Fanconi anaemia due to biallelic loss of BRCA2 (Fanconi anaemia subtype D1) is traditionally diagnosed during childhood with cancer rates historically reported as 97% by 5.2 years. This report describes an adult woman with a history of primary ovarian failure, who was diagnosed with gastrointestinal adenocarcinoma and BRCA2-associated Fanconi anaemia at 23 years of age, only after she suffered severe chemotherapy toxicity. The diagnostic challenges include atypical presentation, initial false-negative chromosome fragility testing and variant classification. It highlights gastrointestinal adenocarcinoma as a consideration for adults with biallelic BRCA2 pathogenic variants with implications for surveillance. After over 4 years, the patient has no evidence of gastrointestinal cancer recurrence although the tumour was initially considered only borderline resectable. The use of platinum-based chemotherapy, to which heterozygous BRCA2 carriers are known to respond, may have had a beneficial anticancer effect, but caution is advised given its extreme immediate toxicity at standard dosing. Fanconi anaemia should be considered as a cause for women with primary ovarian failure of unknown cause and referral to cancer genetic services recommended when there is a family history of cancer in the hereditary breast/ovarian cancer spectrum.
- genetic testing
- medical oncology
- gastrointestinal diseases
- genetic predisposition to disease
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Contributors AG, CM, PGr, TS, CB, CS and PGu provided clinical care to the individual described in this report and input regarding the case description and ongoing management. ET, GH, RJS and ABS provided important input regarding variant classification and laboratory diagnostics. EI was responsible for the initial manuscript draft and ongoing revisions. All authors reviewed the manuscript, provided critical review and approved the final manuscript.
Funding EI received funding from a Fellowship grant from the Cancer Institute, NSW (ID 2018_03). TS received funding support from Sydney Catalyst, University of Sydney, NSW, Australia and Cancer Institute, NSW. ABS is support by an NHMRC Investigator Fellowship (ID 1177524).
Competing interests All authors have completed a conflict of interest disclosure form, with the following disclosures to be reported: TS received a conference travel grant from AstraZeneca and AG has been on advisory boards for AstraZeneca (May 2018) and Pfizer (November 2018) and has presented to a Pharmaceutical Benefits Advisory Committee regarding talazoparib (Pfizer) in November 2019.
Provenance and peer review Not commissioned; externally peer reviewed.