BACKGROUND: Four major clinical trials have established that trastuzumab added to adjuvant systemic chemotherapy for women with HER2+ breast cancer significantly improves disease-free and overall survival compared with chemotherapy alone. We evaluated pathologic complete response (pCR) rate and cardiac safety of preoperative doxorubicin and cyclophosphamide followed by a taxane with or without trastuzumab. PATIENTS AND METHODS: We reviewed pCR rate and change in left ventricular ejection fraction in women with operable HER2+ breast cancer (defined as immunohistochemical 3+ or fluorescence in situ hybridization ratio > or = 2.2) who were treated between 2002 and 2008 with doxorubicin and cyclophosphamide followed by a taxane with or without trastuzumab before definitive breast surgery. RESULTS: We identified 33 patients, of whom 42.4% received preoperative chemotherapy without trastuzumab and 57.6% of whom received trastuzumab with chemotherapy. The pCR rates were 28.6% and 52.6% in the group that received chemotherapy alone or with trastuzumab, respectively (odds ratio, 2.78; 95% CI, 0.64-12.1; P = .173). Severe cardiac events or treatment delays as a result of cardiac toxicity were not observed. With a median follow-up time of 14 months, 21.4% of patients in the non-trastuzumab group and 10.5% in the trastuzumab group had disease recurrence. CONCLUSION: Sequential administration of preoperative doxorubicin and cyclophosphamide followed by a taxane and trastuzumab combination is safe in women with primary operable HER2+ breast cancer and is associated with a high pCR rate. Large randomized phase III clinical trials are evaluating the role of preoperative trastuzumab when added to anthracycline- and/or taxane-based regimens.
BACKGROUND: Four major clinical trials have established that trastuzumab added to adjuvant systemic chemotherapy for women with HER2+ breast cancer significantly improves disease-free and overall survival compared with chemotherapy alone. We evaluated pathologic complete response (pCR) rate and cardiac safety of preoperative doxorubicin and cyclophosphamide followed by a taxane with or without trastuzumab. PATIENTS AND METHODS: We reviewed pCR rate and change in left ventricular ejection fraction in women with operable HER2+ breast cancer (defined as immunohistochemical 3+ or fluorescence in situ hybridization ratio > or = 2.2) who were treated between 2002 and 2008 with doxorubicin and cyclophosphamide followed by a taxane with or without trastuzumab before definitive breast surgery. RESULTS: We identified 33 patients, of whom 42.4% received preoperative chemotherapy without trastuzumab and 57.6% of whom received trastuzumab with chemotherapy. The pCR rates were 28.6% and 52.6% in the group that received chemotherapy alone or with trastuzumab, respectively (odds ratio, 2.78; 95% CI, 0.64-12.1; P = .173). Severe cardiac events or treatment delays as a result of cardiac toxicity were not observed. With a median follow-up time of 14 months, 21.4% of patients in the non-trastuzumab group and 10.5% in the trastuzumab group had disease recurrence. CONCLUSION: Sequential administration of preoperative doxorubicin and cyclophosphamide followed by a taxane and trastuzumab combination is safe in women with primary operable HER2+ breast cancer and is associated with a high pCR rate. Large randomized phase III clinical trials are evaluating the role of preoperative trastuzumab when added to anthracycline- and/or taxane-based regimens.
Authors: Soley Bayraktar; Ana M Gonzalez-Angulo; Xiudong Lei; Aman U Buzdar; Vicente Valero; Amal Melhem-Bertrandt; Henry M Kuerer; Gabriel N Hortobagyi; Aysegul A Sahin; Funda Meric-Bernstam Journal: Cancer Date: 2011-09-27 Impact factor: 6.860