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

Southey MC, Winship I, Nguyen-Dumont T - Hered Cancer Clin Pract (2016)

Bottom Line: Tens of thousands of women worldwide have now had genetic tests for PALB2 mutations in the context of breast cancer susceptibility.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.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC 3010 Australia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

PALB2: evidence-based translation into practice. Based on the Australian Breast Cancer Family Registry and the Australian context
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Fig1: PALB2: evidence-based translation into practice. Based on the Australian Breast Cancer Family Registry and the Australian context

Mentions: An overview of the pathway to translation of new genetic information related to breast cancer clinical genetics practice is shown in Fig. 1. This figure represents women diagnosed with breast cancer under the age of 40 years with a strong family history of breast and or ovarian cancer (two or more effected first or second degree relatives). Pathogenic mutations in BRCA1 and BRCA2 have been identified in approximately 25 % of these women. The risk associated with carrying these mutations and the clinical outcomes for these women (collectively) have been well characterised and this evidence is used to inform the clinical management of these women and their families [21]. Loss-of-function PALB2 mutations are identified in approximately 2 % of these women [17]. Breast cancer risk associated with carrying a PALB2 loss-of-function mutations is now established but research is urgently needed to extend this knowledge to an understanding of clinical outcomes for carriers. Rare mutations in genes associated with genetic syndromes such as Li-Fraumeni (TP53), Cowden syndrome (PTEN) and hereditary diffuse gastric cancer (CDH1) are also present in this group of women at very low frequency. Specific evidence related to clinical outcomes for breast cancer in these contexts is lacking. Additional breast cancer susceptibility genes including ATM and CHEK2 also require prospective data to provide the evidence-base for clinical decision making around risk management/reduction and treatment options. Several other genes have been identified as candidate breast cancer predisposition genes that require further validation such as FANCM [22] and RECQL [23]. The remaining early-onset breast cancer cases with a strong family history remain the subject of research trying to identify the “missing heritability” of breast cancer via numerous initiatives including COMPLEXO [24].Fig. 1


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

Southey MC, Winship I, Nguyen-Dumont T - Hered Cancer Clin Pract (2016)

PALB2: evidence-based translation into practice. Based on the Australian Breast Cancer Family Registry and the Australian context
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837522&req=5

Fig1: PALB2: evidence-based translation into practice. Based on the Australian Breast Cancer Family Registry and the Australian context
Mentions: An overview of the pathway to translation of new genetic information related to breast cancer clinical genetics practice is shown in Fig. 1. This figure represents women diagnosed with breast cancer under the age of 40 years with a strong family history of breast and or ovarian cancer (two or more effected first or second degree relatives). Pathogenic mutations in BRCA1 and BRCA2 have been identified in approximately 25 % of these women. The risk associated with carrying these mutations and the clinical outcomes for these women (collectively) have been well characterised and this evidence is used to inform the clinical management of these women and their families [21]. Loss-of-function PALB2 mutations are identified in approximately 2 % of these women [17]. Breast cancer risk associated with carrying a PALB2 loss-of-function mutations is now established but research is urgently needed to extend this knowledge to an understanding of clinical outcomes for carriers. Rare mutations in genes associated with genetic syndromes such as Li-Fraumeni (TP53), Cowden syndrome (PTEN) and hereditary diffuse gastric cancer (CDH1) are also present in this group of women at very low frequency. Specific evidence related to clinical outcomes for breast cancer in these contexts is lacking. Additional breast cancer susceptibility genes including ATM and CHEK2 also require prospective data to provide the evidence-base for clinical decision making around risk management/reduction and treatment options. Several other genes have been identified as candidate breast cancer predisposition genes that require further validation such as FANCM [22] and RECQL [23]. The remaining early-onset breast cancer cases with a strong family history remain the subject of research trying to identify the “missing heritability” of breast cancer via numerous initiatives including COMPLEXO [24].Fig. 1

Bottom Line: Tens of thousands of women worldwide have now had genetic tests for PALB2 mutations in the context of breast cancer susceptibility.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.

View Article: PubMed Central - PubMed

Affiliation: Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC 3010 Australia.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus