Value of estrogenic recruitment before chemotherapy: first randomized trial in primary breast cancer.
OBJECTIVE
Several preclinical studies showed that short-term pretreatment of breast cancer cells with estrogens can increase the antitumor efficacy of different cytotoxic drugs. Some early clinical studies in patients with advanced breast cancer did seem to support these findings. Therefore, the efficacy of estrogenic recruitment followed by chemotherapy was compared with that of chemotherapy alone in a randomized phase III study in women with lymph node-positive primary breast cancer.


METHODS
Three hundred twenty-eight patients with stage II/IIIA breast cancer who were younger than 66 years of age were randomly allocated to chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) or FAC plus pretreatment with ethinyl estradiol (EE(2)). FAC (500, 50, and 500 mg/m(2), respectively) was administered intravenously once every 4 weeks for four cycles. EE(2) (0.5 mg) was administered orally, both 24 hours and immediately preceding FAC chemotherapy.


RESULTS
Patient and tumor characteristics and chemotherapy dosages were comparable in both treatment groups. Of 318 assessable patients, with a median follow-up of 6.8 years, 177 patients had a relapse and 127 died. No significant differences were observed between the two treatment groups with respect to relapse-free, local recurrence-free, and overall survival according to univariate and multivariate analyses adjusted for age, menopausal status, tumor size, grade, number of positive nodes, and steroid-receptor status. The power for the detection of an increase of 50% in the median relapse-free survival was 80%.


CONCLUSIONS
Estrogenic recruitment of breast cancer cells before FAC chemotherapy did not influence the efficacy of adjuvant chemotherapy in stage II/IIIA breast cancer patients after a follow-up of 6.8 years.
Bontenbal
M
M
Departments of Medical Oncology, Statistics, Surgery, and Radiotherapy, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), University Hospital Rotterdam, Rotterdam, The Netherlands. bom@onch.azr.nl
van Putten
W L
WL
Burghouts
J T
JT
Baggen
M G
MG
Ras
G J
GJ
Stiegelis
W F
WF
Beudeker
M
M
Janssen
J T
JT
Braun
J J
JJ
van der Linden
G H
GH
van der Velden
P C
PC
van Geel
A N
AN
Helle
P
P
Leisink
M
M
Foekens
J A
JA
Klijn
J G
JG
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D012074:Remission Induction; D015996:Survival Rate
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D004997:Ethinyl Estradiol; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil