PMC:13911 / 1223-8494 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/13911","sourcedb":"PMC","sourceid":"13911","source_url":"http://www.ncbi.nlm.nih.gov/pmc/13911","text":"Introduction:\nOverall, epidemiological studies [1,2,3,4] have \t\t\t\treported no substantial association between cigarette smoking and the risk of \t\t\t\tbreast cancer. Some studies [5,6,7] reported a significant increase of \t\t\t\tbreast cancer risk among smokers. In recent studies that addressed the \t\t\t\tassociation between breast cancer and cigarette smoking, however, there was \t\t\t\tsome suggestion of a decreased risk [8,9,10], especially among current smokers, \t\t\t\tranging from approximately 10 to 30% [9,10]. Brunet et al [11] \t\t\t\treported that smoking might reduce the risk of breast cancer by 44% in carriers \t\t\t\tof BRCA1 or BRCA2 gene mutations. Wolfe [12] described four different mammographic patterns created by \t\t\t\tvariations in the relative amounts of fat, epithelial and connective tissue in \t\t\t\tthe breast, designated N1, P1, P2 and DY. Women with either P2 or DY pattern \t\t\t\tare considered at greater risk for breast cancer than those with N1 or P1 \t\t\t\tpattern [12,13,14,15]. There are no published studies \t\t\t\tthat assessed the relationship between smoking and mammographic parenchymal \t\t\t\tpatterns.\n\nAims:\nTo evaluate whether mammographic parenchymal patterns as \t\t\t\tclassified by Wolfe, which have been positively associated with breast cancer \t\t\t\trisk, are affected by smoking. In this case-control study, nested within the \t\t\t\tEuropean Prospective Investigation on Cancer in Norfolk (EPIC-Norfolk) cohort \t\t\t\t[16], the association between smoking habits and \t\t\t\tmammographic parenchymal patterns are examined. The full results will be \t\t\t\tpublished elsewhere.\n\nMethods:\nStudy subjects were members of the EPIC cohort in Norwich who also \t\t\t\tattended the prevalence screening round at the Norwich Breast Screening Centre \t\t\t\tbetween November 1989 and December 1997, and were free of breast cancer at that \t\t\t\tscreening. Cases were defined as women with a P2/DY Wolfe's mammographic \t\t\t\tparenchymal pattern on the prevalence screen mammograms. A total of 203 women \t\t\t\twith P2/DY patterns were identified as cases and were individually matched by \t\t\t\tdate of birth (within 1 year) and date of prevalence screening (within 3 \t\t\t\tmonths) with 203 women with N1/P1 patterns who served as control \t\t\t\tindividuals.\nTwo views, the mediolateral and craniocaudal mammograms, of both \t\t\t\tbreasts were independently reviewed by two of the authors (ES and RW) to \t\t\t\tdetermine the Wolfe mammographic parenchymal pattern.\nConsiderable information on health and lifestyle factors was \t\t\t\tavailable from the EPIC Health and Lifestyle Questionnaire [16]. In the present study we examined the subjects' personal \t\t\t\thistory of benign breast diseases, menstrual and reproductive factors, oral \t\t\t\tcontraception and hormone replacement therapy, smoking, and anthropometric \t\t\t\tinformation such as body mass index and waist:hip ratio.\nOdds ratios (ORs) and their 95% confidence intervals (CIs) were \t\t\t\tcalculated by conditional logistic regression [17], and \t\t\t\twere adjusted for possible confounding factors.\n\nResults:\nThe characteristics of the cases and controls are presented in \t\t\t\tTable 1. Cases were leaner than controls. A larger \t\t\t\tpercentage of cases were nulliparous, premenopausal, current hormone \t\t\t\treplacement therapy users, had a personal history of benign breast diseases, \t\t\t\tand had had a hysterectomy. A larger proportion of controls had more than three \t\t\t\tbirths and were current smokers.