Snus use,smoking and survival among prostate cancer patients

Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with respect to prostate cancer survival. The study is nested among 9,582 men with incident prostate cancer within a prospective cohort of 336,381 Swedish construction workers. Information on tobacco use was collected at study entry between 1971 and 1992, and categorized into (i) never users of any tobacco, (ii) exclusive snus: ever users of snus only, (iii) exclusive smokers: ever smokers (cigarette, cigar and/or pipe) only and (iv) ever users of both snus and smoking. Hazard ratios for prostate cancer‐specific and total mortality for smoking and snus use based on Cox proportional hazards models adjusted for age, calendar period at diagnosis and body mass index at baseline. During 36 years of follow‐up, 4,758 patients died—2,489 due to prostate cancer. Compared to never users of tobacco, exclusive smokers were at increased risk of prostate cancer mortality (HR 1.15, 95% CI: 1.05–1.27) and total mortality (HR 1.17, 95% CI: 1.09–1.26). Exclusive snus users also had increased risks for prostate cancer mortality (HR 1.24, 95% CI: 1.03–1.49) and total mortality (HR 1.19, 95% CI: 1.04–1.37). Among men diagnosed with nonmetastatic disease, the HR for prostate cancer death among exclusive snus users was 3.17 (95% CI: 1.66–6.06). The study is limited by a single assessment of tobacco use prior to diagnosis. Snus use was associated with increased risks of prostate cancer and total mortality among prostate cancer patients. This suggests that tobacco‐related components such as nicotine or tobacco‐specific carcinogens may promote cancer progression independent of tobacco's combustion products.     

Use of moist oral snuff (snus) and pancreatic cancer: Pooled analysis of nine prospective observational studies

While smoking is a well‐established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person‐years of observation, 1,447 men developed pancreatic cancer. Compared to never‐snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.     

A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively,compared with no use of tobacco

The main objective of this systematic review was to assess cancer risk, and mortality after cancer diagnosis, for exclusive users of Swedish snus, compared with non-users of tobacco. We followed international standards for systematic reviews and graded our confidence in the risk estimates using the GRADE approach. Our search gave 2450 articles, of which 67 were assessed in full text against our inclusion criteria. Of these, 14 cohort-studies and one case-control study were included in the review. The studies investigated risk of cancer in the oral cavity or oropharynx (3 studies), esophagus (1 study), stomach (1 study), pancreas (2 studies), colorectum (2 studies), anus (1 study) and lung (1 study), as well as malignant lymphoma (1 study), leukemia and multiple myeloma (1 study), melanoma (1 study), any cancer (1 study) and mortality after cancer diagnosis (4 studies). Cancer risk could only be evaluated in men as there was a general lack of data for women. All included studies were evaluated to have a moderate risk of bias, mostly related to validity of exposure information. An increased risk of cancer of the esophagus, pancreas, stomach and rectum as well as an association between use of snus and increased mortality after a cancer diagnosis was reported. Our confidence in the various risk estimates varied from moderate through low to very low.     

Tobacco smoking, snuff dipping and the risk of cutaneous squamous cell carcinoma: a nationwide cohort study in Sweden

We investigated whether tobacco use causes cutaneous squamous cell carcinoma (CSCC) in a large cohort study with complete and long-term follow-up. A total of 756 incident cases occurred in a cohort of 337,311 men during a 30-year follow-up period, but no association was found between any kind of smoking tobacco use and CSCC risk, nor any risk change with increasing dose, duration or time since smoking cessation. Snuff use was associated with a decreased risk of CSCC. Overall, our study provides no evidence that tobacco use increases the risk of CSCC.     

Tobacco use and cancer survival: A cohort study of 40,230 Swedish male construction workers with incident cancer

On theoretical grounds, nicotine has been implicated as a modifier of cancer progression. We investigated possible associations of smoking or use of Scandinavian moist snuff (snus) with survival after cancer among Swedish male construction workers. Snus use is associated with substantial exposure to nicotine but not to the combustion products in smoke. Among 336,381 workers with detailed information on tobacco use in 1971–1992, we observed 40,230 incident cancers. Complete follow‐up through 2007 was accomplished through linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) for death from any cause, cancer‐specific death and death from other causes were derived from Cox proportional hazards regression models adjusted for age at diagnosis, body mass index at study entry and period of diagnosis. Never users of any tobacco served as reference. Increased risks of cancer‐specific death were observed both among exclusive smokers (HR_{all cancer} 1.15, 95% CI: 1.10–1.21) and never‐smoking snus users (1.15, 95% CI: 1.05–1.26). As regards deaths due to other causes, exclusive smokers had higher relative risks than exclusive snus users (p = 0.03). A history of tobacco use, even exclusive use of the seemingly benign snus, is associated with moderately increased cancer‐specific mortality. Although nicotine might play a role, the mechanisms warrant further investigation.     

