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Review
. 2020 Jul 27:13:227-238.
doi: 10.2147/PGPM.S233485. eCollection 2020.

Comparison of Patient Susceptibility Genes Across Breast Cancer: Implications for Prognosis and Therapeutic Outcomes

Shira Peleg Hasson  1 , Tehillah Menes  2 , Amir Sonnenblick  1
Affiliations
Review

Comparison of Patient Susceptibility Genes Across Breast Cancer: Implications for Prognosis and Therapeutic Outcomes

Shira Peleg Hasson et al. Pharmgenomics Pers Med. .

Abstract

Hereditary breast cancer syndromes affect a small (10-15% of cases) but significant group of patients. BRCA1 and BRCA2 are the most familiar and well-studied genes associated with inherited breast cancer. However, mutations in the high-penetrance genes, TP53, PTEN, CDH1, MSH1, MLH1, MSH6, PMS2, PALB2, and STK11, and in the moderate-penetrance genes, CHEK2, ATM, and BRIP1, also correlate with high lifetime risks of breast cancer and other malignancies as well. Advances in breast cancer genetics have led to an improved perception of diagnosis and screening strategies. The specific considerations and challenges involved in treating this unique population have become a fertile ground for research. Indeed, these genes and downstream molecular pathways have now become potential therapeutic targets in breast cancer patients, including those with BRCA1 or BRCA2 mutations. This review describes the variety of hereditary breast cancer genes, from their molecular origins to the prognosis and multidisciplinary clinical decision-making processes. Key publications and other reported recent clinical trials and guidelines are provided.

Keywords: BRCA; CDH1; Lynch syndrome; PTEN; TP53; breast cancer.

PubMed Disclaimer

Conflict of interest statement

Dr Amir Sonnenblick reports personal fees from Eli lilly, Pfizer, and Roche; grants from Novartis, outside the submitted work. The authors report no other conflict of interest in this work.

Figures

Figure 1
Figure 1
Breast cancer patients with genetic mutations. Approximately 10–15% of breast cancer cases are associated with hereditary syndromes, and the majority of them will carry a deleterious mutation in BRCA1 and BRCA2. Other rare highly penetrant syndromes are Cowden (PTEN) and Li-Fraumeni (p53). After excluding BRCA-positive and syndromic genes, there are pathogenic mutation in other genes.
Figure 2
Figure 2
Breast cancer susceptibility genes and potential therapeutic mechanisms. In Patients with BRCA1/2, PALB2 and BRIP1 mutations, PARPi and platinum should be considered. In patients with PTEN and CDH1 mutations AKT inhibitors in a clinical trial setting may be reasonable. In patients with Lynch syndrome immunotherapy has an emerging role.
See this image and copyright information in PMC

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