐associated and related genes

“…Thirty‐four patients, selected as previously described, and four cell lines, as positive controls, were analyzed in this study. With the aim of identifying gene sequence variations in BC samples from patients with and without BRCA gene mutations, we designed a multigene custom panel including 27 genes specifically involved in DNA damage repair pathways; 50 ng of input DNA was used for library preparation and sequencing as detailed in Material and methods.…”

“…Thirty-four patients, selected as previously described, 17 Globally, the designed test led to the identification of about 40 gene sequence variations, as detailed in Table S2, most of them being already described as BC predisposing ones, including all those previously identified in the same patients by Sanger sequencing of BRCA1 and BRCA2. In particular, we first evaluated sequence quality at the BRCA loci, finding 15 known variations in different patients.…”