title: Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study.
abstract: Treatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics.
  
  
  
  The population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985-2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models.
  
  
  
  Compared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55-0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53-1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1-4 years (RR = 0.59; 95 % CI = 0.45-0.77) and 5-9 years (RR = 0.73; 95 % CI = 0.56-0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies.
  
  
  
  Our findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed.
authors.affiliation: Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Langballe
authors.affiliation: Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark. lene@cancer.dk.
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjær
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.affiliation: University of Iowa, Iowa City, IA, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA, USA.|Department of Health Research and Policy (Epidemiology) and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.|University of Toronto, Dalla Lana School of Public Health, Toronto, Canada.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.affiliation: Beckman Research Institute of the City of Hope, Duarte, CA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.affiliation: University of Toronto, Dalla Lana School of Public Health, Toronto, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Brooks
authors.affiliation: Department of Oncology at Rigshospitalet, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Andersson
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Woods
authors.affiliation: University of Florida Genetics Institute, Gainesville, FL, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Concannon
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D016017:Odds Ratio; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: Breast cancer; Chemotherapy; Contralateral breast cancer; Tamoxifen