• Po-Han Lin, Ling-Ming Tseng, Yi-Hsuan Lee, Shou-Tung Chen, Dah-Cherng Yeh, Ming-Shen Dai, Liang-Chih Liu, Ming-Yang Wang, Chiao Lo, Stanley Chang, Kien Thiam Tan, Shu-Jen Chen, Sung-Hsin Kuo, and Chiun-Sheng Huang.
• Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
• J Formos Med Assoc. 2022 Dec 1; 121 (12): 253825472538-2547.

BackgroundThe prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting.MethodsPatients with stage II to III TNBC were enrolled. They received 40 mg of afatinib daily for 14 days, followed by daily afatinib and weekly paclitaxel (80 mg/m2) every 21 days for four to six cycles. To explore the mechanisms of responsiveness and non-responsiveness, 409 cancer-associated genes were sequenced.ResultsTwenty-one patients were enrolled and one patient achieved a complete clinical response; however, a 2 mm residual tumor was noted in the surgical specimen. Overall, 33.0% patients were responders. Fifteen patients received molecular testing. No activated mutation of EGFR or Her2 were found. Activated PI3K or JAK2 pathway were trended to associate with non-responder (p = 0.057). Mutation of homologous recombination (HR) genes were correlated with non-responsiveness (p = 0.005). Seven patients did not have altered PI3K, JAK2 or HR pathway; six (85.7%) of them were responder. Patients with the amplified DAXX gene was associated with a favorable trend of response (p = 0.109).ConclusionAdding afatinib to neoadjuvant paclitaxel generated a modest effect in TNBC. Exploratory molecular analysis suggested that activated PI3K, JAK2 pathways and mutation of HR genes were associated with therapeutic non-responsiveness, and amplification of DAXX genes was associated with responsiveness to afatinib in combination with paclitaxel.Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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