Hormone replacement therapy and risk of non-hodgkin lymphoma and chronic lymphocytic leukemia.

Our objective in this study was to evaluate whether the use of hormone replacement therapy (HRT) is associated with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). A cohort of 37,220 Iowa women ages 55 to 69 years in 1986 with no history of prior cancer was linked annually to a population-based cancer registry. Through 1998 (13 years of follow-up), 258 incident cases of NHL were identified, including 135 cases of diffuse NHL, 58 cases of follicular NHL, and 31 cases of small lymphocytic NHL. In addition, 63 cases of CLL were identified. Current and former use of HRT (primarily estrogen) and other cancer risk factors were self-reported on the baseline (1986) questionnaire. Compared with never users of HRT at study baseline, current [multivariate relative risk (RR), 1.4; 95% confidence intervals (CIs), 0.9-2.0) but not former (RR, 1.1; 95% CI, 0.8-1.4) users were at increased risk of NHL after adjustment for age and other confounding factors. This association was seen only in nodal NHL [RR(current), 1.5 (95% CI, 1.0-2.4); RR(former), 1.1 (95% CI, 0.8-1.6)] and was not apparent for extra-nodal sites. Of the common subtypes, there was a strong positive association with follicular NHL [RR(current), 3.3 (95% CI, 1.6-6.9); RR(former), 2.6 (95% CI, 1.4-4.7)], and women who were current users for more than 5 years had the highest risk (RR, 3.9; 95% CI, 1.8-8.6). There was no association with diffuse or small lymphocytic NHL, or with CLL. Most of the follicular NHLs were nodal (88%), and exclusion of extra-nodal sites slightly strengthened the association with HRT. For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL.     

Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases were ascertained using nationwide registries. The follow-up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow-up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16-3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96-3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74-10.51) compared to the never use of HRT. In current users of combined HRT with testosterone-like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56-6.75, and RR = 1.94, 95% CI = 1.26-3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin.     

Type of postmenopausal hormone use and risk of breast cancer: 12-year follow-up from the Nurses' Health Study

We prospectively examined the use of hormone replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 12 years of follow-up (480,665 person-years) among postmenopausal women, 1,050 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk. After adjustment for established risk factors, type of menopause, age at menopause, and current age, the rate ratio (RR) was 0.91, 95 percent confidence interval (CI) = 0.78–1.07. the risk of breast cancer was elevated significantly among current users (RR = 1.33, CI = 1.12–1.57); after adjusting for age, we observed no evidence of increasing risk with increasing duration of use among current users (P trend = 0.41), or among past users (P trend = 0.46). Women currently using unopposed estrogen (RR = 1.42, CI = 1.19–1.70), estrogen and progesterone (RR = 1.54, CI = 0.99–2.39), or progesterone alone (RR = 2.52, CI = 0.66–9.63), were all at increased risk of breast cancer compared with never users. These data suggest that long-term past use of estrogen replacement therapy is not related to risk, that current estrogen use increases risk of breast cancer to a modest degree, and that the addition of progesterone does not remove the increased risk observed with current use of unopposed estrogen.The authors are with the Nurses' Health Study, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and Harvard Medical School, Boston, MA, USA. Address correspondence to Dr Colditz, Channing Laboratory, 180 Longwood Ave., Boston, MA 02115-5899, USA. Supported by research grant CA40356 from the National Cancer Institute, NIH, Department of Health and Human Services. Dr Colditz is supported by an American Cancer Society Faculty Research Award FRA-398.     

Hormone replacement therapy and breast cancer in former users of oral contraceptives--The Norwegian Women and Cancer study

Combined estrogen-progestin menopausal therapy (HRT) and combined estrogen-progestin contraceptives (OC) both increase breast cancer risk during current use and a few years after. We investigated risk of breast cancer in women who were users of HRT dependant on former history of OC use in a large, national population-based cohort study, the Norwegian Women and Cancer study (NOWAC). Exposure information was collected through postal questionnaires. Based on follow-up of 30,118 postmenopausal women by linkage to national registers of cancer, deaths, and emigration we revealed 540 incident breast cancer cases between 1996 and 2004. Compared to never users of either drugs current use of HRT gave a significant (p = 0.002) higher risk of breast cancer in former OC users, RR = 2.45 (95% CI 1.92-3.12), than among never users of OCs, RR = 1.67 (1.32-2.12). Relative risk of current use of HRT was similar for estrogen only and combinations with progestin added in ever users of OCs. The increased risk of breast cancer in current HRT users with a history of former OC use could have potential great impact on postmenopausal breast cancer risk as the proportion of postmenopausal women with former OC use will continue to increase.     

Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States)

Objective: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Methods: Using data from an incident population-based case (n = 1972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Results: Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23–1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24–2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29–2.12). BMI (kg/m²) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51–4.13; premenopausal, OR 2.19, 95% CI 0.94–5.07; postmenopausal using HRT, OR 3.36, 95% CI 1.58–7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. Conclusions: These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age.     

Estrogen and estrogen-progestin replacement therapy and risk of postmenopausal breast cancer in Canada

Objective: To examine the association between hormone replacement therapy (HRT) use and breast cancer incidence and to determine whether the association differs according to type of regimen. Method: Data were collected in Ontario from 404 incident cases and 403 age frequency-matched controls, between 1995 and 1996, using a self-administered questionnaire. Results: Multivariate analyses revealed an elevated odds ratio among long-term (ten years) HRT users (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.06–3.06). Risk among long-term estrogen–progestin users was substantially higher (OR = 3.48, 95% CI 1.00–12.11) than risk among long-term users of estrogen alone (OR = 1.74, 95% CI 0.93–3.24). Among both estrogen and estrogen–progestin users, positive associations were not observed for durations of use less than ten years. Conclusion: These data suggest that long-term use of HRT increases the risk of breast cancer and that estrogen–progestin therapy may be more detrimental than estrogen use alone.     

A prospective study of different types of hormone replacement therapy use and the risk of subsequent breast cancer: the women's health in the Lund area (WHILA) study (Sweden)

Objectives: Reports suggest that combined estrogen plus progestin hormone replacement therapy (HRT) confers a higher breast cancer risk than estrogen alone. We aimed to establish whether breast cancer risk depends on the type of HRT formula. Methods: The cohort consisted of 6586 women, aged 50–64 years, from the Lund area, Sweden, with no reported breast cancer upon inclusion. We obtained information such as HRT use through a questionnaire between December 1995 and February 2000. New breast cancers were identified through the South Swedish tumor registry. Results: Between inclusion and December 2001, 101 women developed breast cancer. Only ever use of the continuous combined estrogen plus progestin (CCEP) formula differed between cases and controls (45.2% versus 23.5%; p = 0.000001). Compared with never users, exclusive CCEP users had the highest age-adjusted hazard ratio HR 3.3 (95% CI: 1.9–5.6; p < 0.001), followed by users of CCEP in addition to other HRT formulas HR 2.8 (95% CI: 1.4–5.5; p = 0.003). No significant increase was seen in women who exclusively used other HRT formulas. Conclusion: Women who used CCEP had over three times the risk of developing breast cancer compared with never users and twice the risk compared with users of other types of HRT.     

Risks of breast and endometrial cancer after estrogen and estrogen–progestin replacement

Objective: We studied the risk of breast and endometrial cancer in a cohort of 11,231 Swedish women prescribed different replacement hormone regimens.Methods: All 10,472 women at risk of developing breast cancer and 8,438 women at risk of endometrial cancer were followed up from the time of the questionnaire in 1987–88 through 1993, by record-linkages to the National Swedish Cancer Registry. Using data from a questionnaire we analyzed the relationships between hormone exposures and cancer risk, with non-compliers and users of less than 1 year as a reference group.Results: For breast cancer, women reporting use of estrogens combined with progestins had evidence of an increased risk relative to women denying intake or taking hormones for less than 1 year; relative risk (RR) = 1.4 (95% confidence interval 0.9–2.3) after 1–6 years of intake, and RR=1.7 (95% CI 1.1–2.6) after more than 6 years. This excess risk seemed confined to recent exposure. We found no association with intake of estrogens alone using non-compliers and short-term takers as the reference group. The risk of invasive endometrial cancer was increased four-fold in women using medium-potency estrogens alone for 6 years or longer, RR = 4.2 (95% CI 2.5–8.4). Women on such long-term progestin-combined treatment had a lower, non-significant, excess risk (RR = 1.4; 95% CI 0.6–3.3).Conclusions: We conclude that long-term recent use of estrogen–progestin combined replacement therapy may increase the risk of breast cancer. Exposure to estrogen alone substantially elevates the risk of endometrial cancer, an increase that can be reduced or perhaps avoided by adding progestins.     

