Breast Cancer Coverage from Every Angle

PALB2-Associated Risks of Breast and Other Cancers

By: Julia Fiederlein
Posted: Monday, May 18, 2020

According to Mayo Clinic researcher Fergus Couch, PhD, as well as a host of other national and international colleagues, PALB2 pathogenic variants appear to be associated with a predisposition to breast, ovarian, and pancreatic cancers. The results of this study of more than 500 families, published in the Journal of Clinical Oncology, suggest that genetic testing should be offered to all women with breast cancer younger than age 66 to determine whether they have this mutation.

“This change would help identify 98% of women with BRCA1 and BRCA2 mutations, and more than 90% of women with mutations in other predisposition genes...,” Dr. Couch stated in a Mayo Clinic press release.

The investigators analyzed genetic data from 524 families with germline pathogenic variants in PALB2. Cancer-specific relative risks were estimated using complex segregation analysis, in which genetic models were fit into cancer inheritance patterns, and familial genotypes were observed. Relative risks were estimated for female/male breast, ovarian, pancreatic, prostate, colorectal, and all other cancers combined. A relative risk greater than 1.5 indicated increased risk.

The risk of female/male breast, ovarian, and pancreatic cancers was determined to be increased in families with PALB2 pathogenic variants. Estimated relative risks were 7.18, 7.34, 2.91, and 2.37, respectively. PALB2 pathogenic variants were not found to play a role in the predisposition of prostate, colorectal, and all other cancers combined.

Furthermore, in terms of PALB2 as a breast cancer susceptibility gene, the investigators believe that guidelines for germline testing require updating, with an increase in the age for genetic testing for all women diagnosed with breast cancer younger than age 66. They noted that the National Comprehensive Cancer Network recommends women younger than age 46 receive germline testing; however, they think this recommendation may overlook approximately 30% of mutation carriers. The results of this study indicate that the majority of mutation carriers may potentially be identified by adjusting the cutoff age.

Disclosure: For full disclosures of the study authors, visit

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