Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer?

• FDA uses pCR as an endpoint to support new drug accelerated approval for high-risk early breast cancer.
• Different pCR definitions exist in the literature.
• FDA recommands yPT0/Tis yPN0 as a pCR definition.
• pCR rates varies among the different BC subgroups: higher in luminal B, HER2+ and TNBC.
• pCR is predictive for DFS and OS in HER2+ and TNBC and even not clear in luminal BC.

Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the “in vivo” efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).