Platinum-based chemotherapy in triple-negative advanced breast cancer

Abstract

The purpose of this study was to evaluate the efficacy of platinum-based chemotherapy (PBC) versus conventional non-PBC regimens in a metastatic triple-negative breast cancer (TNBC) setting. We reviewed the electronic patient records of patients with confirmed metastatic TNBC at four major cancer centres in Canada. All patients were allocated into two groups based on type of chemotherapy received (PBC vs. non-PBC) and line of treatment (first-, second-, or third-line). The primary objective of this study was to evaluate the efficacy of PBC in metastatic TNBC in terms of median duration of overall survival (OS) from diagnosis of distant metastatic disease and compare it with the efficacy of conventional non-platinum-based chemotherapy in metastatic TNBC after controlling for known prognostic factors. A total of 153 metastatic TNBC patients were identified, 58 treated with PBC and 95 with non-PBC. The median time in first-line PBC versus non-PBC was not different between the two groups (2 vs. 2 months, p = 0.9), the median time on treatment in second and third-line therapy was longer for the PBC group compared to the conventional treated group (4 vs. 1 months, p = 0.004; 4 vs. 0.5 months, p = 0.004, respectively). Patients who received PBC had a longer OS compared to those managed conventionally (14.5 vs. 10 months, p = 0.041). This study evaluates the survival outcomes in a homogenous group of TNBC metastatic patients treated with or without PBC. Our results confirmed our hypothesis of a better OS among PBC-treated TNBC patients compared to conventionally managed TNBC patients. Currently ongoing Phase III trials assessing the benefit of PBC versus other chemotherapeutic regimens in advanced TNBC will help define the role of these agents for the management of this breast cancer subtype.

The autophagy inhibitor chloroquine targets cancer stem cells in triple negative breast cancer by inducing mitochondrial damage and impairing DNA break repair

“…Interestingly, many of breast cancer patients with BRCA1 mutations have tumors that are triple-negative and particularly aggressive basal-like subtype [26, 34, 35]. Despite limited efficacy as a single agent in heavily treated metastatic breast cancers [35], carboplatin has shown to be an excellent addition to treatment regimen in TNBC, conferring increasing rates of pathological complete response and survival benefits to patients [13, 14, 36, 37]. Unfortunately, treatment failure is eventually seen in a substantial number of TNBC patients due to chemoresistance over time.…”

Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model

“…Furthermore, ongoing clinical trials for metastatic TNBC are including platinum agents in their treatment regimens (4, 36–38). In an orthotopic humanized breast-to-lung model, treatment with Nutlin-3a/carboplatin significantly inhibited primary tumor growth, and metastatic foci in the lung were fewer in number and smaller in size relative to treatment with vehicle or single-agent therapy.…”

“…Platinum agents, such as cisplatin and carboplatin, form DNA-platinum adducts resulting in intra- and interstrand DNA crosslinks leading to increased double strand breaks and cell death (3). Clinical studies have indicated that platinum-based therapy can provide enhanced efficacy in TNBC (4, 5). Furthermore, clinical trials are currently evaluating the utility of combination therapies that include carboplatin to specifically treat TNBCs with metastases (NCT01881230, NCT00691379, and NCT01281150; www.clinicaltrials.gov).…”

Platinum-based therapy for triple-negative breast cancer treatment: A meta-analysis

“…Four studies (22)(23)(24)(25) reported that the overall survival (OS) rate was not significantly different between TNBC patients treated with a platinum-based regimen and those treated with a non-platinum-based regimen (P>0.05). So does the disease-free survival (DFS) rate according to three studies (Table II) (22)(23)(24).…”