PALB2: research reaching to clinical outcomes for women with breast cancer

Melissa C. Southey, Ingrid Winship, Tú Nguyen-Dumont

PALB2 has taken its place with bona fide breast cancer susceptibility genes. It is now well established that women who carry loss-of-function mutations in the PALB2 gene are at similarly elevated breast cancer risks to those who carry mutations in BRCA2. Information about PALB2 is now being used in breast cancer clinical genetics practice and is routinely included in breast cancer predisposition gene panel tests. Tens of thousands of women worldwide have now had genetic tests for PALB2 mutations in the context of breast cancer susceptibility. However, prospective data related to the clinical outcomes of PALB2 mutation carriers is lacking and very little information (beyond mutation penetrance) is available to guide current clinical management for carriers (affected and unaffected by cancer). In addition, clinical classification of the vast array of non-loss-of-function genetic variants identified in PALB2 is in its infancy. These are key areas of current research efforts and are important foundations on which to move information about PALB2 into the precision public health arena.