Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study

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Abstract

Objective To examine the association between smoking and risk of invasive breast cancer using quantitative measures of lifetime passive and active smoking exposure among postmenopausal women.

Design Prospective cohort study.

Setting 40 clinical centres in the United States.

Participants 79 990 women aged 50–79 enrolled in the Women’s Health Initiative Observational Study during 1993–8.

Main outcome measures Self reported active and passive smoking, pathologically confirmed invasive breast cancer.

Results In total, 3520 incident cases of invasive breast cancer were identified during an average of 10.3 years of follow-up. Compared with women who had never smoked, breast cancer risk was elevated by 9% among former smokers (hazard ratio 1.09 (95% CI 1.02 to 1.17)) and by 16% among current smokers (hazard ratio 1.16 (1.00 to 1.34)). Significantly higher breast cancer risk was observed in active smokers with high intensity and duration of smoking, as well as with initiation of smoking in the teenage years. The highest breast cancer risk was found among women who had smoked for ≥50 years or more (hazard ratio 1.35 (1.03 to1.77) compared with all lifetime non-smokers, hazard ratio 1.45 (1.06 to 1.98) compared with lifetime non-smokers with no exposure to passive smoking). An increased risk of breast cancer persisted for up to 20 years after smoking cessation. Among women who had never smoked, after adjustment for potential confounders, those with the most extensive exposure to passive smoking (≥10 years’ exposure in childhood, ≥20 years’ exposure as an adult at home, and ≥10 years’ exposure as an adult at work) had a 32% excess risk of breast cancer compared with those who had never been exposed to passive smoking (hazard ratio 1.32 (1.04 to 1.67)). However, there was no significant association in the other groups with lower exposure and no clear dose response to cumulative passive smoking exposure.

Conclusions Active smoking was associated with an increase in breast cancer risk among postmenopausal women. There was also a suggestion of an association between passive smoking and increased risk of breast cancer.

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Most cited references 66

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Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group.

SR Johnson, M Henderson, C Furberg … (1998)

The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components--dietary modification (DM) or hormone replacement therapy (HRT)--of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.

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Etiology of hormone receptor-defined breast cancer: a systematic review of the literature.

Jennifer H Fergenbaum, Michelle Althuis, Louise Brinton … (2004)

Breast cancers classified by estrogen receptor (ER) and/or progesterone receptor (PR) expression have different clinical, pathologic, and molecular features. We examined existing evidence from the epidemiologic literature as to whether breast cancers stratified by hormone receptor status are also etiologically distinct diseases. Despite limited statistical power and nonstandardized receptor assays, in aggregate, the critically evaluated studies (n = 31) suggest that the etiology of hormone receptor-defined breast cancers may be heterogeneous. Reproduction-related exposures tended to be associated with increased risk of ER-positive but not ER-negative tumors. Nulliparity and delayed childbearing were more consistently associated with increased cancer risk for ER-positive than ER-negative tumors, and early menarche was more consistently associated with ER-positive/PR-positive than ER-negative/PR-negative tumors. Postmenopausal obesity was also more consistently associated with increased risk of hormone receptor-positive than hormone receptor-negative tumors, possibly reflecting increased estrogen synthesis in adipose stores and greater bioavailability. Published data are insufficient to suggest that exogenous estrogen use (oral contraceptives or hormone replacement therapy) increase risk of hormone-sensitive tumors. Risks associated with breast-feeding, alcohol consumption, cigarette smoking, family history of breast cancer, or premenopausal obesity did not differ by receptor status. Large population-based studies of determinants of hormone receptor-defined breast cancers defined using state-of-the-art quantitative immunostaining methods are needed to clarify the role of ER/PR expression in breast cancer etiology.

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Author and article information

Contributors

: Role: assistant professor

: Role: senior clinical investigator

: Role: professor and associate chair

: Role: associate professor, Role: associate center director

: Role: research associate professor

: Role: professor

: Role: assistant professor of medicine

: Role: assistant professor

: Role: professor

Journal

Journal ID (nlm-ta): BMJ

Journal ID (publisher-id): bmj

Title: BMJ : British Medical Journal

Publisher: BMJ Publishing Group Ltd.

ISSN (Print): 0959-8138

ISSN (Electronic): 1468-5833

Publication date Collection: 2011

Publication date (Print): 2011

Publication date (Electronic): 01 March 2011

Volume: 342

Electronic Location Identifier: d1016

Affiliations

[1 ]Department of Community Medicine, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, USA

[2 ]HealthPartners Research Foundation, Box 1524, Mailstop 21111R, Minneapolis, MN 55440-1524, USA

[3 ]Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY, USA

[4 ]WV Prevention Research Center, West Virginia University

[5 ]Department of Preventive Medicine, Stony Brook University, NY, USA

[6 ]Stanford University School of Medicine, CA, USA

[7 ]Center for Research on Health Care, Division of General Internal Medicine, University of Pittsburgh, Pittsburgh, PA, USA

[8 ]Division of General Internal Medicine, University of California, Davis Medical Center, Sacramento, CA, USA

[9 ]Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

Author notes

Corresponding to: K L Margolis Karen.L.Margolis@ 123456HealthPartners.com

Article

Publisher ID: luoj766568

DOI: 10.1136/bmj.d1016

PMC ID: 3047002

PubMed ID: 21363864

SO-VID: 6ea53748-6f59-47e2-95d5-4e05b0199b37

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

Association of active and passive smoking with risk of breast cancer among postmenopausal women: a prospective cohort study

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Most cited references 66

Design of the Women's Health Initiative clinical trial and observational study. The Women's Health Initiative Study Group.

Graphical methods for assessing violations of the proportional hazards assumption in Cox regression.

Etiology of hormone receptor-defined breast cancer: a systematic review of the literature.

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