Exogenous hormone use and the risk of postmenopausal breast cancer: results from the Netherlands Cohort Study

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]=0.79–1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5–9 years, 10–14 years, and 15+ years were 0.97 (0.61–1.55), 1.20 (0.69–2.07), 1.03 (0.60–1.77), and 1.96 (0.99–3.89), respectively. The test for trend was not significant (P=0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI=0.67–3.41), whereas in the remaining women, the RR was 0.97 (CI=0.73–1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR=0.99, CI=0.68–1.43). Also, the number of years of HRT use was not associated with an increased breast cancer risk (trend P=0.83), nor was the number of years between the first and the last use of HRT and breast cancer incidence. One subgroup of women in which the use of HRT seemed associated (but not significantly) with an increase in breast cancer risk was women with an induced menopause (RR=1.72, CI=0.95–3.12). The RR of breast cancer for women who had ever used both OCs and HRT, compared with women who never used these exogenous hormones was 1.00 (CI=0.51–1.94). From this study, it cannot be concluded that the use of exogenous hormones is a strong risk factor for the development of postmenopausal breast cancer.Since the acceptance of this paper, two other papers have been published on HRT and breast cancer. For HRT (estrogen alone), one supports our finding of no association (Stanford et al, JAMA 1995; 274: 137–42) and one did find a positive association for current use (Colditz et al, New Engl J Med 1995; 332: 1589–93), most pronounced in older women with longer durations of use. With regard to use of combined estrogen-progestin HRT, the results in both papers were comparable to those for estrogen alone. More research on (combinations of) types of hormones is needed.This work was supported by the Dutch Cancer Society.     

Increased incidence of small and well-differentiated breast tumours in post-menopausal women following hormone-replacement therapy

Exposure to hormone-replacement therapy (HRT) has consistently been associated with an increased incidence of breast cancer, particularly of small tumours. Other tumour characteristics in relation to HRT have received less scientific attention. Our aim in this population-based prospective cohort study was to assess whether HRT is associated with an increased incidence of breast-cancer subgroups defined in terms of stage, type (according to the WHO system), Nottingham grade and the Nottingham Prognostic Index (NPI). Evaluation was based on a cohort of 5,865 post-menopausal women followed for an average of 9.8 years. Twenty percent of women reported current use of HRT at the time of the baseline interview. Record linkage with the Swedish Cancer Registry and local clinical registries identified 141 incident invasive breast-cancer cases. All tumours were reclassified by 1 pathologist. The incidence of breast cancer in HRT users was 377/10(5) and in non-users 221/10(5) person-years [relative risk (RR) = 1.72, 95% confidence interval (CI) 1.17-2.52]. This risk remained statistically significant after adjustment for established risk factors in a Cox proportional hazards analysis (RR = 1.66, 95% CI 1.12-2.45). Among HRT users, there was over-representation of cases with stage I tumours (adjusted RR = 2.33, 95% CI 1.44-3.76), of lobular carcinomas (RR = 4.38, 95% CI 1.60-12.0) and of tubular tumours (RR = 4.81, 95% CI 1.37-16.8). Nottingham grade I/II carcinomas (RR = 2.02, 95% CI 1.29-3.16) and cases with NPI < or = 3.4 (RR = 2.29, 95% CI 1.41-3.72) were similarly over-represented among HRT users. Incidence of breast cancer was increased in post-menopausal women who used HRT at baseline. Among HRT users, there was over-representation of tumours that, with regard to stage, type and grade, are associated with a favourable prognosis.     

Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States

This study examines the relationship between fatal breast cancer and use of estrogen replacement therapy (ERT) among women in a large prospective study in the United States. After nine years of follow-up, 1,469 breast cancer deaths were observedin a cohort of 422,373 postmenopausal women who were cancer free at study entry and who supplied information on estrogen use. Results from Cox proportional hazards modeling, adjusted for 11 other potential risk factors, showed that ever-use of ERT was associated with a significantly decreased risk of fatal breast cancer (rate ratio [RR]=0.84,95 percent confidence interval [CI]=0.75–0.94). There was a moderate trend (P=0.07) of decreasing risk with younger age at first use of ERT. This decreased risk was most pronounced in women who experienced natural menopause before the age of 40 years (RR=0.59, CI=0.40–0.87). There was no discernible trend of increasing risk with duration of use in estrogen users at baseline or former users, nor was there any trend in years since last use in former users. The relationship between ERT and breast cancer mortality differed by age at menarche and by a self-reported history of breast cysts. No increased risk of fatal breast cancer with ERT was observed with estrogen use status (baseline/former), age at first use, duration of use, or years since last use. These findings suggest that ever-use of ERT is associated with a 16 percent decreased risk of fatal breast cancer.     

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.     

Hormone Replacement Therapy,Reproductive History,and Colorectal Adenomas: Data from the Prostate,Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (United States)

Objective Findings from some epidemiologic studies of colorectal cancer and adenoma suggest that the protective effect of post-menopausal hormone replacement therapy (HRT) may differ across categories of age and body mass index (BMI). We conducted an analysis of women participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to investigate the relationship between HRT use and prevalent adenoma, both overall and across different population subgroups.Methods Women aged 55–74 were randomized to screening by flexible sigmoidoscopy at ten PLCO screening centers between September 1993 and September 2001. We identified 1468 women with at least one left-sided adenoma and 19,203 without adenoma or colorectal cancer. Information about HRT and reproductive factors was obtained from a self-administered questionnaire.Results Compared to never use of HRT, current use was associated with a decreased prevalence of left-sided adenoma (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.75–0.97). We found no evidence of dose–response with increasing duration of use for current or former users. The association with current HRT use was stronger among women aged 65+ (OR 0.69; 95% CI 0.56–0.84), with a BMI<30 (OR 0.82; 95% CI 0.71–0.95) and who regularly use aspirin or ibuprofen (OR 0.77; 95% CI 0.65–0.91). Other reproductive factors were not significantly associated with adenoma prevalence.Conclusions Our findings suggest that current HRT use may protect against colorectal adenoma, and that this protective effect is short-lived following cessation of use.     

Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women.

BACKGROUND: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. METHODS: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin <15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% CI, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated > or =10 years after last use (RR, 1.5; 95% CI, 1.0-2.1). CONCLUSIONS: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research.     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO)

Background:

The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated.

Methods:

We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types.

Results:

A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed.

Conclusion:

Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.     

Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study

Increasing use of HRT over the last 2 decades could have contributed to the increasing incidence of cancer in women. Our aim was to investigate the relation between use of HRT and risk of hormone-dependent cancers in a Norwegian cohort of women. The Norwegian Women and Cancer (NOWAC) study is a representative, national, population-based cohort study. This report includes 35,456 postmenopausal women aged 45-64 years who answered a postal questionnaire in 1996-1998 providing information on reproduction, lifestyle and use of HRT. The women were followed up for cancer incidence. The main analyses were restricted to 31,451 postmenopausal women with complete information. Ever use of HRT was reported by 43.5% and current use, by 35% of the women. Current users had an increased risk of breast cancer (adjusted RR=2.1, 95% CI 1.5-2.5). The risk increased with increasing duration of use (ptrend < 0.0001). Using a regimen of continuous estrogen-progestagen implied an increased risk. Adjusted RRs associated with <5 and > or =5 years' duration of use were 2.6 (95% CI 1.9-3.7) and 3.2 (95% CI 2.2-4.6), respectively. The population-attributable risk of breast cancer due to current use of HRT was 27%. We found no significant increase in risk of ovarian cancer. Neither did we find users of estrogen-progestagen preparations to have any increase in risk of endometrial cancer. Our results suggest that HRT could be considered a major determinant for the increasing incidence of breast cancer in Norway.     

