BETHESDA, Md., May 11, 2021 / PRNewswire / – The American College of Medical Genetics and Genomics (ACMG) has released an important new resource on the clinical practice of a global team of cancer genetics specialists that will help inform the clinical management of patients with increased risk of breast cancer, pancreatic cancer and possibly ovarian cancer.

“The Management of Individuals with Germline Variants in PALB2: A Clinical Practice Resource from the American College of Medical Genetics and Genomics (ACMG)” has been published in the Official Journal of ACMG, Genetics in medicine.

PALB2 (Partner and locator of BRCA2), pathogenic germline variants are associated with a significantly increased risk of breast cancer and a lower increased risk of pancreatic and ovarian cancer. Germline pathogenic / probable pathogenic (P / LP) variants PALB2 were first associated with an increased risk of cancer in 2007 and clinical trials have been available since then. It is now considered the third most important gene in breast cancer after BRCA1 and BRCA2. Despite the emerging importance of this gene, there has been a dearth of resources to guide the clinical management of women and men with PALB2 germ line P / LP variants.

“PALB2 is sometimes called “BRCA3”, given its importance in the risk of breast cancer. People who harbor a pathogenic or possibly pathogenic variant of the germ line PALB2 face difficult questions, especially about their personal risk of developing breast, ovarian and pancreatic cancers, and how to manage that risk. In developing this clinical practice resource, we have sought to help patients and their care providers make the best possible decisions based on current, high-quality, peer-reviewed evidence and a global network of medical practitioners with a expertise in cancer genetics, ”said Douglas R. Stewart, MD, FACMG, co-author and past chair of the ACMG Professional Practice and Guidelines Committee.

The main recommendations are as follows:

• Personalized risk estimates (eg, CanRisk) should be used to guide clinical management.
• PALB2 SUV (variants of uncertain significance) should not be used to guide clinical management.
• Prospective collection of clinical data PALB2 patients should be used to establish clear parameters on treatment outcome and survival.
• PALB2 patients should receive similar monitoring BRCA1 / 2, modified according to individual risk.
• A risk-reducing mastectomy may be considered an option, guided by personalized risk assessments.
• Surveillance for pancreatic cancer can be considered in the context of a family history, ideally as part of a clinical trial.
• Ovarian cancer surveillance should not be offered; Salpingo-oophorectomy (surgery to remove the ovaries and fallopian tubes) should include shared decision-making and should rarely be considered before the age of 50.
• Given the mechanistic similarities, PALB2 patients can be considered for treatment regimens and trials such as those for BRCA1 / 2.
• ACMG does not recommend testing partners of PALB2 patients in the process of childbearing, unless this can be justified by the partner’s family history of cancer.

This clinical practice resource concludes that this advice is similar to that of patients with BRCA1 / 2. While the range of cancer risk estimates overlaps BRCA1 / 2, it’s lower in PALB2, individualized estimates are therefore important for management decisions. Systematic collection of prospective data is needed to determine, to date, unanswered questions, such as risk of contralateral breast cancer and survival after cancer diagnosis.

“This new document is an important milestone for ACMG in many ways,” said Marc S. Williams, MD, FAAP, FACMG, FACMI, President of the American College of Medical Genetics and Genomics. “First, it reflects ACMG’s commitment to develop guidelines for the use of germline genetic information for the treatment of cancer patients. Second, it represents the first of what we hope will be many guidance documents reflecting a diverse global perspective. The working group included experts on PALB2 around the world so that the advice is relevant to patients of diverse backgrounds receiving care in diverse settings, ”he said.

The global team of authors for this new clinical practice resource includes Marc Tischkowitz, MD, PhD, Judith Balmana, MD, PhD, William D. Foulkes, MBBS, PhD, Paul James, MD, PhD, Joanne ngeow, MBBS, MPH, Rita schmutzler, MD, Nicoleta Voian, MD, MPH, Myra J. Wick, MD, PhD, Douglas R. Stewart, MD and Tuya Pal, MD and the Professional Practice and Guidelines Committee of ACMG. They are experts in clinical cancer genetics, breast and gynecological surgery, and medical oncology and practice in Australia, Asia, United States, Canada, the UK and Europe.

About the American College of Medical Genetics and Genomics (ACMG) and the ACMG Foundation

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical professional organization solely dedicated to improving health through the practice of medical genetics and genomics, and the only medical specialty company in the United States that represents the full spectrum of medical genetics disciplines in a single organization. ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice to over 2,500 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are certified in the specialties of medical genetics. The mission of ACMG is to improve health through clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and of genomics throughout medicine and public health care. Four overarching strategies guide the work of ACMG: 1) to strengthen and expand ACMG’s position as a leading and leading authority in the field of medical genetics and genomics, including clinical research , while educating the medical community about the important role genetics and genomics will continue to play. play to understand, prevent, treat and cure diseases; 2) securing and expanding the professional workforce in medical genetics and genomics; 3) defend the specialty; and 4) provide best-in-class education to members and non-members. Genetics in Medicine, published monthly, is the official journal of ACMG. ACMG’s website, www.acmg.net, offers resources including policy statements, practice guidelines, educational programs and a “Find a Genetic Service” tool. ACMG’s educational and public health programs depend on charitable donations from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Contact: Kathy moran, MBA
[email protected]

SOURCE American College of Medical Genetics and Genomics

Related links

www.acmg.net