Universität zu Köln

Tischkowitz, Marc, Balmana, Judith, Foulkes, William D. ORCID: 0000-0001-7427-4651, James, Paul ORCID: 0000-0002-4361-4657, Ngeow, Joanne, Schmutzler, Rita, Voian, Nicoleta, Wick, Myra J., Stewart, Douglas R. and Pal, Tuya (2021). Management of individuals with germline variants in PALB2: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet. Med., 23 (8). S. 1416 - 1424. LONDON: SPRINGERNATURE. ISSN 1530-0366

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Abstract

Purpose PALB2 germline pathogenic variants are associated with increased breast cancer risk and smaller increased risk of pancreatic and likely ovarian cancer. Resources for health-care professionals managing PALB2 heterozygotes are currently limited. Methods A workgroup of experts sought to outline management of PALB2 heterozygotes based on current evidence. Peer-reviewed publications from PubMed were identified to guide recommendations, which arose by consensus and the collective expertise of the authors. Results PALB2 heterozygotes should be offered BRCA1/2-equivalent breast surveillance. Risk-reducing mastectomy can be considered guided by personalized risk estimates. Pancreatic cancer surveillance should be considered, but ideally as part of a clinical trial. Typically, ovarian cancer surveillance is not recommended, and risk-reducing salpingo-oophorectomy should only rarely be considered before the age of 50. Given the mechanistic similarities, PALB2 heterozygotes should be considered for therapeutic regimens and trials as those for BRCA1/2. Conclusion This guidance is similar to those for BRCA1/2. While the range of the cancer risk estimates overlap with BRCA1/2, point estimates are lower in PALB2 so individualized estimates are important for management decisions. Systematic prospective data collection is needed to determine as yet unanswered questions such as the risk of contralateral breast cancer and survival after cancer diagnosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tischkowitz, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Balmana, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Foulkes, William D. UNSPECIFIED orcid.org/0000-0001-7427-4651 UNSPECIFIED James, Paul UNSPECIFIED orcid.org/0000-0002-4361-4657 UNSPECIFIED Ngeow, Joanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Voian, Nicoleta UNSPECIFIED UNSPECIFIED UNSPECIFIED Wick, Myra J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stewart, Douglas R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pal, Tuya UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-603027
DOI:	10.1038/s41436-021-01151-8
Journal or Publication Title:	Genet. Med.
Volume:	23
Number:	8
Page Range:	S. 1416 - 1424
Date:	2021
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	1530-0366
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BREAST-CANCER RISK; RECOMBINATION REPAIR; FANCONI-ANEMIA; MUTATIONS Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60302