A Phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma

Abstract

BACKGROUNDThe current study was performed to assess whether sequential potentially noncross‐resistant chemotherapy prolongs disease‐free survival (DFS) and overall survival (OS) in patients with operable breast carcinoma.METHODSSeven hundred eighty‐nine patients were registered and followed for a median of 10 years. They were treated in two groups. In Group 1, patients age < 50 years or age > 50 years but with either negative or unknown estrogen receptor (ER) status were randomized to receive 6 cycles of 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC) alone or followed by 4 cycles of methotrexate and vinblastine (MV). In Group 2, patients age ≥ 50 years with ER‐positive disease were randomized to receive either tamoxifen or combination chemotherapy (FAC + MV) for 10 cycles. Analysis was performed according to allocated treatment (intention to treat), with all randomized patients included.RESULTSIn Group 1 there were no significant differences with regard to DFS or OS between the two treatment arms. The DFS at 5 years was 0.70 and 0.76, respectively, for FAC compared with FAC+MV (P = 0.26). The OS was similar for both groups (0.84 vs. 0.83). It is interesting to note that there was a statistically nonsignificant trend for improved DFS in the FAC + MV arm for patients who were ER‐positive. In Group 2, tamoxifen alone led to more prolonged DFS compared to FAC+MV (0.78 vs. 0.66, respectively) but this did not reach statistical significance (P = 0.28). OS also was associated with a trend (P = 0.86) toward prolonged survival for the tamoxifen arm compared with the FAC+MV arm (0.85 vs. 0.74, respectively).CONCLUSIONSThe results of the current trial concerning sequential adjuvant chemotherapy for operable breast carcinoma, which to our knowledge contains the longest follow‐up presented to date, failed to demonstrate any additional benefit from the addition of 4 cycles of MV to 6 cycles of FAC chemotherapy. Cancer 2003;97:2716–23. © 2003 American Cancer Society.DOI 10.1002/cncr.11396

Coexpression of α6β4 Integrin and Guanine Nucleotide Exchange Factor Net1 Identifies Node-Positive Breast Cancer Patients at High Risk for Distant Metastasis

“…Although patients ≥50 y of age with estrogen receptor–positive disease were randomized to receive tamoxifen or 6 cycles of fluorouracil, doxorubicin, and cyclophosphamide plus 4 cycles of methotrexate and vinblastine, those who received tamoxifen were excluded from our retrospective study, so all patients in our study received doxorubicin-based chemotherapy without tamoxifen. The previous clinical protocol failed to show any benefit from the addition of four cycles of methotrexate and vinblastine to six cycles of fluorouracil, doxorubicin, and cyclophosphamide, so both groups were regarded as having similar doxorubicin-based chemotherapy (26). …”

Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma

“…In Group 2, patients Ն 50 years with ER-positive disease were randomized to receive either tamoxifen or combination chemotherapy (FAC and MV) for 10 cycles. 24 The 96 patients selected for immunohistochemistry study were the only patients treated with FAC from whom tissue specimens were available. All patients underwent mastectomy or breast-conserving surgery between December 1986 and January 1994.…”

Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

“…Considering that the next line of chemotherapy against TAM-resistant breast cancer involves a methotrexate-or cisplatin-containing regimen (Blumenschein et al 1997, Assikis et al 2003, a study on whether the expression levels of the ABC transporter can be changed in TAM-resistant breast cancer cells might lead to a better understanding of the pathological implications of TAM resistance. This study shows for the first time that the expression of MRP2 is higher in TAMR-MCF-7 cells when compared with those in MCF-7 cells and demonstrates that the phosphatidylinositol 3-kinase (PI3-kinase)-dependent activation of PXR is essential for the induction of MRP2 in TAM-resistant breast cancer cells.…”