\nTable 2 shows the unadjusted and adjusted OR \t\t\t\testimates for Wolfe's high-risk mammographic parenchymal patterns and smoking \t\t\t\tin the total study population and in postmenopausal women separately. Current \t\t\t\tsmoking was strongly and inversely associated with high-risk patterns, after \t\t\t\tadjustment for concomitant risk factors. Relative to never smokers, current \t\t\t\tsmokers were significantly less likely to have a high-risk pattern (OR 0.37, \t\t\t\t95% CI 0.14-0.94). Similar results were obtained when the analysis was confined \t\t\t\tto postmenopausal women. Past smoking was not related to mammographic \t\t\t\tparenchymal patterns. The overall effect in postmenopausal women lost its \t\t\t\tsignificance when adjusted for other risk factors for P2/DY patterns that were \t\t\t\tfound to be significant in the present study, although the results were still \t\t\t\tstrongly suggestive. There was no interaction between cigarette smoking and \t\t\t\tbody mass index.\n\nDiscussion:\nIn the present study we found a strong inverse relationship \t\t\t\tbetween current smoking and high-risk mammographic parenchymal patterns of \t\t\t\tbreast tissue as classified by Wolfe [12]. These \t\t\t\tfindings are not completely unprecedented; Greendale et al [18] found a reduced risk of breast density in association with \t\t\t\tsmoking, although the magnitude of the reduction was unclear. The present \t\t\t\tfindings suggest that this reduction is large.\nRecent studies [9,10] \t\t\t\thave suggested that breast cancer risk may be reduced among current smokers. In \t\t\t\ta multicentre Italian case-control study, Braga et al [10] found that, relative to nonsmokers, current smokers had a \t\t\t\treduced risk of breast cancer (OR 0.84, 95% CI 0.7-1.0). These findings were \t\t\t\trecently supported by Gammon et al [9], who \t\t\t\treported that breast cancer risk in younger women (younger than 45 years) may \t\t\t\tbe reduced among current smokers who began smoking at an early age (OR 0.59, \t\t\t\t95% CI 0.41-0.85 for age 15 years or younger) and among long-term smokers (OR \t\t\t\t0.70, 95% CI 0.52-0.94 for those who had smoked for 21 years or more).\nThe possible protective effect of smoking might be due to its \t\t\t\tanti-oestrogenic effect [1,2,19]. Recently there has been renewed interest in the potential \t\t\t\teffect of smoking on breast cancer risk, and whether individuals may respond \t\t\t\tdifferently on the basis of differences in metabolism of bioproducts of smoking \t\t\t\t[20,21]. Different relationships \t\t\t\tbetween smoking and breast cancer risk have been suggested that are dependent \t\t\t\ton the rapid or slow status of acetylators of aromatic amines [20,21]. More recent studies [22,23], however, do not support these \t\t\t\tfindings.\nThe present study design minimized the opportunity for bias to \t\t\t\tinfluence the findings. Because subjects were unaware of their own case-control \t\t\t\tstatus, the possibility of recall bias in reporting smoking status was \t\t\t\tminimized. Systematic error in the assessment of mammograms was avoided because \t\t\t\treading was done without knowledge of the risk factor data. Furthermore, the \t\t\t\tassociations observed are unlikely to be explained by the confounding effect of \t\t\t\tother known breast cancer risk factors, because we adjusted for these in the \t\t\t\tanalysis. We did not have information on passive smoking status, however, which \t\t\t\thas recently been reported to be a possible confounder [5,6,21,24].\nThe present data indicate that adjustment for current smoking \t\t\t\tstatus is important when evaluating the relationship between mammographic \t\t\t\tparenchymal pattern and breast cancer risk. They also indicate smoking as a \t\t\t\tprominent potential confounder when analyzing effects of other risk factors \t\t\t\tsuch as obesity-related variables. It seems that parenchymal patterns may act \t\t\t\tas an informative biomarker of the effect of cigarette smoking on breast cancer \t\t\t\trisk. 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