Results from published studies provide inconsistent levels of evidence for colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) risk in BRCA1 and BRCA2 mutation carriers. For CRC, there is limited evidence to support increased risk in BRCA1 carriers, although the magnitude of risk is very modest and there is no evidence to support increased risk for CRC among BRCA2 carriers. For PDAC, there is evidence to support an approximate 2- to 6-fold increased risk in BRCA2 carriers ascertained from high-risk families, and risk in BRCA1 carriers is less convincing, with some studies reporting no increased risk and others reporting up to a 4-fold increased risk.
Although 2-fold increased risk over the general population conferred by having a first-degree relative with CRC is a criterion for earlier and possibly more intensive screening according to current guidelines, it is not clear that a 1.5-fold increased risk among BRCA1 carriers is sufficient to warrant earlier or more intensive screening. CRC risks in BRCA1/2 carriers are significantly lower than those in individuals with Lynch syndrome, in which risk is increased up to 17-fold. In line with current guidelines, clinicians should consider that BRCA carriers with a first-degree relative with CRC or advanced adenoma should be offered CRC screening at age 40 years, as per current family history–based recommendations, and any carrier with symptoms, such as rectal bleeding or iron deficiency anemia, should be considered for expedited diagnostic evaluation. BRCA carriers without signs or symptoms of CRC and without family history of CRC or advanced adenoma should follow average-risk guidelines for screening until further evidence is available to clarify whether alternate strategies may be warranted.
PDAC screening is less established compared with CRC screening, although emerging evidence is encouraging for early detection. In line with evidence from case-control and cohort studies in high-risk individuals, expert opinion suggests consideration of PDAC screening in BRCA1 and BRCA2 carriers with a family history of PDAC. However, recommendations differ on criterion of the number and degree of affected family members that warrant screening in carriers. At this time, PDAC screening should be performed in a high-volume center preferably in a research setting in order to generate more evidence to support and refine screening in high-risk populations, including BRCA1/2 carriers. Future studies should determine appropriate family history criteria, incorporate risk factors, as well as investigate the role of hemoglobin A1C measurements and novel biomarkers for early PDAC detection.