Risk of gastric cancer among smokers infected with Helicobacter pylori

Infection with the gastric bacterium Helicobacter pylori (in particular infection with CagA-positive strains) and smoking have been identified as risk factors for the development of gastric cancer. Both risk factors are typically acquired early in life and prevail over decades if not for life. We assessed the individual and joint impact of both risk factors on gastric cancer risk in a population-based case-control study from Germany including 71 patients with histologically verified gastric cancer and 363 patients with colorectal cancer who served as controls. Information on smoking and potential confounding factors was collected by standardized interviews. H. pylori infection was measured serologically by immunoglobulin G antibody titers against H. pylori. In addition, antibodies against the CagA antigen were determined by Western blot. Twenty-seven percent of cases compared with 15% of controls were smokers, and 43% of cases compared with 23% of controls were infected with CagA-positive H. pylori strains. After control for potential confounders, the relative risk of gastric cancer was 2.6 (95% CI 1.2-5.7) for nonsmoking subjects with CagA-positive H. pylori infections and 7.2 (95% CI 2.2-23.6) for smoking subjects with CagA-positive H. pylori infections compared with subjects without these risk factors. The corresponding relative risks for noncardia gastric cancer were 6.1 ( 95% CI 2.3-16.5) and 16.6 (95% CI 4.3-64.2). We conclude that smoking subjects with CagA-positive H. pylori infections have a strongly increased risk of gastric cancer and may be an important group for targeting efforts of prevention and early detection.     

Smoking cessation and lung cancer risk in an Asian population: Findings from the Singapore Chinese Health Study

Background:

Smoking cessation is an important strategy for reducing the harmful effects of tobacco, particularly in the prevention of lung cancer; however, prospective data on the impact of smoking cessation on lung cancer risk in Asian populations are limited.

Methods:

We studied a population-based cohort of Chinese men and women aged 45–74 years – participants of the Singapore Chinese Health Study. Information on smoking, lifestyle and dietary habits was collected at the time of recruitment in 1993–1998; and smoking status was assessed again at a second interview in 1999–2004 (mean interval 5.8 years). Participants were followed up to 31 December 2007, and incident cases of lung cancer were ascertained by linkage with population-wide registries.

Results:

Among 45 900 participants, there were 463 incident cases of lung cancer. Relative to current smokers, those who quit smoking subsequent to baseline assessment had a 28% decrease in the risk of lung cancer (adjusted hazard ratio (HR) 0.72; 95% CI (95% confidence interval): 0.53–0.98). The risk was less than half in ex-smokers who had quit before the first interview and maintained their status (HR 0.42; 95% CI: 0.32–0.56).

Conclusions:

Reduction in lung cancer incidence with smoking cessation in Asian populations is substantial and can be observed within a few years after quitting.     

A snapshot of smokers after lung and colorectal cancer diagnosis

BACKGROUND:

Continued smoking after a cancer diagnosis may adversely affect treatment effectiveness, subsequent cancer risk, and survival. The prevalence of continued smoking after cancer diagnosis is understudied.

METHODS:

In the multi‐regional Cancer Care Outcomes Research and Surveillance cohort (lung cancer [N = 2456], colorectal cancer [N = 3063]), the authors examined smoking rates at diagnosis and 5 months after diagnosis and also study factors associated with continued smoking.

RESULTS:

Overall, 90.2% of patients with lung cancer and 54.8% of patients with colorectal cancer reported ever smoking. At diagnosis, 38.7% of patients with lung cancer and 13.7% of patients with colorectal cancer were smoking; whereas, 5 months after diagnosis, 14.2% of patients with lung cancer and 9.0% of patients with colorectal cancer were smoking. Factors that were associated independently with continued smoking among patients with nonmetastatic lung cancer were coverage by Medicare, other public/unspecified insurance, not receiving chemotherapy, not undergoing surgery, prior cardiovascular disease, lower body mass index, lower emotional support, and higher daily ever‐smoking rates (all P < .05). Factors that were associated independently with continued smoking among patients with nonmetastatic colorectal cancer were male sex, high school education, being uninsured, not undergoing surgery, and higher daily ever‐smoking rates (all P < .05).

CONCLUSIONS:

After diagnosis, a substantial minority of patients with lung and colorectal cancers continued smoking. Patients with lung cancer had higher rates of smoking at diagnosis and after diagnosis; whereas patients with colorectal cancer were less likely to quit smoking after diagnosis. Factors that were associated with continued smoking differed between lung and colorectal cancer patients. Future smoking‐cessation efforts should examine differences by cancer type, particularly when comparing cancers for which smoking is a well established risk factor versus cancers for which it is not. Cancer 2012;118: 3153–64. © 2012 American Cancer Society.     

Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer

Hypermethylation of cytosines in CpG-rich islands of the promoter regions of regulatory genes has been discovered as a common mechanism of gene silencing during carcinogenesis. We analysed 64 primary lung carcinomas for promoter methylation of the tumour suppressor genes (TSGs) p16 (p16(INK4a)/CDKN2A) and p14 (p14(ARF)) by methylation-specific PCR, in order to evaluate aberrant methylation as a potential biomarker for epigenetic alterations in tobacco-related lung cancer. Methylation of p16 was observed in 34% (22/64) of the lung tumours examined. In particular, p16 methylation occurred in nonsmall cell lung cancer (NSCLC) only, with 41 % (22/54) of the tumours being positive. The highest frequency was found in large cell carcinoma (5/7, 71%), followed by adenocarcinoma (9/25, 36%) and squamous cell carcinoma (7/21, 33%). Methylation of the p14 gene was less frequent in lung cancer (4/52, 8%). When association with tobacco smoking was analysed, 42% (21/50) of NSCLC from ever smokers exhibited p16 methylation. Interestingly, the analysis revealed a significantly higher risk of p16 methylation in former smokers as compared to current smokers [odds ratio (OR) 5.1; 95% confidence interval (CI) 1.3-22]. The difference was retained after adjustment for age (OR 3.7; 95% CI 0.9-17). The promoter methylation results were then combined with data on genetic alterations determined previously in the same set of tumours. This data similarly showed that p16 methylation in parallel with p53 gene mutation or p14 methylation occurred more frequently in former smokers than in current smokers (44% vs. 14%; P = 0.035). Taken together, our data suggest that analysis of promoter methylation in TSGs may provide a valuable biomarker for identification of groups with an elevated risk of cancer, such as smokers and ex-smokers.     

Reduced risk of prostate cancer among patients with diabetes mellitus

Although diabetes mellitus is associated with an increased risk of several malignancies, a negative association with prostate cancer is biologically most plausible. The epidemiologic evidence is, however, inconsistent, limited and based mostly on small studies. We present results from a large, population-based cohort study in Sweden, where we assessed prostate cancer risk among patients hospitalized for diabetes mellitus. The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIRs), with 95% confidence interval (CI), were used as a measure of relative risk. After complete exclusion of the first year of follow-up (to avoid selection bias), 135,950 men remained in the cohort, contributing 827,099 years of follow-up to the study. A total of 2,455 incident cases of primary prostate cancer were identified during 1-31 years of follow-up, yielding an overall SIR of 0.91 (95% CI 0.87-0.94); this risk reduction was more pronounced among patients who have been hospitalized for diabetic complications (SIR = 0.82; 95% CI 0.74-0.91). We found no consistent trends in risk related to age at first hospitalization or to duration of follow-up. We did find a small, but significantly decreased risk of prostate cancer among men who had been hospitalized for diabetes mellitus.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.     

Risk of second cancer among women with breast cancer

A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI = 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR = 1.35), colorectal (SIR = 1.22), lung (SIR = 1.24), soft tissue sarcoma (SIR = 2.25), melanoma (SIR = 1.29), non-melanoma skin (SIR = 1.58), endometrium (SIR = 1.52), ovary (SIR = 1.48), kidney (SIR = 1.27), thyroid gland (SIR = 1.62) and leukaemia (SIR = 1.52). The excess of cancer after a breast cancer diagnosis is likely to be explained by treatment for breast cancer and by shared genetic or environmental risk factors, although the general excess of cancer suggests that there may be additional explanations such as increased surveillance and general cancer susceptibility.     

Risk of lung cancer from environmental exposures to tobacco smoke

Epidemiologic evidence on the relation between environmental tobacco smoke and cancer is reviewed. The labeling of tobacco smoke as an environmental cause of lung cancer has been challenged based on allegations of bias in the epidemiologic data. However, tobacco smoke has been shown to increase the risk of lung cancer down to the lowest exposure levels. Environmental tobacco smoke contains the same carcinogenic compounds as those found in the tobacco smoke inhaled directly by the smoker. Nonsmokers environmentally exposed have elevated levels of tobacco smoke byproducts in biological samples. These observations alone are sufficient to identify tobacco smoke as an environmental carcinogen. The epidemiologic studies showing that environmental exposure to tobacco smoke is associated weakly but consistently with increased risk of lung cancer. While these epidemiologic studies have been challenged, it does not appear that the observed epidemiologic associations are due to misclassification or confounding. Indeed, the epidemiologic results, particularly among the studies with superior data collection methods and better control of bias and confounding, find consistent associations between environmental tobacco smoke and lung cancer. This paper summarizes the evidence that environmental exposure to tobacco smoke increases the risk of lung cancer, and considers the criticisms of the epidemiologic evidence which have been raised.     

Trends in urinary bladder cancer incidence in Sweden 1960-93 with special reference to histopathology, time period, birth cohort, and smoking

This study investigates the incidence trends of urinary bladdercancer in Sweden from 1960 through 1993 (a total of 46,211 cases).Age-standardized incidence rates increased among men from 14.6 per 10 5 in1960 to 33.5 in 1993 and among women from4.8 to 8.8, corresponding to anaverage annual increase of 2.4 percent (95 percent confidence interval [CI])= 2.0-2.7 percent) and 1.1 percent (CI = 0.9-1.4 percent), respectively. Thelargest increase occurred in the oldest age-groups. The proportion ofpatients with transitional cell carcinoma increased in menfrom66.0 percent in1960-64 to 93.6 percent in 1990-93 and in women from 61.0 percent to 89.4percent. The proportion of patients with papillomas decreased, whereas thosewith adenocarcinoma and squamous cell carcinoma were stable. Regressionmodeling (based on the period 1960-89) showed a strong linear effect due toeither period and/or cohort. Among men, additional non-linear effects by bothperiod and cohort were obtained. T he cohort effects were more important.Cohort data on having smoked daily showed considerable similarities with theestimated cohort-effects. Our findings suggest that the increase of tobaccosmoking in successive generations can explain the increase in incidence ratesof bladder cancer in Sweden, whereas improved diagnostic activities andregistration are less likely to explain fully the changes in incidence rates.     

Predictors of smoking relapse in patients with thoracic cancer or head and neck cancer

BACKGROUND:

Cancer patients who continue smoking are at increased risk for adverse outcomes including reduced treatment efficacy and poorer survival rates. Many patients spontaneously quit smoking after diagnosis; however, relapse is understudied. The goal of this study was to evaluate smoking‐related, affective, cognitive, and physical variables as predictors of smoking after surgical treatment among patients with lung cancer and head and neck cancer.

METHODS:

A longitudinal study was conducted with 154 patients (57% male) who recently quit smoking. Predictor variables were measured at baseline (ie, time of surgery); smoking behavior was assessed at 2, 4, 6, and 12 months after surgery. Analyses of 7‐day point prevalence were performed using a Generalized Estimating Equations approach.

RESULTS:

Relapse rates varied significantly depending on presurgery smoking status. At 12 months after surgery, 60% of patients who smoked during the week prior to surgery had resumed smoking versus only 13% who were abstinent prior to surgery. Smoking rates among both groups were relatively stable across the 4 follow‐ups. For patients smoking before surgery (N = 101), predictors of smoking relapse included lower quitting self‐efficacy, higher depression proneness, and greater fears about cancer recurrence. For patients abstinent before surgery (N = 53), higher perceived difficulty quitting and lower cancer‐related risk perceptions predicted smoking relapse.

CONCLUSIONS:

Efforts to encourage early cessation at diagnosis, and increased smoking relapse‐prevention efforts in the acute period following surgery, may promote long‐term abstinence. Several modifiable variables are identified to target in future smoking relapse‐prevention interventions for cancer patients. Cancer 2013. © 2012 American Cancer Society.     

Passive smoking and breast cancer risk among non-smoking Chinese women

Our purpose was to evaluate whether passive exposure to cigarette smoke may be related to breast cancer risk. Data from the Shanghai Breast Cancer Study, a large population-based study of 1459 breast cancer cases and 1556 controls aged 25-64 years, were analyzed. Respective response rates were 91.1% and 90.3%. Passive smoking questions were added to all face-to-face interviews 7 months into the study. Women were asked about exposure to their husbands' smoke at home as well as exposure in the workplace. Analyses were restricted to the 1013 cases and 1117 controls with passive tobacco smoke exposure data who had never actively smoked. Over 60% of controls reported some exposure to a husband's smoke and over 40% reported exposure to passive smoke in the workplace. Overall, there was no apparent association between any passive smoke exposure or exposure to a husband's smoke and breast cancer risk. There was some evidence of an elevated breast cancer risk associated with passive smoking exposure of 5 hr or more per day in the workplace (OR = 1.6, 95% confidence interval 1.0-2.4; p for trend = 0.02). This association warrants further investigation.     

