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Review
. 2023 Feb;37(1):203-224.
doi: 10.1016/j.hoc.2022.08.018.

Systemic Therapy for Hereditary Breast Cancers

Elizabeth J Harvey-Jones  1 , Christopher J Lord  2 , Andrew N J Tutt  3
Affiliations
Free article
Review

Systemic Therapy for Hereditary Breast Cancers

Elizabeth J Harvey-Jones et al. Hematol Oncol Clin North Am. 2023 Feb.
Free article

Abstract

Approximately 5% to 10% of all breast cancers are hereditary; many of which are caused by pathogenic variants in genes required for homologous recombination, including BRCA1 and BRCA2. Here we discuss systemic treatment for such breast cancers, including approved chemotherapeutic approaches and also targeted treatment approaches using poly-(ADP ribose) polymerase inhibitors. We also discuss experimental approaches to treating hereditary breast cancer, including new small molecule DNA repair inhibitors and also immunomodulatory agents. Finally, we discuss how drug resistance emerges in patients with hereditary breast cancer, how this might be delayed or prevented, and how biomarker-adapted treatment is molding the future management of hereditary breast cancer.

Keywords: Biomarkers; Chemotherapy; Drug resistance; Hereditary breast cancer; PARPi.

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Conflict of interest statement

Disclosure E.H.-J. is a clinical PhD fellow funded by Cancer Research UK and AstraZeneca. A.T. is a consultant for AstraZeneca, Merck KGaA, Artios, Pfizer, Vertex, GE Healthcare, Inbiomotion, MD Anderson Cancer Centre; has received grant/research support from AstraZeneca, Myriad, Medivation, and Merck KGaA; and is a stockholder in Inbiomotion. Stands to gain from the use of PARP inhibitors as part of the ICR's “rewards to inventors” scheme. C.J.L. makes the following disclosures: receives and/or has received research funding from: AstraZeneca, Merck KGaA, Artios. Received consultancy, SAB membership or honoraria payments from: Syncona, Sun Pharma, Gerson Lehrman Group, Merck KGaA, Vertex, AstraZeneca, Tango, 3rd Rock, Ono Pharma, Artios, Abingworth, Tesselate, Dark Blue Therapeutics. Has stock in: Tango, Ovibio, Enedra Tx., Hysplex, Tesselate. C.J.L. is also a named inventor on patents describing the use of DNA repair inhibitors and stands to gain from their development and use as part of the ICR “Rewards to Inventors” scheme.

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