Platinum Salts in Patients with Breast Cancer: A Focus on Predictive Factors

Abstract

Breast cancer (BC) is the most frequent oncologic cause of death among women and the improvement of its treatments is compelling. Platinum salts (e.g., carboplatin, cisplatin, and oxaliplatin) are old drugs still used to treat BC, especially the triple-negative subgroup. However, only a subset of patients see a concrete benefit from these drugs, raising the question of how to select them properly. Therefore, predictive biomarkers for platinum salts in BC still represent an unmet clinical need. Here, we review clinical and preclinical works in order to summarize the current evidence about predictive or putative platinum salt biomarkers in BC. The association between BRCA1/2 gene mutations and platinum sensitivity has been largely described. However, beyond the mutations of these two genes, several other proteins belonging to the homologous recombination pathways have been linked to platinum response, defining the concept of BRCAness. Several works, here reviewed, have tried to capture BRCAness through different strategies, such as homologous recombination deficiency (HRD) score and genetic signatures. Moreover, p53 and its family members (p63 and p73) might also be used as predictors of platinum response. Finally, we describe the mounting preclinical evidence regarding base excision repair deficiency as a possible new platinum biomarker.

Neoadjuvant Treatment for Triple Negative Breast Cancer: Recent Progresses and Challenges

“…The platinum salts react with DNA inside cells and distort the double helix of DNA inducing single-strand breaks (SSB) and double-strand breaks (DSB). When these damages cannot be efficiently repaired, it results in cell death [28]. These agents have shown activity in cancers with germline BRCA mutation, as BRCA 1/2 proteins have an essential role in repairing DNA damage [29][30][31].…”

Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer

“…Although various anticancer therapeutic agents that can target specific receptors in breast cancer have been developed [ 8 ], TNBC does not respond to hormonal therapies that target HER2 and ER [ 9 ]. In order to overcome the limitations of TNBC therapeutic options, platinum-based compounds, including cisplatin and carboplatin, have been used in therapeutic trials for TNBC, in which they can effectively interfere with DNA replication and related cellular processes [ 10 , 11 , 12 , 13 ]. In addition to the development and application of novel anticancer agents, knowledge of specific TNBC characteristics will provide more options in the selection of therapeutic trials.…”

BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study

“…BRCAness has been investigated as a new therapeutic strategy through its pharmacological induction. Intriguing results suggest that the induction of a BRCA-mutant-like phenotype could be achieved through the epigenetic silencing of BRCA1, enhancing platinum salts' activity and enabling the use of targeted drugs such as PARP inhibitors [31,32]. Based on these trials, we also expect that PARP inhibitors may be key drugs for BRCAness in patients with TNBC after neoadjuvant chemotherapy.…”