Search

Studies conducted primarily among European ancestry women reported 12 breast cancer predisposition genes. However, etiologic roles of these genes in breast cancer among African ancestry women have been less well-investigated.We conducted a case-control study in African American women, which included 1117 breast cancer cases and 2169 cancer-free controls, and a pooled analysis, which included 7096 cases and 8040 controls of African descent. Odds ratios of associations with breast cancer risk were estimated.Using sequence data, we identified 61 pathogenic variants in 12 breast cancer predisposition genes, including 11 pathogenic variants not yet reported in previous studies. Pooled analysis showed statistically significant associations of breast cancer risk with pathogenic variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, TP53, NF1, RAD51C, and RAD51D (all P.05). The associations with BRCA1, PALB2, and RAD51D were stronger for estrogen receptor (ER)-negative than for ER-positive breast cancer (P heterogeneity.05), whereas the association with CHEK2 was stronger for ER-positive than for ER-negative breast cancer.Our study confirmed previously identified associations of breast cancer risk with BRCA1, BRCA2, PALB2, ATM, TP53, NF1, and CHEK2 and provided new evidence to extend the associations of breast cancer risk with RAD51C and RAD51D, which was identified previously in European ancestry populations, to African ancestry women.

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.

Individuals carrying deleterious germline mutations placing them at increased risk for hereditary cancer syndromes (high-risk consumers) often have a great deal of fear and concern over transmitting mutations to their offspring, particularly conditions which are autosomal dominant. Preimplantation genetic diagnosis (PGD) is a procedure that can detect certain germline cancer predisposing mutations present in embryos. The objective of this review was to assess high-risk consumers' knowledge and perceptions of PGD for hereditary cancers. A systematic literature review was conducted through PubMed, Wiley Interscience, PsychInfo, and Cochrane Library databases to identify all articles assessing consumer knowledge and attitudes of PGD for hereditary cancer syndromes. We assessed heterogeneity and the robustness of findings through additional analyses according to study location, hereditary cancer type, and sample size. Thirteen articles remained eligible after the application of specific criteria. Results show a general low level of knowledge about PGD for hereditary cancers, moderate rates of acceptability among high-risk groups, and high levels of need for information about PGD. Individuals in specific risk groups such as those with a personal or family history of hereditary breast and ovarian cancer (HBOC) syndrome or familial adenomatous polyposis (FAP) may benefit from educational information from healthcare professionals about the use of PGD.