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Review
. 2020 Jun 20:2020:9873954.
doi: 10.1155/2020/9873954. eCollection 2020.

Cancer Surveillance in Healthy Carriers of Germline Pathogenic Variants in BRCA1/2: A Review of Secondary Prevention Guidelines

Boudewijn Dullens  1   2 , Robin de Putter  3 , Matteo Lambertini  4   5 , Angela Toss  6 , Sileny Han  2   7 , Els Van Nieuwenhuysen  2   7 , Toon Van Gorp  2   7 , Adriaan Vanderstichele  2   7 , Chantal Van Ongeval  2   8 , Machteld Keupers  2   8 , Renate Prevos  2   8 , Valerie Celis  2   8 , Jeroen Dekervel  9 , Wouter Everaerts  10 , Hans Wildiers  1   2 , Ines Nevelsteen  2   11 , Patrick Neven  2   7 , Dirk Timmerman  7 , Ann Smeets  2   11 , Ellen Denayer  2   12 , Griet Van Buggenhout  2   12 , Eric Legius  2   12 , Kevin Punie  1   2
Affiliations
Review

Cancer Surveillance in Healthy Carriers of Germline Pathogenic Variants in BRCA1/2: A Review of Secondary Prevention Guidelines

Boudewijn Dullens et al. J Oncol. .

Abstract

Germline pathogenic alterations in the breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase of healthy germline BRCA1/2 mutation carriers who are at increased risk for breast, ovarian, and other BRCA-related cancers. This review aims to give an overview of available screening guidelines for female and male carriers of pathogenic or likely pathogenic germline BRCA1/2 variants per cancer type, incorporating malignancies that are more or less recently well correlated with BRCA1/2. We selected guidelines from national/international organizations and/or professional associations that were published or updated between January 1, 2015, and February 1, 2020. In total, 12 guidelines were included. This review reveals several significant discordances between the different guidelines. Optimal surveillance strategies depend on accurate age-specific cancer risk estimates, which are not reliably available for all BRCA-related cancers. Up-to-date national or international consensus guidelines are of utmost importance to harmonize counseling and proposed surveillance strategies for BRCA1/2 carriers.

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Conflict of interest statement

RdP receives honoraria for advisory board for Astra Zeneca. ML has the advisory role for Roche and receives speaker honoraria from Theramex, Takeda, Roche, and Lilly. AT has the advisory role for Lilly and Roche. CVO, MK, and RP authorize the advisory role for the Belgian Society of Human Genetics guidelines. WE receives honoraria for consulting and speaker fees from Janssen, Astellas, and Bayer. He is a senior clinical researcher of FWO Flanders. HW receives consulting fees and honoraria from Abbvie, Amgen, Ariez International, Astra Zeneca, Biocartes, Celldex Therapeutics, DNA Prime, Janssen-CILAG, Lilly, Novartis, ORION Corporation, Pfizer, The Planning Shop, PUMA Biotechnology, Roche, Sirtex, TRM Oncology, and Vifor Pharma. He also receives travel support from Roche, Pfizer, Nippon Travel Agency, Congress Care, DNA Prime, and Global Teamwork. PN receives honoraria for consultancy and/or advisory roles from Pfizer, Novartis, Eli Lilly, and Roche. He receives research funding from Kom op Tegen Kanker. RdP, ED, GVB, and EL are the co-authors of the Belgian Society of Human Genetics guidelines. KP has the advisory/consultancy role for Astra Zeneca, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Roche, and Vifor Pharma. He also receives speaker fees for Eli Lilly, Mundi Pharma, Novartis, Pfizer, and Roche and receives research funding from Sanofi. He obtains travel support from Astra Zeneca, Novartis, Pfizer, Pharma Mar, and Roche. The other authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic overview of surveillance guidelines for breast cancer in asymptomatic female carriers of (likely) pathogenic BRCA1/2 variants. MRI: magnetic resonance imaging; ESMO: European Society for Medical Oncology; NCCN: National Comprehensive Cancer Network; ACR: American College of Radiology; NICE: National Institute for Health and Care Excellence; ACOG: American College of Obstetricians and Gynecologists; SGO: Society of Gynecologic Oncology; SEOM: Sociedad Espanola de Oncologia Médica; AGO: Arbeitsgemeinschaft Gynäkologische Onkologie; INCa: Institut National du Cancer; NABON: Nationaal Borstkanker Overleg Nederland; BeSHG: Belgian Society of Human Genetics. ∗Or starting 10 years earlier than youngest breast cancer diagnosis in the family. ∗∗Or individualized based on family history if a breast cancer diagnosis is present before age 30. ¥Or starting 5–10 years earlier than the youngest breast cancer diagnosis in the family. §Starting 10 years before the youngest breast cancer diagnosis in the family, but not before 30. ‡Considering breast tomography. ∞Or starting earlier if there is a family history of breast cancer before 30 years. ∑Discussing delaying mammography until 40 years with BRCA1 carriers who undergo annual MRI screening. Considering imaging in case of early breast cancer diagnosis in the family. ˜Mammography at age 30, annual mammography from 30 onwards in case of microcalcifications.
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