Efficacy and safety of concurrent trastuzumab plus weekly paclitaxel–FEC as primary therapy for HER2-positive breast cancer in everyday clinical practice

• Published in: Breast cancer research and treatment Vol. 134; no. 3; pp. 1161 - 1168
• Main Authors: Pernas, Sonia, Gil-Gil, Miguel, de Olza, María Ochoa, Gumà, Anna, Climent, Fina, Petit, Anna, Pla, María Jesús, García-Tejedor, Amparo, López-Ojeda, Ana, Falo, Cati, Fernandez-Otega, Adela, Mesia, Carlos, Pérez-Martin, Francisco Javier, Urruticoechea, Ander, Germà, Josep Ramon
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-08-2012; Springer; Springer Nature B.V
• Subjects: Anthracyclines; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Cancer research; Cancer therapies; Cardiac patients; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant; Clinical Trial; Cyclophosphamide - administration & dosage; Effectiveness; Epidermal growth factor; Epirubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Monoclonal antibodies; Neoplasm Staging; Oncology; Paclitaxel - administration & dosage; Patient safety; Receptor, ErbB-2 - metabolism; Trastuzumab; Treatment Outcome; Tumors; Pathological complete response; Anthracyclines; HER2-positive breast cancer; Primary therapy; Trastuzumab; Cardiac toxicity; Antineoplastic agent; Heart; Breast disease; Toxicity; Concurrent; erbB2 Gene; Administration schedule; Monoclonal antibody; Taxane derivatives; Paclitaxel; Primary; Safety; Antimitotic; Protooncogene; Treatment efficiency; Breast cancer; Malignant tumor; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Treatment; C-Onc gene; Anthracyclins; Circulatory system; Cancer
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-012-2149-7

One of the most efficacious primary therapies in HER2-positive breast cancer was published by the M.D. Anderson group in 2005. This randomized trial evaluated the addition of trastuzumab to a taxane–anthracycline based chemotherapy. Despite largely significant differences in pathological complete response (pCR) in the trastuzumab group (65 vs. 26 %) this regimen did not become a common standard due to toxicity concerns and its premature closure with a small sample size. In order to evaluate the efficacy and safety of this regimen in an off-trial setting we conducted a prospectively monitorized series of consecutive patients with early or locally advanced Her-2 positive breast cancer following the same treatment strategy. Stage II–IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24 weeks administered concurrently with all primary chemotherapy containing paclitaxel (80 mg/m
2
) for 12 weeks and 4 cycles of FEC-75 (fluorouracil 500 mg/m
2
, epirubicine 75 mg/m
2
, and cyclophosphamide 500 mg/m
2
) followed by surgery. The objectives were efficacy, in terms of pCR in both the breast and lymph nodes, and safety, with close cardiac monitoring during and after treatment. From August 2004 to February 2009, 83 patients were included. Most patients (73.5 %) had node involvement and 13.2 % had inflammatory disease. Fifty-one patients (61.4 %) achieved a pCR in breast and axilla (95 % CI 50–72 %). HR-negative tumors were associated with higher pCR rate than HR-positive tumors (77 vs. 48 %,
P
 = 0.006). At a median follow-up of 50.2 months no patient developed symptomatic cardiac failure, and 9 patients (10.8 %) presented a transient asymptomatic decrease in left ventricular ejection fraction. Primary therapy with concurrent trastuzumab plus paclitaxel–FEC for HER2-positive breast cancer in everyday practice is highly effective and safe confirming the results observed in a randomized trial stopped prematurely.