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Introduction
Background and rationale {6a}
Triple-negative breast cancer (TNBC) accounts for 12–13% of all breast cancers in the Western population [1]. The prevalence of TNBC varies considerably globally, with it being more frequent in young women and in African-American women compared to white women [2] The risk of TNBC is more is 2.7 times higher in black women compared to whites [3]. It is the most aggressive subtype of breast cancer, associated with poorer outcomes when compared with other subtypes, even when adjusted for stage and other prognostic factors [3]. The prevalence of TNBC is lower in the Asian population; however, in India, the proportion of patients with TNBC has been reported to be as high as 31% [4, 5], likely due to the younger average population in India. There is a higher prevalence in premenopausal women, and patients with TNBC are more likely to present with larger tumor size and metastatic disease as compared with other subtypes [6]. The maximum chance of cure for patients with TNBC is at an early stage, and once metastatic, the prognosis remains poor, with a median overall survival of approximately 15 months [7]. Even at an earlier stage, the risk of metastatic recurrence is higher compared to other subtypes of breast cancer [8].
The management of early TNBC has witnessed a paradigm shift to neoadjuvant chemotherapy in the early stage [9]. This approach provides an opportunity to assess the in vivo pathological response to neoadjuvant chemotherapy. In patients where a pathological complete response is observed, the prognosis is significantly better than that of those with residual disease [10]. Additional systemic treatment with capecitabine for 6 months in patients with residual disease showed significant improvement in overall survival [11]. Furthermore, adding pembrolizumab, an immune checkpoint inhibitor, also improved the pathological complete response and disease-free survival in these patients.
In the Keynote 522 trial, patients with stage I-III TNBC were randomized in a 2:1 ratio to receive pembrolizumab or placebo in addition to 8 cycles of neoadjuvant chemotherapy (4 cycles of carboplatin and paclitaxel followed by 4 cycles of epirubicin/docetaxel and cyclophosphamide). These patients then underwent surgery, followed by pembrolizumab or placebo every 3 weeks for up to nine cycles. This trial demonstrated increased pathological complete response and event-free survival...