Bernatsky, et al: Breast cancer in lupus 1505 From the Division of Clinical Epidemiology, Division of Clinical Immunology/Allergy, and Department of Oncology, Montreal General Hospital; and the Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada; and the Division of Rheumatology, Northwestern University, Chicago, Illinois, USA. Supported by The Arthritis Society, The Canadian Arthritis Network, The Canadian Institute of Health Research (CIHR), The National Cancer Institute of Canada, Lupus Canada, and The Singer Family Fund for Lupus Research. Dr. Ramsey-Goldman is supported by an Arthritis Foundation Clinical Science Grant, and National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institute of Health grants. S. Bernatsky, MD, MSc, FRCPC; R. Ramsey-Goldman, MD, Dr PH; J.F. Boivin, MD, ScD, FRCPC; L. Joseph, PhD, Senior CIHR Investigator; A.D. Moore, MD, FRCPC; R. Rajan, MD, MSc, FRCPC, FRSQ, Clinician Scholar; A. Clarke, MD, MSc, FRCPC, CIHR Investigator. Address reprint requests to Dr. S. Bernatsky, 1650 Cedar Ave., Room L10-520, Montreal, Quebec, H3G 1A4. Submitted September 4, 2002; revision accepted December 16, 2002. Evidence of the association between systemic lupus erythe- matosus (SLE) and malignancy has accumulated over the past several years 1-4 . Breast cancer has been reported to be of increased incidence in several SLE cohort studies 5,6 and in a metaanalysis 7 . Of the studies done to date, few 5,8 have explored how the prevalence of factors traditionally associ- ated with malignancy may be influencing cancer risk in SLE, and none have adequately examined factors specifi- cally related to breast cancer. This is disconcerting, since some important breast cancer risk factors, such as nulli- parity, appear to be increased in SLE 9 . Our objective was to estimate the extent to which the rate of breast cancer in a combined SLE cohort would resemble that of the general population, after adjusting for the cohort members’ risk factor profiles. MATERIALS AND METHODS Patients. Data were pooled from the SLE clinic cohorts of 2 centers, the Montreal General Hospital and the Feinberg School of Medicine at Northwestern University in Chicago. Consecutive patients with American College of Rheumatology criteria 10,11 for SLE were enrolled in these clinic cohorts at the time they presented for their first clinic visit. There were 613 patients in the combined cohort, including 583 women. Institutional review board approval was obtained at the respective sites. Analysis. The Gail model is an established model for predicting breast cancer risk 12 that includes age, early menarche, breast cancer in a first degree relative, nulliparity, late age at first childbirth, and history of benign breast disease as predictors. For each subject, this model was used to esti- mate the probability that breast cancer would develop during the observa- tion interval. The actual occurrence of breast cancer cases was determined by linkage with regional cancer registries. Data required by the Gail model were obtained from a survey of risk factors that had been administered at the time of the cancer registry linkage (1995 in Chicago and 1998 in Montreal). For those patients who had died or been lost to followup (approximately one-third of the sample), data were abstracted from the database or medical records. This was also done for 23 living patients who consented to participate but who did not wish to complete a questionnaire. A conservative approach was taken to missing data on subjects’risk factors, by replacing missing values with the higher risk category. This maximizes the expected number of cancers and thus prevents overestimation of the observed to expected ratio. After estimating the probability of developing breast cancer during the observation interval for each patient, the probabilities were summed to Do Traditional Gail Model Risk Factors Account for Increased Breast Cancer in Women with Lupus? SASHA BERNATSKY, ROSALIND RAMSEY-GOLDMAN, JEAN-FRANÇOIS BOIVIN, LAWRENCE JOSEPH, ANDREW D. MOORE, RAGHU RAJAN, and ANN CLARKE ABSTRACT. Objective. To determine to what extent the observed experience of breast cancer in a combined cohort of patients with systemic lupus erythematosus (SLE) could be explained by the profile of breast cancer risk factors. Methods. Data were pooled from 2 centers, the Montreal General Hospital and the Feinberg School of Medicine at Northwestern University in Chicago. For each female cohort member, the probability of developing breast cancer during followup was estimated based on factors (including the indi- vidual’s age, parity, age at first live birth, age of menarche, personal history of benign breast disease, and family history) using the Gail model, an established model for predicting breast cancer risk. The actual occurrence of cancer cases was determined by linkage with regional cancer registries. Results. Of the 583 women in the combined cohort, 5 had been diagnosed with breast cancer prior to cohort entry, and 14 declined participation. In those remaining, 12 cases of breast cancer occurred compared to 5.6 predicted by the Gail model (standardized incidence ratio 2.1, 95% confidence interval: 1.1, 3.7). Thus, after controlling for risk factors, the incidence of breast cancer was elevated. Conclusion. Our data suggest that the risk of breast cancer in our SLE cohort is not completely explained by traditional factors found in the Gail model. Other factors, such as carcinogenic expo- sures (i.e., alkylating agents and immunosuppressive drugs) or the immunologic dysregulation of SLE itself, may be contributory. (J Rheumatol 2003;30:1505–7) Key Indexing Terms: SYSTEMIC LUPUS ERYTHEMATOSUS BREAST CANCER RISK Personal, non-commercial use only. The Journal of Rheumatology Copyright © 2003. All rights reserved. www.jrheum.org Downloaded on October 13, 2021 from