A prospective study of lifestyle factors and the risk of pancreatic cancer in Nord-Trøndelag, Norway

Objectives: Cancer of the pancreas is highly fatal and, despite extensive scrutiny, only cigarette smoking stands out as a likely causal agent in epidemiological studies. To explore to what extent different lifestyle factors are associated with the risk of pancreatic cancer, data from a large health screening survey in a county in Norway were analyzed. Methods: Our study included 31,000 men and 32,374 women initially free from any diagnosed cancer, and during 12 years of follow-up, 166 incident cases of pancreatic cancer were diagnosed at the Cancer Registry. Results: Compared with never smokers, we found a two-fold increased risk among current smokers, and a dose–response association with number of cigarettes (p for trend = 0.02 for both men and women) and with number of pack-years (p for trend = 0.02 for men and 0.01 for women). The risk among former smokers quitting more than 5 years before study entry was close to the risk of never smokers. Compared with persons who reported never or infrequently to be physically worn out after a day's work, the relative risk (RR) among those who nearly always became worn out was 2.9 (95% confidence interval (CI) = 1.4–5.8) for men and 3.8 (95% CI = 1.6–9.2) for women. Divorced or separated men had a risk of 3.1 (95% CI = 1.3–7.2) compared with married men. We observed a higher risk among women in occupations of high socioeconomic status (RR = 2.5; 95% CI = 1.2–5.2), and among men occupied in farming, agriculture or forestry (RR = 2.1; 95% CI = 1.1–4.0), compared with persons in occupations of low socioeconomic status. Conclusions: Our results confirm the findings of previous studies that indicate a causal role of cigarette smoking in pancreatic cancer. Moreover, we found that the risk of former smokers may approach the risk of never smokers within a few years subsequent to quitting.     

Estrogen-progestin replacement therapy and breast cancer risk: the Women's Health Study (United States)

Objective: While there is substantial evidence that unopposed estrogen use increases the risk of breast cancer, there are limited data from epidemiologic studies on the impact of estrogen–progestin combinations. We therefore examined estrogen–progestin replacement therapy and breast cancer risk in the Women's Health Study. Methods: We investigated postmenopausal hormone (PMH) use among 17,835 apparently healthy postmenopausal women aged 45 years, and followed them prospectively for an average of 5.9 years. Breast cancer occurred in 411 women. Results: The multivariate relative risks of all breast cancer associated with never use of PMH, use of estrogen replacement therapy (ERT), and use of estrogen–progestin replacement therapy (HRT) were 1.00 (referent), 0.96 (95% CI 0.65–1.42), and 1.37 (95% CI 1.05–1.78). The increase in risk among users of HRT was largely limited to those women who had used estrogen–progestin replacement therapy for five years or more, and to those women who were on continuous rather than cyclic progestin combinations. Higher doses of estrogen, but not progestin, were associated with increased breast cancer risk, compared with lower doses. Conclusions: These prospective data suggest that use of estrogen–progestin replacement therapy imparts an increased risk of breast cancer in comparison with never use of PMH.     

A prospective study of postmenopausal hormone use and ovarian cancer risk

The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk is unclear, particularly for specific hormone formulations, but recent studies suggest that there is a positive association. We conducted a prospective observational study with 82,905 postmenopausal women, including 389 ovarian cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users of PMH, both current and past users of > or =5 years had a significantly elevated risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone type in continuous years, use of unopposed estrogen was associated with a significant increase in the risk of epithelial ovarian cancer (P for trend <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not significantly associated with ovarian cancer risk. Generally, results were similar for serous tumours (RR for 5-year increment of unopposed estrogen use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency of use was not significantly associated with ovarian cancer risk, but statistical power was limited here.