Fifteen-year median follow-up results after neoadjuvant doxorubicin, followed by mastectomy, followed by adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) followed by radiation for stage III breast cancer: a phase II trial (CALGB 8944)

Abstract

Purpose-To describe long-term results of a multimodality strategy for stage III breast cancer utilizing neoadjuvant doxorubicin followed by mastectomy, CMF, and radiotherapy.Patients and methods-Women with biopsy-proven, clinical stage III breast cancer and adequate organ function were eligible. Neoadjuvant doxorubicin (30 mg/m 2 days 1-3, every 28 days for 4 cycles) was followed by mastectomy, in stable or responding patients. Sixteen weeks of postoperative CMF followed (continuous oral cyclophosphamide (2 mg/kg/day); methotrexate (0.7 mg/kg IV) and fluorouracil (12 mg/kg IV) weekly, weeks 1-8, and than biweekly, weeks 9-16). Radiation therapy followed adjuvant chemotherapy.Results-Clinical response rate was 71% (79/111, 95% CI = 62-79%), with 19% complete clinical response. Pathologic complete response was 5% (95% CI = 2-11%). Median follow-up is 15.6 years. Half of the patients progressed by 2.2 years; half died by 5.4 years (range 6 months-15 years). The hazard of dying was greatest in the first 5 years after diagnosis and declined thereafter. Time to progression and overall survival were predicted by number of pathologically involved lymph nodes (TTP: HR [10 vs. 1 node] 2.40, 95% CI = 1.63-3.53, P < 0.0001; OS: HR 2.50, 95% CI = 1.74-3.58, P < 0.0001).Conclusions-After multimodality treatment for locally advanced breast cancer, long-term survival was correlated with the number of pathologically positive lymph nodes, but not to clinical response. The hazard of death was highest during the first 5 years after diagnosis and declined thereafter, indicating a possible intermediate endpoint for future trials of neoadjuvant treatment.

Long-Term Outcomes in Stage IIIB Breast Cancer Patients Who Achieved Less Than a Pathological Complete Response (&lt;pCR) After Primary Chemotherapy

“…The median times from the start of primary chemotherapy to first recurrence and death were 17 months (range, 6 -122 months) and 40 months (range, 12-127 months), respectively. These results are consistent with other studies [12,26,27]. Patients with residual disease in the axilla with or without residual disease in the breast had lower DFS and OS rates than patients with residual disease in the breast only.…”

“…Most recurrences occur within 3-5 years of initial treatment, with an early peak of recurrence around 12-18 months following surgery [11,12]. Recurrence synchronization has been shown to occur after surgery when it is followed by chemotherapy [11] or when surgery follows chemotherapy in the neoadjuvant setting [26]. Currently, after optimal multimodal treatment, no further standard therapy exists for patients who fail to achieve a pCR.…”

A Molecular Analysis Provides Novel Insights into Androgen Receptor Signalling in Breast Cancer

“…In order to observe the effects of DHT on cell apoptosis, we selected three well known drugs namely paclitaxel, cyclophosphamide and 5-fluorouracil used in chemotherapy of breast cancer. Cyclophosphamide and 5-fluorouracil along with methotrexate are commonly used as CMF (cyclophosphamide, methotrexate and 5-fluorouracil) adjuvant and neoadjuvant chemotherapy for the treatment of breast cancer [ 56 , 57 ]. Paclitaxel (taxol) is a member of the taxane class of agents, that targets microtubules and induces apoptosis and it is currently used for the treatment of a wide range of carcinomas including breast, ovarian and non-small cell lung cancers [ 58 ].…”

Guía de práctica clínica para el manejo del cáncer de mama en estadios tempranos, localmente avanzados y metastásicos

“…El pronóstico de los pacientes que no logran una pCR con QT neoadyuvante es peor comparado con quienes sí lo hacen, especialmente en pacientes con triple negativo o HER2+ tipos. Sin embargo, se desconoce si el uso de QT adyuvante en pacientes que ya han recibido tratamiento neoadyuvante completo es suficiente como para justificar su toxicidad 85,86 .…”