Clinicopathologic Predictors of Pathologic Complete Response after Neoadjuvant Systemic Therapy and Impact on Surgical Management

Abstract

Neoadjuvant systemic therapy previously given for inoperable breast cancer is increasingly being administered in early breast cancer especially in triple negative and HER2 positive molecular subtypes. It is associated with an increased rate of complete pathologic response (PCR) which is a surrogate marker for good survival outcomes and has role in de escalation of surgical management.  We conduct this study to identify clinical and pathologic factors and systemic treatment regimens that predict PCR among Pakistan’s breast cancer patients and its impact on surgical management. Materials and Methods: Patients with clinical stage I-III who received Neoadjuvant systemic therapy (NST) and underwent surgical intervention at Liaquat national hospital were included. The clinicopathologic factors included age, menopausal status, clinical tumor size, nodal status, stage, pathologic type, grade, molecular subtype, PR status, pathologic response, and treatment in terms of systemic therapy. The surgery underwent and pathologic stage(ypTN) were recorded. The association between these factors and PCR was analyzed with the chi-square test. Univariate analysis was performed to evaluate the influence of clinicopathologic factors on PCR. Results: PCR was achieved in 174(19.6%) out of the 889 patients. There was a significant association (P-value <0.001) with molecular subtype as follows PCR percentage for HER 2 enriched-39% and luminal B HER 2 positive-31%, triple negative-25% ,Luminal A-6.5% and Luminal B-9.6%, progesterone receptors negative tumors (PCR-26.9%) and chemotherapy regime-Anthracycline and taxane PCR-28%. The predictive value of the three factors remains significant on univariate analysis. The breast conservative surgery rate was 34%, sentinel node biopsy was 60% and axillary PCR is seen in 20% of the patients (cN+ 60% to ypN+ 40%). Conclusion: NST has a good overall impact in terms of achieving PCR and downsizing for breast-conserving surgery with better cosmetic outcome and de-escalation of axillary surgery. The positive predictive factors include molecular subtype, Her2 positive tumors being the most sensitive, progesterone receptor-negative tumors, and anthracycline and taxane-based chemotherapy.