Τίτλος:
Article chek2 pathogenic variants in greek breast cancer patients: Evidence for strong associations with estrogen receptor positivity, overuse of risk-reducing procedures and population founder effects
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
CHEK2 germline pathogenic variants predispose to breast cancer and possibly to other malignancies, with their spectrum and frequency being variable among populations. The majority of CHEK2-associated breast tumors are hormone receptor positive; however, relevant clinical outcomes are not well defined. Herein, we illustrate the histopathological characteristics and clinical outcomes of 52 Greek breast cancer patients who are CHEK2 carriers. Genetic analysis was performed by Sanger/massively parallel sequencing, followed by MLPA. Subsequent haplotype analysis investigated possible founder effects. Blood relatives were offered cascade testing. CHEK2 variant spectrum was characterized by variability, while influenced by founder effects. The majority of carriers, i.e., 60.8%, were diagnosed with breast cancer before the age of 45. Notably, 91.5% of breast tumors were hormone receptor positive. Hormone therapy and mastectomy at diagnosis seem to have a positive trend on overall survival, after a median follow-up of 9.5 years. Remarkably, 41.9% of patients underwent risk-reducing surgery, one third of which involved salpingo-oophorectomy. Nearly half of families responded to cascade testing. Our data highlight the need for guideline-adherent choices, based on the evidence that CHEK2 carriers are at moderate risk for breast cancer and no risk for ovarian cancer, while underscore the possible role of chemoprevention with tamoxifen. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Apostolou, P.
Dellatola, V.
Papadimitriou, C.
Kalfakakou, D.
Fountzilas, E.
Faliakou, E.
Fountzilas, G.
Romanidou, O.
Konstantopoulou, I.
Fostira, F.
Περιοδικό:
Blood cancer journal
Λέξεις-κλειδιά:
checkpoint kinase 2; estrogen receptor, adult; Article; breast cancer; breast carcinoma; breast carcinoma in situ; cancer hormone therapy; cancer patient; cancer risk; CHEK2 gene; clinical outcome; cohort analysis; controlled study; ductal carcinoma; estrogen receptor positive breast cancer; family history; female; follow up; founder effect; genetic variability; Greek (people); haplotype; heterozygote; histopathology; human; human tissue; intraductal carcinoma; lobular carcinoma; lumpectomy; major clinical study; male; massively parallel signature sequencing; mastectomy; missense mutation; multiplex ligation dependent probe amplification; overall survival; pathogenicity; progesterone receptor positive breast cancer; prophylactic mastectomy; relative; risk reduction; salpingooophorectomy; Sanger sequencing; triple negative breast cancer
DOI:
10.3390/cancers13092106
