Bethesda, MD – May 11, 2021| The American College of Medical Genetics and Genomics (ACMG) has released an important new clinical practice resource from a global team of specialists in cancer genetics that will help inform the clinical management of patients who are at increased risk of breast cancer, pancreatic cancer and likely ovarian cancer.
“Management of individuals with germline variants in PALB2: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)” was published in ACMG’s official journal, Genetics in Medicine.
PALB2 (Partner and Localizer of BRCA2) germline pathogenic variants are associated with substantially increased breast cancer risk and smaller increased risk for pancreatic and ovarian cancer. Germline pathogenic/likely pathogenic (P/LP) variants in PALB2 were first associated with increased cancer risk in 2007 and clinical testing has been available since then. It has come to be considered as the third most important breast cancer gene after BRCA1 and BRCA2. Despite the emerging importance of this gene, there has been a dearth of resources to guide clinical management of women and men with PALB2 germline P/LP variants.
“PALB2 is sometimes referred to as ‘BRCA3,’ given its importance in risk of breast cancer. People who harbor a germline pathogenic or likely pathogenic variant in PALB2 face challenging questions, especially about their personal risk to develop cancers of the breast, ovaries and pancreas, and how to manage that risk. In developing this clinical practice resource, we sought to help guide patients and their treating providers to make the best possible decisions based on current high-quality peer-reviewed evidence and a worldwide network of practicing physicians with expertise in cancer genetics,” said Douglas R. Stewart, MD, FACMG, author and past chair of the ACMG Professional Practice and Guidelines Committee.
Key recommendations include the following:
• Personalized risk estimates (e.g., CanRisk) should be used in guiding clinical management.
• PALB2 VUS (variants of uncertain significance) should not be used to guide clinical management.
• Prospective collection of clinical data from PALB2 patients 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.
The full document can be accessed here