Pack‐years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer

BACKGROUND:

This study was undertaken to characterize the relation between the survival of patients with stage IIIB/IV nonsmall cell lung cancer (NSCLC) and pack‐years of cigarette smoking (graded according to the American Joint Committee on Cancer staging system).

METHODS:

Data were analyzed from patients with stage IIIB/IV NSCLC who had completed a prospective smoking questionnaire. The impact of pack‐years of cigarette smoking, age, sex, Karnofsky performance status (KPS), and the presence of weight loss >5% was evaluated on overall survival using univariate and multivariate analyses.

RESULTS:

Smoking history and clinical data were available for 2010 patients with stage IIIB/IV NSCLC (1004 women and 1006 men). Approximately 70% of patients (1409 patients) had smoked >15 pack‐years, 13% (270) were former and current smokers who had smoked ≤15 pack‐years, and 16% (331) were never‐smokers (<100 lifetime cigarettes). Never‐smokers had a longer median survival compared with former or current smokers (17.8 months vs 11.3 months; log?rank P < .001). Among smokers, patients with a ≤15 pack‐year history of smoking had a longer median survival than patients who had smoked >15 pack‐years (14.6 months vs 10.8 months; log?rank P = .03). As the number of pack‐years increased, the median overall survival decreased (log?rank P < .001). Multivariate analysis indicated that a history of smoking was an independent prognostic factor (hazard ratio, 1.36; P < .001).

CONCLUSIONS:

More cigarette smoking, measured in pack‐years, was associated with decreased survival after a diagnosis of stage IIIB/IV NSCLC. Trials assessing survival in patients with stage IIIB/IV NSCLC should report a detailed cigarette smoking history for all patients. Cancer 2010. © 2009 American Cancer Society.     

Alcohol,smoking, and risk of Her2‐overexpressing and triple‐negative breast cancer relative to estrogen receptor‐positive breast cancer

Epidemiological evidence is limited on how alcohol consumption and smoking are associated with risk of different subtypes of breast cancer, such as triple‐negative (TN) and human epidermal growth factor receptor 2‐overexpressing (H2E) breast cancers, which may have different etiologies from more common luminal (estrogen receptor [ER+]) breast cancers. In this population‐based case‐case study, we evaluated the association between alcohol, smoking, and risk of H2E and TN breast cancer, compared with ER+ breast cancers, among women aged 20–69 years. Using polytomous regression, associations between alcohol consumption, smoking, and breast cancer risk were evaluated in 909 ER+, 1,290 TN, and 489 H2E breast cancer patients, with ER+ breast cancer patients as the reference group. Current alcohol consumption at diagnosis was associated with a lower risk of H2E breast cancer (odds ratio = 0.74, 95% confidence interval: 0.58–0.92) relative to ER+ cancers. No difference in association was observed by menopausal status. No association between alcohol consumption and TN breast cancer relative to ER+ breast cancer was observed. Women who smoked did not have an altered risk of TN or H2E breast cancer, relative to ER+ cancer. Our results suggest that alcohol is associated with lower risk of H2E breast cancer relative to ER+ breast cancer. This study adds to the body of epidemiologic evidence that breast cancer etiology differs by breast cancer subtype.     

Tobacco smoking, NAT2 acetylation genotype and breast cancer risk

The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers.     

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.     

The effect of population‐based mammography screening in Dutch municipalities on breast cancer mortality: 20 years of follow‐up

