Τίτλος:
Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations. Patients and Methods: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests. Results: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups. Conclusions: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial. © 2019 Elsevier Inc.
The investigation of clinicopathologic characteristics and overall survival of 297 Greek patients with breast cancer carrying pathogenic BRCA1/2 variants revealed known and novel connections. Even though BRCA1- and BRCA2-associated tumors had distinct characteristics, with the latter showing a relatively high predominance for human epidermal growth factor receptor 2-positive tumors, no difference in 15-year overall survival was observed. Our findings provide clinically meaningful observations for BRCA1/2 patients. © 2019 Elsevier Inc.
Συγγραφείς:
Fountzilas, E.
Konstantopoulou, I.
Vagena, A.
Apostolou, P.
Papadimitriou, C.
Christodoulou, C.
Tryfonopoulos, D.
Manousou, K.
Delimitsou, A.
Papamentzelopoulou, M.
Fountzilas, G.
Yannoukakos, D.
Fostira, F.
Περιοδικό:
Clinical Breast Cancer
Εκδότης:
W B SAUNDERS CO-ELSEVIER INC
Λέξεις-κλειδιά:
BRCA1 protein; BRCA2 protein; epidermal growth factor receptor 2; genomic DNA; BRCA1 protein; BRCA1 protein, human; BRCA2 protein; BRCA2 protein, human, adult; Article; breast carcinogenesis; breast tumor; cancer classification; cancer diagnosis; carcinoma; clinical feature; clinical outcome; cohort analysis; colorectal tumor; comparative study; endometrium tumor; esophagus tumor; exon; female; genetic screening; genetic variability; Greece; head and neck tumor; heterozygote; high throughput sequencing; human; immunohistochemistry; in situ hybridization; intron; loss of function mutation; major clinical study; marginal zone lymphoma; multiplex ligation dependent probe amplification; national comprehensive cancer network criteria; ovary tumor; overall survival; pancreas tumor; point mutation; potential difference; Sanger sequencing; second cancer; thyroid tumor; tumor volume; uterine cervix cancer; adjuvant chemotherapy; adjuvant radiotherapy; aged; breast; breast tumor; cancer grading; dna mutational analysis; follow up; genetic predisposition; genetics; Kaplan Meier method; lobular carcinoma; mastectomy; medullary carcinoma; middle aged; mortality; mutation; Paget nipple disease; pathology; retrospective study; second cancer; surgery; treatment outcome; young adult, Adult; Aged; BRCA1 Protein; BRCA2 Protein; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Chemotherapy, Adjuvant; DNA Mutational Analysis; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genetic Testing; Greece; Heterozygote; Humans; Kaplan-Meier Estimate; Mastectomy; Middle Aged; Mutation; Neoplasm Grading; Neoplasms, Second Primary; Radiotherapy, Adjuvant; Retrospective Studies; Treatment Outcome; Young Adult
DOI:
10.1016/j.clbc.2019.08.003
