A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada--Clinical Trials Group Trial, MA.12).
BACKGROUND
In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear.


METHODS
Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy.


RESULTS
Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices.


CONCLUSIONS
Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.
Bramwell
V H C
VHC
Department of Medical Oncology, Tom Baker Cancer Centre, Calgary, Alberta. Electronic address: vivienbr@cancerboard.ab.ca.
Pritchard
K I
KI
Department of Medical Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario.
Tu
D
D
Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
Tonkin
K
K
Department of Medical Oncology, Cross Cancer Institute, Edmonton, Alberta.
Vachhrajani
H
H
Department of Radiation Oncology, Saskatoon Cancer Centre, Saskatoon, Saskatchewan.
Vandenberg
T A
TA
Department of Medical Oncology, London Regional Cancer Program, London, Ontario.
Robert
J
J
Department of Surgical Oncology, Hôpital Du Saint-Sacrement, Quebec City, Quebec.
Arnold
A
A
Department of Medical Oncology, Juravinski Cancer Centre, Hamilton, Ontario.
O'Reilly
S E
SE
Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Graham
B
B
Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
Shepherd
L
L
Central Office, National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario.
D000047:Academies and Institutes; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002170:Canada; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D010919:Placebos; D017697:Premenopause / Q000187:drug effects; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*; D013997:Time Factors
D000970:Antineoplastic Agents; D010919:Placebos; D013629:Tamoxifen