Triple-negative breast cancer (TNBC), which is defined as BC lacking expression of estrogen and progesterone receptors and HER-2 receptors, accounts for 12% to 20% of all forms of BC. As it is generally associated with a poorer outcome compared with non-TNBC, various treatment modalities have been explored. Among these treatment options are neoadjuvant (NACT, i.e., chemotherapy delivered before the main treatment) versus adjuvant chemotherapy (ACT, i.e., chemotherapy delivered after the primary treatment). However, which of these treatment options improves outcomes has been unclear.

A recent meta-analysis examining PubMed and Embase databases was conducted to help answer this question. Literature published through January 18, 2020, that specifically focused on patients with a diagnosis of TNBC provided information on survival outcomes between NACT and ACT, assessed overall prognosis of TNBC and reported on survival outcomes was analyzed. Nine articles examining a total of 36,480 patients met these inclusion criteria. The Newcastle-Ottawa quality assessment scale was used to analyze the quality of the nonrandomized studies included in the meta-analysis. Seven of the 9 articles were retrospective and two were prospective.

The investigators found that 29.4% of all patients had received NACT and 70.6% had received ACT. NACT was associated with a pathological complete response (pCR) rate of 35%. Factors associated with achieving pCR included early stage, small tumor, and negative lymph nodes. NACT was associated with a worse overall survival (OS) than ACT, with a 59% greater risk of death (hazard ratio [HR] = 1.59) after 4.12 years of follow-up. Further, those with residual disease (RD) who received NACT had an 18% decrease in OS (HR = 1.18) compared with those who had received ACT.  

Conversely, patients receiving NACT who had achieved pCR had a 47% OS benefit (HR = 0.53) over those who had received ACT. Overall, there was no statistically significant difference between NACT and ACT groups for disease-free survival (DFS) after a median of 5.14 years. However, patients who received NACT and had pCR had a 48% better DFS (HR = 0.52), but patients with RD had significantly worse DFS (HR = 2.36) compared with patients who had received ACT. 

The authors determined that in TNBC, OS, but not DFS, of ACT exceeded that of NACT. They further concluded that if RD was present following NACT, both OS and DFS decreased compared with ACT. However, if a pCR was present following NACT, both OS and DFS improved compared with ACT. A caveat is that there may have been selection bias since patients with more severe disease tended to receive NACT. The investigators also suggested that the poorer response to NACT may be due to the biology of the disease as well as to a delay effect since ACT is associated with earlier tumor debulking reducing the opportunity for systemic tumor seeding and metastases. 

This meta-analysis has several limitations, including heterogeneity among studies and failure to distinguish disease stage. Other methodological issues were that HR and confidence intervals were extracted from survival curves as opposed to utilizing those in the published studies, and that the majority of the trials included in the meta-analysis were retrospective.

In spite of these shortcomings, this study provides guidance for pharmacists involved in the management of patients with TNBC.

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