Occupational physical activity and risk of cancer of the colon and rectum in New Zealand males

The association between occupational physical activity and risk of colorectal cancer by age and anatomic site was investigated in a study of 2,503 males with colorectal cancer registered with the New Zealand Cancer Registry during 1972–80. Occupational groups that involved high levels of physical activity or were predominantly sedentary were identified prior to analysis of the registry data. Relative to males in high physical activity occupations, males in sedentary occupations had an increased incidence of both cancer of the colon (relative risk [RR]=1.2; 95 percent confidence interval [CI]=1.0–1.4) and rectum (RR=1.3, CI=1.0–1.5). The RRs for sedentary workers were particularly elevated in the 35–44 and 45–54 year age-groups for colon cancer (RR=1.8 and 1.5, respectively) and in the 45–54 year age-group for rectal cancer (RR=1.5), whereas there was no increase in risk for sedentary workers in the 55–64 year age-group for either cancer site. The generalincrease in colon cancer incidence for New Zealand during the study period was reflected in the sedentary group, but there was no change in incidence among men in occupations involving high or intermediate levels of physical activity. There was no obvious pattern for the increased cancer risk for men in sedentary occupations by anatomic site. Current physiologic hypotheses for the effect of physical activity on colon cancer risk do not adequately explain an association of physical activity with risk of rectal cancer.Dr Fraser is affillated with the University of Otago, Medical School, Dunedin, New Zealand. Dr Pearce is with the Wellington School of Medicine, Wellington, New Zealand. Address correspondence to Dr Fraser, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin, New Zealand.     

Oral contraceptive use and risk of breast cancer in older women (New Zealand)

the effect of oral contraceptive (OC) use at older ages on the risk of breast cancer was examined in a national population-based case-control study conducted in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer, and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. The relative risk (RR) of breast cancer for women aged 45 to 54 years at diagnosis who had ever used OCs was 1.0 (95 percent confidence interval [CI]=0.77–1.3). There was no significant increase in risk of breast cancer among recent users of OCs of any age. Analyses according to age at first and last use among women aged 40 years and older at diagnosis showed no group with an elevated risk of breast cancer. Women who had used OCs for 10 years or longer after age 40 had an apparent increase in risk (RR=2.7, CI=0.97–7.5), but the trend in risk with duration of use was not significant. These findings suggest that OC use in older women does not affect their risk of breast cancer appreciably, but it is not possible to rule out a modest increase in risk with such use.This research was supported by grants from the Medical Research Council of New Zealand and from the Special Programme of Research, Development, and Research Training in Human Reproduction, World Health Organization.     

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.     

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n=6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n=9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR]=1.1, 95 percent confidence interval [CI]=10–1.2). Total duration of usealso was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI=0.9–1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR=2.0, CI=1.1–3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m²) less than 20.4, RR=1.7, CI=1.1–2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.Authors are with the University of Wisconsin Comprehensive Cancer Center, Madison, WI, USA (Dr Newcomb, Ms Trentham Dietz); NIEHS Epidemiology Branch, Research Triangle Park, NC (Dr Longnecker); Fred Hutchinson Cancer Research Center, Seattle, WA (Dr Surer); Department of Obstetrics and Gynecology, Pritzker School of Medicine, The University of Chicago, Chicago, IL (Dr Mittendorf); Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH (Dr Baron); Boston University, School of Public Health, Boston, MA (Dr Clapp); Department of Epidemiology and Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women's Hospital, Boston, MA (Dr Willett). Address correspondence to: Dr Polly A. Newcomb, University of Wisconsin-Madison Comprehensive Cancer Center, 1300 University Ave., #4780, Madison, WI 53706, USA. Supported by Public Health Service (National Cancer Institute) grants R01 CA 47147 and R01 CA 47305.     

Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of United States women

Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer. Thus, the association of fatal breast cancer and spontaneous abortion was examined in a large prospective study of United States adult women. After seven years of follow-up, 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories. Results from Cox proportional hazards models, adjusted for other risk factors, showed no association between a history of spontaneous abortion and risk of fatal breast cancer (rate ratio [RR]=0.89, 95 percent confidence interval [CI]=0.78–1.02). The RR did not increase with increasing numbers of abortions. Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion (RR=0.76, CI=0.54–1.05). Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant (RR=0.61, CI=0.27–1.38) or whose only pregnancy ended in a livebirth (RR=0.72, CI=0.32–1.65). These findings do not support an association between spontaneous abortion and fatal breast cancer.     