Long‐term follow‐up data on the effects of screening are scarce, and debate exists on the relative contribution of screening versus treatment to breast cancer mortality reduction. Our aim was therefore to assess the long‐term effect of screening by age and time of implementation. We obtained data on 69,630 breast cancer deaths between 1980 and 2010 by municipality (N = 431) and age of death (40–79) in the Netherlands. Breast cancer mortality trends were analyzed by defining the municipality‐specific calendar year of introduction of screening as Year 0. Additionally, log‐linear Poisson regression was used to estimate the turning point in the trend after Year 0, per municipality, and the annual percentage change (APC) before and after this point. Twenty years after introduction of screening breast cancer mortality was reduced by 30% in women aged 55–74 and by 34% in women aged 75–79, compared to Year 0. A similar and significant decrease was present in municipalities that started early (1987–1992) and late (1995–1997) with screening, despite the difference in availability of effective adjuvant treatment. In the age groups 55–74 and 75–79, the turning point in the trend in breast cancer mortality was estimated in Years 2 and 6 after the introduction of screening, respectively, after which mortality decreased significantly by 1.9% and 2.6% annually. These findings show that the implementation of mammography screening in Dutch municipalities is associated with a significant decline in breast cancer mortality in women aged 55–79, irrespective of time of implementation.     

Cigarette smoking and breast cancer risk: a population-based study in Sweden

In a Swedish population-based case-control study, smoking showed no convincing association with risk of postmenopausal breast cancer - regardless of timing or level of smoking exposure - either overall or among subgroups.     

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.     

Active and passive smoking and the risk of breast cancer in women aged 36-45 years: a population based case-control study in the UK

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case-control study of breast cancer in women aged 36-45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72-1.73) for past smokers and RR of 1.19 (95% CI 0.72-1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64-1.25), in past smokers, RR of 1.09 (95% CI 0.75-1.56), or in current smokers, RR of 0.93 (95% CI 0.67-1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.     

Alcohol consumption and cigarette smoking in combination: A predictor of contralateral breast cancer risk in the WECARE study

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.     

Husband's smoking status and breast cancer risk in Japan: From the Takayama study

The effects of smoking on breast cancer remain unclear. We assessed the associations of subjects' or husbands' smoking status with breast cancer incidence in a population‐based prospective study in Japan. The subjects were 15 719 women aged 35 years or older. The follow up was conducted from September 1992 to March 2008. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Breast cancer was defined as code C50 according to the International Classification of Diseases and Health Related Problems, 10th Revision. Lifestyle, including smoking status, was assessed with a self‐administered questionnaire. Alcohol consumption was assessed with a validated food‐frequency questionnaire. After multivariate adjustments for age, body mass index, alcohol consumption, physical activity, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy, active smoking was not associated with the risk of breast cancer. Compared with never smokers whose husband had never smoked, the risks of breast cancer were 1.98 (95% CI: 1.03–3.84) among never smokers whose husband was a current smoker of 21 cigarettes per day or more. The increased risk of breast cancer among women having a smoking husband was pronounced among those who did not habitually consume alcohol. These results suggest that exposure to smoke from husbands is a potential risk factor for breast cancer. The impact of alcohol consumption on the increased breast cancer risk from passive smoking needs to be addressed in further studies.     

Mortality from cancer in relation to smoking: 50 years observations on British doctors

A total of 34,439 male British doctors, who reported their smoking habits in November 1951, were followed, with periodic up date of changes in their habits, until death, emigration, censoring. or November 2001. Information was obtained about their mortality from 28 of the 30 types of cancer in men reviewed by the International Agency for Research on Cancer (no death was recorded from the other two). In all, 11 of the 13 types in men that the Agency classed as liable to be caused by smoking were significantly related to smoking and the findings for the other two, which caused only few deaths, suggested they might be. Of the 13 types in men for which the Agency found only sparse or inconsistent data and for which we had data, only two appeared to be possibly related (one positively, one negatively), and the 638 deaths for the summed group were clearly unrelated to smoking. Of the two types for which the Agency thought that the relationship with smoking might be due to bias or confounding, the findings for one (prostate cancer) tended to support the belief that smoking was unrelated, and those for the other (colorectal cancer) showed a weak relationship with smoking, which (in a small subset) could not be attributed to confounding with the consumption of alcohol.     

