Doublecortin-Like Kinase 1 Expression in HER2-Positive Breast Cancer: Relation to Clinicopathological Characteristics and Response to Subcutaneous Injection of Pertuzumab-Trastuzumab (Phesgo) as a Part of Neoadjuvant Chemotherapy.

Neoadjuvant therapy is backbone strategy for breast cancer (BC). Neoadjuvant subcutaneous administration of combined Pertuzumab and Trastuzumab (Phesgo) was approved in HER2-positive BC. Pathologic complete response (pCR) to neoadjuvant therapy indicates favorable patients' prognosis. Doublecortin-like kinase 1 (DCLK1) could promote chemoresistance. Little is known about the relation of DCLK1 to neoadjuvant therapy response in HER2-positive BC. Assessment of pCR, toxicity profile to Phesgo subcutaneous administration, and DCLK1 immunohistochemical expression in 104 cases of HER2-positive BC were done. Kaplan-Meier curves were used to estimate overall survival (OS) and progression free survival (PFS) in relation to pCR and DCLK1 expression. High DCLK1 expression (46.2%) was associated with large tumor size, grade III tumors, lymph node metastasis, high Ki-67 index, and poor neoadjuvant therapy response. pCR (62.5%) was related to older age, negative lymph node status, and low DCLK1 expression. Phesgo was tolerable and didn't cause cardiac toxicity or anaphylaxis. OS and PFS were higher in patients showed pCR and low DCLK1 expression. Dual blockade of HER2 using Phesgo is associated with pCR and better OS/PFS without adding more toxicity. High DCLK1 expression is related to unfavorable clinicopathologic parameters and poor response to neoadjuvant therapy, together with shorter OS/PFS.