Triple negative breast cancer (TNBC) is a highly aggressive form of breast cancer (BC), accounting for 15% to 20% of cases. It is characterized by estrogen- and progesterone receptor-negative (ER-/PR-) and human epithelial growth factor receptor-2 (HER-2) negative disease. This receptor profile makes treatment difficult. Therapy in early TNBC (eTNBC) generally consists of chemotherapy with an anthracycline and taxane.

Platinum agents (i.e., carboplatin and cisplatin) have a significant role in the management of mTNBC. They have been shown to improve time to progression or progression-free survival. They may also have a small benefit in overall survival (OS) in mTNBC.

TNBC harbors a high percentage of homologous DNA recombination defects from BRCA mutations and other mechanisms. In DNA recombination defects, there is a lack of repair of double-strand breaks in DNA, resulting in failure of the development of a functional DNA molecule.

Platinum agents are very active in cancer cells with DNA repair deficiency, which may account for their beneficial role in mTNBC. However, it is unclear if platinum agents offer any benefit in eTNBC.

Investigators conducted a meta-analysis of prospective randomized, controlled trials to evaluate the role of platinum-based regimens on survival and to assess the toxicities of platinum-based regimens in eTNBC. A search was conducted through March 15, 2021, of Embase, PubMed, the Cochrane Library, the National Institute of Health (, and international conferences for articles.

The search included patients with stages I through III TNBC, those which had at least two arms (a platinum-free and a platinum-containing regimen), and for those which survival data were available. Review articles, meta-analyses, retrospective and observational studies, single-arm studies, and those without survival data were excluded.

Seven articles were included in the meta-analysis, which consisted of 2,027 eTNBC patients (1,007 patients on a platinum-free regimen and 1,020 patients on a platinum-containing regimen). In platinum-based regimens, platinum was either added to standard anthracycline and taxane regimens or was combined with taxane regimens only.

These strategies were utilized in four and three trials involving 981 and 1,046 patients, respectively. In four trials, platinum was administered as neoadjuvant therapy, whereas, in the other three trials, it was given as adjunctive treatment. The median follow-up time ranged from 39 to 79 months.

The efficacy and safety of platinum-based regimens in eTNBC were assessed. The summarized hazard ratio (HR) for disease-free survival (DFS) for the seven trials showed a 30% benefit in favor of the platinum regimens (HR 0.70; 95% CI 0.58-0.84). There was also a trend to improved OS in the platinum-treated groups (pooled HR = 0.78; 95% CI 0.61-1.00). Similar findings were observed when one of the studies, which was confounded by the administration of oral metronomic chemotherapy, was excluded.

A subanalysis was conducted of the two types of platinum regimens. Investigators found that in regimens in which platinum was added to standard anthracycline and taxane protocols, the addition of platinum significantly improved DFS by 34% (HR = 0.66; 95% CI 0.52-0.85). However, it did not affect OS (HR = 0.88, 95% CI 0.62-1.26).

In the group in which platinum was combined with taxane regimens only, there was a trend towards better DFS (HR = 0.75, 95% CI 0.56-1.01); however, there was no effect on OS (HR = 0.8, 95% CI 0.52-1.23). For DFS, it did not matter whether patients were lymph node positive or negative.  Benefit was seen in DFS whether platinum was administered as neoadjuvant therapy (pooled HR = 0.67, 95% CI 0.51-0.88) or as adjuvant therapy (pooled HR 0.72, 95% CI 0.56-0.93).  

Since the safety of anthracycline, taxane, and platinum regimens had been previously evaluated and found to be associated with a significant risk of grade 3 and 4 adverse events, the investigators focused on the adverse event profile of the taxane and carboplatin regimens. They found that this latter group was associated with less overall risk of adverse events, in particular grade 3 and 4 hematologic adverse events and grade 3 and 4 gastrointestinal effects (i.e., anorexia, nausea, diarrhea, and abdominal pain) compared with anthracycline, taxane, and platinum regimens; however, it was associated with more anemia and thrombocytopenia.

The authors caution that more studies are needed as this meta-analysis has limitations, including the various anthracycline/taxane regimens that were not standardized and that dose-dense doxorubicin/dose-dense cyclophosphamide/paclitaxel regimes that were not utilized.

As patients with TNBC explore different options to manage their disease, pharmacists who care for these patients should be knowledgeable about various treatment alternatives.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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