Progress and Prospects in Research and Clinical Practice of Hormone Receptor-positive, HER-2-negative Breast Cancer with BRCA1/2 Mutations

Overview

Journal Discov Oncol

Publisher Springer

Specialty Oncology

Date 2023 Jun 23

PMID 37351713

Authors

Shunchao Yan

Murshid Imam

Affiliations

Soon will be listed here.

Abstract

Breast cancer (BC) is a heterogeneous disease that is the most common cancer in women worldwide. However, precise subtyping and corresponding treatments have improved patient outcomes. Hormone receptor (HR)-positive, human epidermal growth factor receptor type 2 (HER2)-negative (HR+/HER2-) BC with BRCA1 and/or BRCA2 mutations (BRCA1/2m) is a unique BC subset with dual drivers: homologous recombination deficiency and hormone receptor signaling. Wild-type BRCA1/2 suppresses estrogen receptor-mediated signaling. Loss-of-function mutations in BRCA1/2 release estrogen receptor suppression, leading to reduced sensitivity to endocrine therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) exert antitumor effects against this subtype and can be used in combination with endocrine therapy. Although PARPis have been evaluated in metastatic triple-negative breast cancer, their efficacy against HR+/HER2- BC has not been clearly established. The present review summarizes recent advances and prospects in the progress of the HR+/HER2-/BRCA1/2m subgroup. As such, this article provides theoretical guidance for future research and promotes the use of PARPis for the treatment of HR+/HER2-/BRCA1/2m BC.

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References

Haricharan S, Bainbridge M, Scheet P, Brown P . Somatic mutation load of estrogen receptor-positive breast tumors predicts overall survival: an analysis of genome sequence data. Breast Cancer Res Treat. 2014; 146(1):211-20. PMC: 4061465. DOI: 10.1007/s10549-014-2991-x. View

Cortesi L, Masini C, Cirilli C, Medici V, Marchi I, Cavazzini G . Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer. BMC Cancer. 2010; 10:90. PMC: 2847959. DOI: 10.1186/1471-2407-10-90. View

Dite G, Jenkins M, Southey M, Hocking J, Giles G, McCredie M . Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst. 2003; 95(6):448-57. DOI: 10.1093/jnci/95.6.448. View

Calvo V, Beato M . BRCA1 counteracts progesterone action by ubiquitination leading to progesterone receptor degradation and epigenetic silencing of target promoters. Cancer Res. 2011; 71(9):3422-31. DOI: 10.1158/0008-5472.CAN-10-3670. View

Krammer J, Pinker-Domenig K, Robson M, Gonen M, Bernard-Davila B, Morris E . Breast cancer detection and tumor characteristics in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2017; 163(3):565-571. PMC: 5490380. DOI: 10.1007/s10549-017-4198-4. View

Fan S, Wang J, Yuan R, Ma Y, Meng Q, Erdos M . BRCA1 inhibition of estrogen receptor signaling in transfected cells. Science. 1999; 284(5418):1354-6. DOI: 10.1126/science.284.5418.1354. View

Thorslund T, West S . BRCA2: a universal recombinase regulator. Oncogene. 2007; 26(56):7720-30. DOI: 10.1038/sj.onc.1210870. View

Mirkovic N, Marti-Renom M, Weber B, Sali A, Monteiro A . Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. Cancer Res. 2004; 64(11):3790-7. DOI: 10.1158/0008-5472.CAN-03-3009. View

Pal T, Cragun D, Lewis C, Doty A, Rodriguez M, Radford C . A statewide survey of practitioners to assess knowledge and clinical practices regarding hereditary breast and ovarian cancer. Genet Test Mol Biomarkers. 2013; 17(5):367-75. PMC: 3634150. DOI: 10.1089/gtmb.2012.0381. View

10.

Fasching P, Link T, Hauke J, Seither F, Jackisch C, Klare P . Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol. 2020; 32(1):49-57. DOI: 10.1016/j.annonc.2020.10.471. View

11.

Valachis A, Nearchou A, Lind P . Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014; 144(3):443-55. DOI: 10.1007/s10549-014-2890-1. View

12.

Lord C, Ashworth A . PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330):1152-1158. PMC: 6175050. DOI: 10.1126/science.aam7344. View

13.

Shah P, Patil S, Dickler M, Offit K, Hudis C, Robson M . Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: Differences based on germline mutation status. Cancer. 2016; 122(8):1178-84. DOI: 10.1002/cncr.29903. View

14.

Fan S, Ma Y, Wang C, Yuan R, Meng Q, Wang J . p300 Modulates the BRCA1 inhibition of estrogen receptor activity. Cancer Res. 2002; 62(1):141-51. View

15.

Rajagopal P, Nielsen S, Olopade O . USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan. JAMA Netw Open. 2019; 2(8):e1910142. DOI: 10.1001/jamanetworkopen.2019.10142. View

16.

Xiang T, Ohashi A, Huang Y, Pandita T, Ludwig T, Powell S . Negative Regulation of AKT Activation by BRCA1. Cancer Res. 2008; 68(24):10040-4. PMC: 2605656. DOI: 10.1158/0008-5472.CAN-08-3009. View

17.

Triantafyllidou O, Vlachos I, Apostolou P, Konstantopoulou I, Grivas A, Panopoulos C . Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece. J BUON. 2015; 20(4):978-84. View

18.

Baretta Z, Mocellin S, Goldin E, Olopade O, Huo D . Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis. Medicine (Baltimore). 2016; 95(40):e4975. PMC: 5059054. DOI: 10.1097/MD.0000000000004975. View

19.

Lewin R, Sulkes A, Shochat T, Tsoref D, Rizel S, Liebermann N . Oncotype-DX recurrence score distribution in breast cancer patients with BRCA1/2 mutations. Breast Cancer Res Treat. 2016; 157(3):511-6. DOI: 10.1007/s10549-016-3836-6. View

20.

Krivokuca A, Mihajlovic M, Susnjar S, Bozovic Spasojevic I, Minic I, Popovic L . Mutational profile of hereditary breast and ovarian cancer - Establishing genetic testing guidelines in a developing country. Curr Probl Cancer. 2021; 46(1):100767. DOI: 10.1016/j.currproblcancer.2021.100767. View