Cigarette smoking increases risk for breast cancer in high-risk breast cancer families

Most epidemiological studies of cigarette smoking and breast cancer have fa iled to demonstrate a strong association. Only one study has been performed on women at high genetic risk, and smoking was reported to be a protective factor. To further explore this observation, we examined the association o f cigarette smoking with the risk of breast cancer in a historical cohort s tudy of high-risk breast cancer families. A total of 426 families ascertain ed through a consecutive series of breast cancer patients (probands) betwee n 1944 and 1952 were followed through 1996. Occurrence of breast cancer and detailed smoking histories for sisters, daughters, granddaughters, nieces, and marry-ins were obtained through telephone interviews between 1991 and 1996. Cox proportional hazards regression, accounting for age, birth cohort , and other risk factors, was used to calculate relative risks and 95% conf idence intervals (CIs) of breast cancer. All of the models were constructed within strata defined by relationship to the index case (proband), with no nsmokers designated as the referent group. Of the 426 families in the cohor t, 132 had at least three incident breast and/or ovarian cancers in the bio logical relatives at the end of the follow-up period. Among sisters and dau ghters in these 132 high-risk families, those who ever smoked were at 2.4-f old increased risk of breast cancer (95% CI, 1.2-5.1) relative to never-smo kers. No association between breast cancer and smoking was observed among n ieces and granddaughters of probands or among marry-ins. When the analysis was restricted to 35 families at highest genetic risk (each containing five breast and/or ovarian cancers), smoking became an even stronger risk facto r. Among sisters and daughters, ever-smokers were at 5.8-fold greater risk than nonsmokers (95% CI, 1.4-23.9). Among nieces and granddaughters, the ri sk of breast cancer associated with smoking was increased 60% (95% CI, 0.8- 3.2). These results suggest that smoking may increase risk for breast cance r in families with multiple cases of breast or ovarian cancer, especially t hose with the strongest apparent familial predisposition.