Active and passive smoking with breast cancer risk for Chinese females:a systematic review and meta-analysis

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especial y for Chinese females. Thus, we systematical y searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases （PubMed, Embase, ScienceDirect, and Wiley） and three Chinese databases （CNKI, WanFang, and VIP）. Fifty-one articles （3 cohort studies and 48 case-control studies） covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio （OR）： 1.62; 95% confidence interval （CI）： 1.39-1.85; I2 = 75.8%, P 〈 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer （OR：1.04;95%CI：0.89-1.20;I2=13.9%, P=0.248;n=31）. The OR of exposure to husband’s smoking and to smoke in the workplace was 1.27 （95% CI： 1.07-1.50） and 1.66 （95% CI： 1.07-2.59）, respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband’s smoke （〈20 and≥20 cigarettes per day）, and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace （〈300 and≥300 min of exposure per day）. These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband’s smoking.     

SULT1A1 genotype, active and passive smoking, and breast cancer risk by age 50 years in a German case-control study

IntroductionSulfotransferase 1A1 (encoded by SULT1A1) is involved in the metabolism of procarcinogens such as heterocyclic amines and polycyclic aromatic hydrocarbons, both of which are present in tobacco smoke. We recently reported a differential effect of N-acetyltransferase (NAT) 2 genotype on the association between active and passive smoking and breast cancer. Additional investigation of a common SULT1A1 genetic polymorphism associated with reduced enzyme activity and stability might therefore provide deeper insight into the modification of breast cancer susceptibility.MethodsWe conducted a population-based case–control study in Germany. A total of 419 patients who had developed breast cancer by age 50 years and 884 age-matched control individuals, for whom risk factor information and detailed smoking history were available, were included in the analysis. Genotyping was performed using a fluorescence-based melting curve analysis method. Multivariate logistic regression analysis was used to estimate breast cancer risk associated with the SULT1A1 Arg²¹³His polymorphism alone and in combination with NAT2 genotype in relation to smoking.ResultsThe overall risk for breast cancer in women who were carriers of at least one SULT1A1*2 allele was not significantly different from that for women with the SULT1A1*1/*1 genotype (adjusted odds ratio 0.83, 95% confidence interval 0.66–1.06). Risk for breast cancer with respect to several smoking variables did not differ substantially between carriers of the *2 allele and noncarriers. However, among NAT2 fast acetylators, the odds ratio associated with passive smoking only (3.23, 95% confidence interval 1.05–9.92) was elevated in homozygous carriers of the SULT1A1*1 allele but not in carriers of the SULT1A1*2 allele (odds ratio 1.28, 95% confidence interval 0.50–3.31).ConclusionWe found no evidence that the SULT1A1 genotype in itself modifies breast cancer risk associated with smoking in women up to age 50 years. In combination with NAT2 fast acetylator status, however, the SULT1A1*1/*1 genotype might increase breast cancer risk in women exposed to tobacco smoke.     

Cause‐specific mortality in women with breast cancer in situ

The long‐term mortality remains unknown in women diagnosed with breast cancer in situ (BCIS). Here, we assessed the cause‐specific mortality in BCIS patients. This population‐based cohort study included 12,243 women diagnosed with BCIS in Sweden between 1980 and 2011. Patients were followed until death, emigration, or 31 December 2013, whichever came first. The 30‐year cumulative incidence of breast cancer‐specific mortality was 6.3%, which is considerably lower than 49.7% observed for other‐cause mortality. Women diagnosed with BCIS were more likely to die from breast cancer (standardized mortality ratio [SMR], 3.85; 95% CI, 3.47–4.27) but less likely to die from cardiovascular disease (SMR, 0.88; 95% CI, 0.82–0.95) than women in the general population. Specifically, the SMRs for breast cancer‐specific mortality decreased over time from 5.19 (95% CI, 3.95–6.81) among BCIS diagnosed during 1980–1989 to 3.03 (95% CI, 2.35–3.91) among those diagnosed during 2000–2011. Furthermore, higher risk of death from other causes was seen among those with older age at BCIS diagnosis, lower levels of education, nulliparity, higher Charlson Comorbidity Index, and being hospitalized before BCIS diagnosis; whereas, lower risk of death from breast cancer was seen among BCIS diagnosed in the later time period and those with younger age at first birth. We conclude that most women diagnosed with BCIS die from causes other than breast cancer, which highlights the need for actions not only to reduce nonbreast cancer mortality but also to identify patient where extensive curative BCIS treatment is not adding to survival.     

