PO-HAN LINTseng, Ling-MingLing-MingTsengLee, Yi-HsuanYi-HsuanLeeChen, Shou-TungShou-TungChenYeh, Dah-CherngDah-CherngYehDai, Ming-ShenMing-ShenDaiLiu, Liang-ChihLiang-ChihLiuMING-YANG WANGCHIAO LOChang, StanleyStanleyChangTan, Kien ThiamKien ThiamTanChen, Shu-JenShu-JenChenSUNG-HSIN KUOCHIUN-SHENG HUANG2022-07-292022-07-292022-120929-6646https://www.scopus.com/inward/record.uri?eid=2-s2.0-85132855311&doi=10.1016%2fj.jfma.2022.05.015&partnerID=40&md5=253db916f6800ae8b04b4e88c754684dhttps://scholars.lib.ntu.edu.tw/handle/123456789/616051Background: The 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. Methods: Patients 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. Results: Twenty-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). Conclusion: Adding 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.enafatinibHomologous recombinationNeoadjuvantPI3KTriple-negative breast cancer[SDGs]SDG3journal article10.1016/j.jfma.2022.05.015357525292-s2.0-85132855311