Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the Women's Environment, Cancer and Radiation Epidemiology Study.
BACKGROUND
Results from randomized trials indicate that treatment with tamoxifen or chemotherapy for primary breast cancer reduces the risk for contralateral breast cancer. However, less is known about how long the risk is reduced and the impact of factors such as age and menopausal status.


METHODS
The study included 634 women with contralateral breast cancer (case patients) and 1158 women with unilateral breast cancer (control subjects) from the Women's Environment, Cancer and Radiation Epidemiology Study. The women were younger than age 55 when they were first diagnosed with breast cancer during 1985-1999. Rate ratios (RRs) and 95% confidence intervals (CIs) for contralateral breast cancer after treatment with chemotherapy or tamoxifen were assessed by multivariable adjusted conditional logistic regression analyses.


RESULTS
Chemotherapy was associated with a lower risk for contralateral breast cancer (RR = 0.57, 95% CI = 0.42 to 0.75) than no chemotherapy. A statistically significant association between chemotherapy and reduced risk for contralateral breast cancer persisted up to 10 years after the first breast cancer diagnosis and was stronger among women who became postmenopausal within 1 year of the first breast cancer diagnosis (RR = 0.28, 95% CI = 0.11 to 0.76). Tamoxifen use was also associated with reduced risk for contralateral breast cancer (RR = 0.66, 95% CI = 0.50 to 0.88) compared with no use, and the association was statistically significant for 5 years after the first diagnosis.


CONCLUSIONS
The associations between chemotherapy and tamoxifen treatment and reduced risk for contralateral breast cancer appear to continue for 10 and 5 years, respectively, after the initial breast cancer is diagnosed. Ovarian suppression may have a role in the association between chemotherapy and reduced risk for contralateral breast cancer.
Bertelsen
Lisbeth
L
Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark. lisbethb@cancer.dk
Bernstein
Leslie
L
Olsen
Jørgen H
JH
Mellemkjaer
Lene
L
Haile
Robert W
RW
Lynch
Charles F
CF
Malone
Kathleen E
KE
Anton-Culver
Hoda
H
Christensen
Jane
J
Langholz
Bryan
B
Thomas
Duncan C
DC
Begg
Colin B
CB
Capanu
Marinela
M
Ejlertsen
Bent
B
Stovall
Marilyn
M
Boice
John D
JD
Shore
Roy E
RE
Bernstein
Jonine L
JL
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000517:prevention & control / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D015986:Confounding Factors, Epidemiologic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008593:Menopause / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D015999:Multivariate Analysis; D016609:Neoplasms, Second Primary / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects*; D018714:Radiotherapy, Adjuvant; D012107:Research Design; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate