NSABP B-38

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recently, oncologists have begun treating breast cancer patients with dose dense (DD) regimens. This means that the patients receive the chemotherapy drugs over a much shorter period of time. Surprisingly, the overall toxicities experienced by the patients is no worse and the efficacy equal if not superior. Studies have shown that women with breast cancer treated with Docetaexel/Doxorubicin/Cyclophosphamide (TAC) (Arm I) or ddose-dense. Doxorubicin/Cyclophosphamide followed by DD Paclitaxel (DD AC-P) (Arm II) have improved treatment outcome compared to previously used chemotherapy regimens. Unfortunately some women still develop local, regional, and systemic disease recurrence. This reality provides a compelling reason to continue efforts to further improve therapy for node-positive breast cancer. To date there has not been a study to directly compare TAC to DD AC-P and this trial will provide that cornparison. Another potential advantage of DD AC-P is that it's reported toxicity profile provides opportunity for incorporating a fourth chemotherapy agent into the program. The anti-metabolite gemcitabine has shown promise in combination with paclitaxel for treatment of mestastatic breast cancer arguing for its potential use in the adjuvant setting. A phase 2 study of gemcitabine in combination with paclitaxel as a third-line therapy showed a response rate of 55% with a manageable toxicity profile. On the basis of the activity of the gemcitabine/paclitaxel combination demonstrated in these trials, coupled with the favorable toxicity profile of the dose-dense schedule, they propose to determine whether sequential dose-dense AC followed by DD AC-PG (Arm III) can further imrove the outcome provided by both TAC and DD AC-P. The primary aims of this study are to determine whether the DD AC-PG regimen is superior to the TAC and the DD AC-P regimens in improving DFS and to compare the relative DFS of TAC and DD AC-P. Secondary aims are to determine whether DD AC-PG is superior to TAC and DD AC-P in improving overall survival, compare survival of the TAC and DD AC-P regimens Alone, and to compare the toxicities of the 3 regimens. Study Design: The study will be conducted in women with operable, invasive carcinoma of the breast with histologically positive axillary nodes. Patients will be stratified by number of positive nodes, hormone receptor status, and type of surgery and planned radiotherapy. Followwing stratification, patients wi11 be randomized to 1 of the 3 chemotherapy regimens. Women with ER positive and/or PR positive tumors should receive hormonal therapy for a minimum of 5 years following completion of chemotherapy. All women who have had a lumpectomy wi11 have whole breast irradiation. Chest wall and regional nodal irradiation will be prospectively determined at the discretion of the investigator and will be used as a stratification factor. The study will enroll 4800 patients.