Twenty‐years experience with de novo metastatic breast cancer

Although new treatments have been widely studied to improve the survival of patients with metastatic breast cancer (BC), prognosis continues to be poor with an average survival time no longer than 3 years. We carried on a population‐based study with the purpose of evaluating the outcome of metastatic breast cancer in the province of Modena from 1990 to 2009. We examined the Modena Cancer Registry and evaluated the 5‐year overall survival (OS) of women diagnosed with a de novo metastatic breast cancer between 1990 and 2009, defining 5 periods of 4 years each. After a median follow‐up time of 29 months, the 5‐year OS was 11% for years 1990–1993, 15% for years 1994–1997, 12% for years 1998–2001, 20% for years 2002–2005 and 29% for years 2006–2009 (p = 0.012). Overall, although no OS differences were noted in the first decade analyzed, a real advantage has been shown in the last two cohorts. In a multivariate analysis, the 5‐year OS was significantly increased only for hormone receptor positive and HER2+ tumors, whereas chemotherapy treatments were not significant independent predictors of survival in “de novo” metastatic BC (p = 0.08). Our analysis confirms that the prognosis of de novo metastatic breast cancer has improved overtime, particularly in the last decade. Trastuzumab, LH‐RH analogues and aromatase inhibitors have determined a significant clinical benefit and cost‐effectiveness in metastatic breast cancer treatment.     

Associations of insulin‐like growth factor and insulin‐like growth factor binding protein‐3 with mortality in women with breast cancer

Elevated circulating insulin‐like growth factor‐1 (IGF‐1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF‐1 are controlled via binding proteins, including IGF Binding Protein‐3 (IGFBP‐3), that may modulate the association of IGF‐1 with breast‐cancer outcomes. We measured IGF‐1 and IGFBP‐3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I‐IIIA breast cancer. We evaluated the association between IGF‐1 and IGFBP‐3, and as a ratio, modeled using quintile cut‐points, with risk of breast cancer‐specific (n = 42 deaths) and all‐cause mortality (n = 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP‐3, women in the highest quintile of IGF‐1 level had an increased risk of all‐cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21–7.93, p = 0.02), although no dose‐response association was evident. The IGF‐1/IGFBP‐3 ratio, an indicator of free IGF‐I levels, was significantly associated with increasing risk of all‐cause mortality (HR = 2.83, 95% CI 1.25–6.36 p_trend = 0.01, upper vs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF‐1 and the IGF‐1/IGFBP‐3 ratio were associated with increased risk of all‐cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.     

Selenium and breast cancer risk: A prospective nested case–control study on serum selenium levels,smoking habits and overweight

Previous research has not been conclusive regarding the association between selenium (Se) and breast cancer. This study was conducted to clarify if there is an association between prediagnostic serum Se levels and breast cancer risk. A population based cohort, the Malmö Diet and Cancer Study, was used and linked with the Swedish cancer registry up to 31 December 2013. Our study included 1,186 women with breast cancer and an equal number of controls. Selenium levels were analysed from stored serum samples. The included individuals were divided into quartiles based on Se value and we compared breast cancer cases with controls using logistic regression yielding odds ratios (OR) with 95% confidence intervals. Serum Se was also analysed as a continuous variable regarding breast cancer risk. The analyses were adjusted for established risk factors and stratified on smoking status and body mass index (BMI). When comparing the highest Se quartile with the lowest, the adjusted OR for breast cancer was 0.98 (0.75–1.26). With selenium as a continuous variable the adjusted OR was 1.00 (1.00–1.01) per 10 ng/ml. When comparing the highest with the lowest Se quartile in women with BMI > 25 kg/m² the adjusted OR was 0.77 (0.53–1.14). We conclude that it is unlikely that prediagnostic serum selenium is overall associated with breast cancer risk and no modifying effect from BMI or smoking was seen.