Risk of thyroid cancer among Iranian immigrants in Sweden

Objectives: Studies of immigrants are of value to elucidate the role of environmental factors in cancer causation, but large cohorts are needed in order to study rare cancers. We conducted a register-based study of a cohort of 59,274 (32,236 men and 27,038 women) Swedish residents born in Iran, with follow-up between 1969 and 2004. We identified 50 incident cases of thyroid cancer during more than 800 thousands person-years of observation. Methods: Rate ratios (RR) were calculated based on Poisson models estimated by the maximum likelihood method, using Swedish born residents with both parents born in Sweden as reference population. 95% confidence interval was estimated on the assumption that the observed numbers of cancers follow a Poisson distribution. Results: The adjusted RR of thyroid cancer among Iranian immigrants was 2.6 (95% CI 2.0–3.5), without appreciable sex differences. In both sexes, the excess risk was highest among people who were younger than 30 years at immigration. Among women, the largest excess risk (adjusted RR = 4.6, 95% CI 2.9–7.4) was observed during the first 5 years from immigration, while for men, during the second decade from immigration. The rateratio was higher among subjects who immigrated before 1990 (adjusted RR = 2.7, 95% CI 2.0–3.8) than among those immigrated thereafter, particularly among men. Conclusion: The observed excess risk among Iranian immigrants compared to Swedish-born residents is compatible with differential burden of environmental risk factors, the most likely of which are iodine deficiency and high natural levels of ionizing radiation.     

Optimal management of gastroesophageal junction cancer

Although recent decades have witnessed incremental improvements in the treatment of gastroesophageal junction (GEJ) carcinoma, outcomes remain modest. For locally advanced esophageal cancer, the addition of chemotherapy and/or radiation to surgery is considered the standard of care. Chemotherapy remains the primary treatment for metastatic disease and improves survival over best supportive care. However, the prognosis for patients with GEJ cancers, which are treated along the same paradigms as esophageal and gastric carcinomas, remain poor because of the emergence of chemoresistance and limited targeted therapeutic approaches, which include agents that target the HER2 and vascular endothelial growth factor pathways. Evaluation of immune checkpoint inhibitors in the chemorefractory setting have confirmed the activity of immunotherapy in esophagogastric cancer. Ongoing immunotherapeutic strategies are being evaluated in both the locally advanced and metastatic settings. This review focuses on the treatment of locally advanced and metastatic GEJ carcinomas, which encompass all tumors that have an epicenter within 5 cm proximal or distal to the anatomical Z-line (Siewert classification). Because the vast majority of GEJ tumors are adenocarcinoma, the management of adenocarcinoma is the focus of this review. Evolving approaches and areas of clinical equipoise are discussed.     

Active cigarette smoking and risk of breast cancer

Although epidemiological evidence on the role of active cigarette smoking in breast cancer risk has been inconsistent, recent literature supports a modest association between smoking and breast cancer. This association is particularly observed in women who smoke for a long duration, or who smoke for a long time prior to their first pregnancy. Here, we provide updated results on cigarette smoking and breast cancer risk in the Canadian National Breast Screening Study (NBSS). The NBSS is a large cohort of 89,835 women, aged 40–59, who were followed for a mean of 22.1 years, resulting in the ascertainment of 6,549 incident cases of breast cancer. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of cigarette smoking variables with breast cancer risk. We found breast cancer to be associated with duration (40 years vs. 0: HR = 1.57; 95%CI = 1.29–1.92), intensity (40 cigarettes per day vs. 0: HR = 1.21; 95%CI = 1.04–1.40), cumulative exposure (40 pack‐years vs. 0: HR = 1.19; 95%CI = 1.06–1.13) and latency (40 years since initiation vs. 0: HR = 1.19; 95%CI = 1.10–1.53) of cigarette smoking. Number of years smoked prior to first full‐term pregnancy was associated with higher risk of breast cancer than comparative years smoked post‐pregnancy (among parous women, 5 years pre pregnancy vs. 0: HR = 1.18; 95%CI = 1.10–1.26). These results strongly support a role for cigarette smoking in breast cancer etiology and emphasize the importance of timing of this exposure.