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The success of preoperative, neoadjuvant chemotherapy for locally advanced and inflammatory breast cancer, combined with emerging data on the use of adjuvant chemotherapy, led to the evaluation of the primary systemic therapy (PST) (neoadjuvant) approach for women with primary operable breast cancer. Potential advantages of PST include increasing rates of breast conservation, reducing mortality with lower toxicity, and in vivo testing of sensitivity of cancer cells to the systemic therapy used.1
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Both the German Breast Group (GBG), an academic research organization conducting clinical trials on breast cancer therapy, as well as the German Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie [AGO]) in the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe [DGGG]) and the German Cancer Society (Deutsche Krebsgesellschaft) have performed a comprehensive randomized clinical trial program evaluating the role of neoadjuvant chemotherapy for women with primary breast cancer.
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GeparDo Study Program
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After a dose-finding phase IIa study,2 the first randomized study (GeparDo) of the GBG series of neoadjuvant trials investigated the effect of adding tamoxifen to a preoperative dose-dense doxorubicin and docetaxel regimen on the pathologic response in 250 women with primary operable breast cancer (tumor size ≥3 cm, N0–2, M0).3 Patients were prospectively randomized to receive every 14 days a total of 4 cycles of doxorubicin, 50 mg/m2, and docetaxel, 75 mg/m2 (ADoc), with or without tamoxifen. Granulocyte colony-stimulating factor (G-CSF) was routinely given on days 5 to 10. Surgery followed 8 to 10 weeks after the start of treatment. The results showed that a dose-dense regimen of ADoc with G-CSF offers high compliance, moderate toxicity, and can achieve a pathologic complete response (pCR) rate of 9.7%; however, tamoxifen did not increase antitumor activity. A further 2.4% of patients showed only nonresidual disease in the surgically removed tissue.
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The phase III GeparDuo study randomized 913 patients with untreated operable breast cancer (T2–3, N0–2, M0) to 2 neoadjuvant chemotherapy regimens. The primary end point of the study was to compare the pCR rate in the breast and axillary nodes with the 8-week dose-dense combination regimen ADOC (doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, every 14 days for 4 cycles with filgrastim support), as studied in GeparDo, with that of a 24-week sequential schedule of AC followed by docetaxel (AC-DOC; doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, every 21 days followed by docetaxel, 100 mg/m2, every 21 days for 4 cycles each). All patients received tamoxifen simultaneously to chemotherapy irrespective of the hormone receptor content of the tumors.4
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A pCR was achieved in 94 patients (10.6%), but the likelihood was significantly greater with AC-DOC (14.3%; n = 63) than with the ADOC regimen (7.0%; n = 31) (odds ratio, 2.22; 90% confidence interval [CI], 1.52 ...