PURPOSE: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer. PATIENTS AND METHODS: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II alpha (TOP2A) and microtubule associated protein tau (MAP-Tau). RESULTS: Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P<0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3-3.9, P=0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER-, 30% for HER2-/ER-, 19% for HER2+/ER+, and 6% for HER2-/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau (P=0.001 and P<0.001) and higher expression of TOP2A mRNAs (P=0.048 and P=0.001) in patients with ER+ disease. ER- cancers had low MAP-tau expression regardless of HER-status. CONCLUSION: HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers.
PURPOSE: We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer. PATIENTS AND METHODS: Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II alpha (TOP2A) and microtubule associated protein tau (MAP-Tau). RESULTS: Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P<0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3-3.9, P=0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER-, 30% for HER2-/ER-, 19% for HER2+/ER+, and 6% for HER2-/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau (P=0.001 and P<0.001) and higher expression of TOP2A mRNAs (P=0.048 and P=0.001) in patients with ER+ disease. ER- cancers had low MAP-tau expression regardless of HER-status. CONCLUSION:HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers.
Authors: Cristina Saura; Ling-Ming Tseng; Stephen Chan; Raju T Chacko; Mario Campone; Alexy Manikhas; Shona M Nag; Cynthia G Leichman; Lokanatha Dasappa; Peter A Fasching; Fernando Hurtado de Mendoza; W Fraser Symmans; David Liu; Pralay Mukhopadhyay; Christine Horak; Guan Xing; Lajos Pusztai Journal: Oncologist Date: 2013-07-12
Authors: I Tusquets; L García-Estévez; E Adrover; L Calvo; I Alvarez; J García Mata; Y Fernández; M Margueli; M A Seguí; M Muñoz; C Rodríguez; A Rodríguez Lescure; R Colomer; P Gascón; M Martín; E Alba; A Barnadas; A Llombart; J Albanell; A Lluch Journal: Clin Transl Oncol Date: 2010-04 Impact factor: 3.405
Authors: Vlad Popovici; Weijie Chen; Brandon G Gallas; Christos Hatzis; Weiwei Shi; Frank W Samuelson; Yuri Nikolsky; Marina Tsyganova; Alex Ishkin; Tatiana Nikolskaya; Kenneth R Hess; Vicente Valero; Daniel Booser; Mauro Delorenzi; Gabriel N Hortobagyi; Leming Shi; W Fraser Symmans; Lajos Pusztai Journal: Breast Cancer Res Date: 2010-01-11 Impact factor: 6.466
Authors: Jae K Lee; Charles Coutant; Young-Chul Kim; Yuan Qi; Dan Theodorescu; W Fraser Symmans; Keith Baggerly; Roman Rouzier; Lajos Pusztai Journal: Clin Cancer Res Date: 2010-01-12 Impact factor: 12.531