inherited breast cancer italian registry a retrospective-prospective observational cohort study to evaluate cancer prevention strategies in women with a deleterious mutation in brca1-2

Conditions: Breast Cancer

Summary: the purpose of the study is to obtain and centralize data about cancer prevention strategies in women with a germline deleterious mutation in brca1-2 with or without a history of breast cancer in italy

women who carry a deleterious mutation in breast cancer susceptibility gene 1 (brca1) or breast cancer susceptibility gene 2 (brca2) have an elevated lifetime risk of developing breast and ovarian cancer, estimated at up to 7 and 25 times that of the average risk population, respectively. by the age of 80 years, the estimated cumulative risk of breast cancer is about 70% for brca1/2 mutation carriers, while the cumulative ovarian cancer risk is about 40% for brca1 and 20% for brca2 carriers. thus, brca1/2 mutation carriers are advised to consider different risk-reducing strategies, including surveillance (breast self-examination, clinical breast examination, screening using mammography, ultrasound and breast magnetic resonance imaging), chemoprevention and prophylactic surgery (prophylactic mastectomy and/or salpingo-oophorectomy). prospective cohort studies demonstrate that risk-reducing mastectomy is associated with 90% or more decreased risk of breast cancer. unfortunately, it is difficult to quantify its effect on overall mortality since no randomized studies have compared risk-reducing mastectomy with enhanced screening, risk-reducing salpingo oophorectomy or prophylactic treatment. additionally, prophylactic mastectomy is an invasive intervention associated with a substantial complication rate and psychological distress, changes in body image and sexual function. therefore, as a preventive measure, risk-reducing mastectomy should be discussed on a case-by case basis, after proper counseling regarding benefits, limitations, risks of surgical complications and psychosocial impact. conversely, risk-reducing salpingo oophorectomy is strongly recommended for women with mutations in brca1 (between ages 35 and 40 years) and brca2 (between ages 40 and 45 years) after completion of childbearing desire, for a significant reduction in ovarian cancer incidence and all-cause mortality. in the absence of solid evidences coming from randomized clinical trials, the aim of the present study is to collect and centralize real-world data on cancer prevention strategies (prophylactic surgery, prophylactic therapies, active surveillance) and oncologic treatments of women with a deleterious mutation in brca1-2 with or without a diagnosis of breast cancer in italy. by collecting and analyzing these data, the identity study aims to obtain a faithful representation of the practices related to oncological surveillance in the group of patients analyzed.

Eligibility criteria:
inclusion criteria: cohort a (retrospective): 1. female sex 2. age ≥ 18 years 3. signed informed consent 4. documented germline deleterious mutation in brca1 and/or brca2 in people with: i) no history of cancer ii) radically treated breast cancer iii) stage iv breast cancer diagnosed after brca1-2 mutation detection 5. admission to the participating center since 1st of january 2010, prior to site activation cohort b (prospective): 1. female sex 2. age ≥ 18 years 3. signed informed consent 4. documented germline deleterious mutation in brca1 and/or brca2 in people with: i) no history of cancer ii) radically treated breast cancer iii) stage iv breast cancer diagnosed after brca1-2 mutation detection 5. admission to the participating center after site activation exclusion criteria: cohort a/b (retrospective/prospective): 1. other malignancies diagnosed within five years prior to brca1-2 mutation detection, except for: * ovarian cancer stage i-ii * basal or squamous cell carcinoma of the skin * melanoma in situ * cis of the cervix