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

Overview

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

Detailed description

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.

Primary outcome measures

• 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 [Time frame: 10 years since enrolment]

Secondary outcome measures (3)

• To evaluate the clinico-radiological follow-up (type and frequency) of women with a germline deleterious mutation in BRCA1-2 with or without a history of early breast cancer [Time frame: 10 years since enrolment]
• To evaluate the treatment of early and/or advanced breast cancer in women with a germline deleterious mutation in BRCA1-2 [Time frame: 10 years since enrolment]
• To evaluate disease-free survival and/or progression-free survival and overall survival of women with a germline deleterious mutation in BRCA1-2 treated for early and/or advanced breast cancer [Time frame: 10 years since enrolment]

Eligibility criteria

Inclusion criteria

Cohort A (Retrospective):

• Female sex
• Age ≥ 18 years
• Signed informed consent
• 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
• Admission to the participating Center since 1st of January 2010, prior to site activation

Cohort B (Prospective):

• Female sex
• Age ≥ 18 years
• Signed informed consent
• 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
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 12 centers

• Centro di Riferimento Oncologico - Aviano — Aviano
• IRCCS AOU San Martino, IST Genova — Genova
• Azienda Ospedaliera Papardo — Messina
• ASST Ovest Milanese — Milan
• Azienda ospedaliera Universitaria di Modena — Modena
• Università degli studi di Napoli Federico II — Naples
• Azienda AUSL IRCCS - Reggio Emilia — Reggio Emilia
• ASL Roma 1, Santo Spirito — Roma
• … and 4 more centers

Publications

• Paul A, Paul S. The breast cancer susceptibility genes (BRCA) in breast and ovarian cancers. Front Biosci (Landmark Ed). 2014 Jan 1;19(4):605-18. doi: 10.2741/4230. PMID 24389207
• King MC, Marks JH, Mandell JB; New York Breast Cancer Study Group. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003 Oct 24;302(5645):643-6. doi: 10.1126/science.1088759. PMID 14576434
• Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC; BRCA1 and BRCA2 Cohort Consortium; McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre PMID 28632866
• Rebbeck TR, Mitra N, Wan F, Sinilnikova OM, Healey S, McGuffog L, Mazoyer S, Chenevix-Trench G, Easton DF, Antoniou AC, Nathanson KL; CIMBA Consortium; Laitman Y, Kushnir A, Paluch-Shimon S, Berger R, Zidan J, Friedman E, Ehrencrona H, Stenmark-Askmalm M, Einbeigi Z, Loman N, Harbst K, Rantala J, Melin B, Huo D, Olopade OI, Seldon J, Ganz PA, Nussbaum RL, Chan SB, Odunsi K, Gayther SA, Domchek SM, PMID 25849179
• Carbine NE, Lostumbo L, Wallace J, Ko H. Risk-reducing mastectomy for the prevention of primary breast cancer. Cochrane Database Syst Rev. 2018 Apr 5;4(4):CD002748. doi: 10.1002/14651858.CD002748.pub4. PMID 29620792
• Heemskerk-Gerritsen BA, Menke-Pluijmers MB, Jager A, Tilanus-Linthorst MM, Koppert LB, Obdeijn IM, van Deurzen CH, Collee JM, Seynaeve C, Hooning MJ. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis. Ann Oncol. 2013 Aug;24(8):2029-35. doi: 10.1093/a PMID 23576707

Identifiers

NCT: NCT05835739 · CRO-2019-33

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