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Review
. 2023 Feb 20;15(4):1346.
doi: 10.3390/cancers15041346.

Prognostic and Predictive Biomarkers in Familial Breast Cancer

Siddhartha Deb  1   2 , Anannya Chakrabarti  3 , Stephen B Fox  4
Affiliations
Review

Prognostic and Predictive Biomarkers in Familial Breast Cancer

Siddhartha Deb et al. Cancers (Basel). .

Abstract

Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. While there is extensive research and data accrued on risk stratification and genetic predisposition, there are few data pertaining to relevant prognostic and predictive biomarkers within this breast cancer subgroup. The following is a review of such biomarkers in male and female familial breast cancer, although the data for the former are particularly sparse.

Keywords: BRCA1; BRCA2; biomarker; familial breast cancer; prognostic and predictive.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of PARP, with repair of single-strand DNA break through PARPylation and recruitment of repair proteins of the X-ray repair cross-complementing protein 1 (XRCC1) complex. Inhibition of PARP leads to double-strand breaks, which may be repaired by HRR proteins if proficient, or apoptosis in HR-deficient cells. PARPi may occur through multiple mechanisms, including efflux of the inhibitor, mutation of PAPRP affecting trapping, reversion of HRR function or through RAD51-mediated repair, with potential biomarkers highlighted (in red).
Figure 2
Figure 2
PD-L1 inhibitors currently studied in breast cancer, including those approved by the FDA for use in TNBC (*). Scoring schematics demonstrate counting methodology for tumour proportion score (TPS—percentage of tumour staining positively), immune score (IC—percentage of immune cells staining positively) and combine proportion score (CPS—percentage of tumour and immune cells staining positively) with patient immunohistochemical staining of tumour cells (22C3) and TILs (SP142) present.
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References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Claus E.B., Risch N., Thompson W.D. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am. J. Hum. Genet. 1991;48:232–242. - PMC - PubMed
    1. Newman B., Austin M.A., Lee M., King M.C. Inheritance of human breast cancer: Evidence for autosomal dominant transmission in high-risk families. Proc. Natl. Acad. Sci. USA. 1988;85:3044–3048. doi: 10.1073/pnas.85.9.3044. - DOI - PMC - PubMed
    1. Turner N.C., Reis-Filho J.S. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006;25:5846–5853. doi: 10.1038/sj.onc.1209876. - DOI - PubMed
    1. Deb S., Jene N., Fox S.B. Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas. BMC Cancer. 2012;12:510. doi: 10.1186/1471-2407-12-510. - DOI - PMC - PubMed

Grants and funding

This research received no external funding.