Newsletter Fall 2021

PALB2 : Increasingly Recognized as the Third Most Important Inherited Breast Cancer Gene

In May 2021, a clinical practice resource was released by the American College of Medical Genetics and Genomics (ACMG) from a global team of cancer genetics specialists (see figure) to help guide the care of PALB2 carriers.1 PALB2 is considered the third most important breast cancer risk gene, after BRCA1 and BRCA2, with PALB2 carriers at a substantially higher risk for developing female breast cancer and slightly higher risk for developing both pancreatic and ovarian cancer. Yet despite the emerging importance of the PALB2 gene, there has been a lack of resources to guide care, which this guideline sought to address. This information was more recently highlighted in multiple news outlets, after The New York Times published an article entitled “This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous”2 describing the importance of PALB2 and referencing the ACMG practice resource.

Key recommendations included:

  • Personalized risk estimates (e.g., CanRisk) should be used in guiding clinical management
  • Prospective collection of PALB2 patient clinical data should be used to establish clear metrics on treatment outcome and survival
  • PALB2 patients should be offered similar surveillance to BRCA1/2, modified according to individual risk
  • Risk-reducing mastectomy can be considered as an option guided by personalized risk assessments
  • Pancreatic cancer surveillance may be considered in the context of family history, ideally as part of a clinical trial
  • Ovarian cancer surveillance should not be offered; risk-reducing salpingo-oophorectomy should include shared decision-making and should rarely be considered before age 50
  • Given mechanistic similarities, PALB2 patients may be considered for the same therapeutic regimens & trials as BRCA1/2 patients

1Tischkowitz, et al. Genet Med. 2021 Aug. PMID: 33976419. 2Berger. The New York Times. 2021 Aug.

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