A prospective study of cigarette tar yield and lung cancer

We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30–89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR]=1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI]=0.98–1.05; RR=0.99, CI=0.96–1.03 in women). However, in long-term (>20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR=0.36, CI=0.18–0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR=1.04, CI=0.58–1.87).Authors are with the Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611, USA. Address correspondence to Dr Sidney. This study was funded by grants R01 CA 36074 and R35 CA 49761 from the US National Cancer Institute.     

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.     

Reproductive factors,exogenous female hormones,and colorectal cancer by subsite

The associations between reproductive factors, exogenous hormones, and colorectal cancer were examined among female subjects in a population-based case-control study in Sweden. The study was performed in Stockholm in 1986–88, and included 299 cases and 276 controls. There was little evidence that age at first birth, number of months of breast feeding, age at menarche, or age at menopause influenced the risk of colon or rectal cancer. However, the results indicate that postmenopausal hormone-replacement therapy might reduce the risk of colorectal cancer (age-adjusted relative risk [RR]=0.4, 95 percent confidence interval [CI]=0.2–0.9). Compared with nulliparous women, women with at least four births were at reduced risk for colon cancer (RR=0.5, CI=0.2–1.2) but not rectal cancer (RR=1.0, CI=0.4–2.6). However, no trend across increasing parity was observed. Adjustments for diet, body mass, and physical activity had little influence on the results.The authors are with the Department of Preventive Medicine, University of Southern California School of Medicine. Dr Gerhardsson de Verdier is also in the Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. Address correspondence to Dr London, University of Southern California School of Medicine, Department of Preventive Medicine, PMB B306, 1420 San Pablo Street, Los Angeles, CA 90033, USA. The study was supported by two grants (2228-B86-013XA; 2228-B87-02XA) from the Swedish National Cancer Society.     

Second primary cancers following cancers of the kidney and prostate in New South Wales (Australia), 1972–91

Data from the New South Wales (NSW) (Australia) Central Cancer Registry for the period 1972–91 were examined to determine the risk of second primary cancers following an initial invasive cancer of the renal parenchyma (ICD-9 code 189.0), renal pelvis (code 189.1), or prostate (code 185). Eligible cases were restricted to those who had survived for at least two months after diagnosis of the first primary cancer. Expected numbers of cancers were obtained by assuming that subjects experienced the same cancer incidence as prevailed in the corresponding general population and applying gender-, age-, and calendar-specific rates to the appropriate person-years at risk. The relative risk (RR) of a second primary cancer was taken to be the ratio of observed to expected numbers of second cancers. Following prostatic cancer, there was an overall deficit of cancers at all sites combined (RR=0.79, 95 percent confidence interval [CI]=0.75–0.84), and no site had a significantly raised RR. Taking this into consideration, there appeared to be a reciprocal relationship of increased risk of prostatic cancer (RR=1.7, CI=1.2–2.3) following an initial cancer of the renal parenchyma and of renal parenchymal cancer (RR=1.2, CI=0.8–1.7) after cancer of the prostate. An increased risk of bladder cancer occurred following renal parenchymal (RR=3.4, CI=1.1–8.0, for women only) as well as after renal pelvic cancer (men:RR=8.7, CI=5.4–13; women:RR=39, CI=26–56). A tobacco-related pattern of excess risk was seen after renal pelvic cancer but not after cancer of the renal parenchyma. These data illustrate that an excess of second primary cancers may reflect shared etiologic factors or increased medical surveillance.Dr McCredie and Ms Coates are with the New South Wales Cancer Council in the Cancer Epidemiology Research Unit (Dr McCredie) and NSW Central Cancer Registry (Ms Coates). Dr Stewart is with the Western Clinical School, University of Sydney, Australia. Dr Macfarlane is with the ARC Epidemiology Unit, University of Manchester, UK. Address correspondence to Dr McCredie, Cancer Epidemiology Research Unit, NSW Cancer Council, PO Box 572, Kings Cross 2011, New South Wales, Australia.     

Strenuous physical activity in young adulthood and risk of breast cancer (United States)

The epidemiologic data on the relation between strenuous physical activity and breast cancer are limited and inconsistent. Because risk of breast cancer may be influenced by ovarian function which, in turn, is modulated by physical activity, the hypothesis that exercise may be associated with a reduced risk of breast cancer merits further investigation. We, therefore, conducted a large case-control study in 1988–91, and interviewed 6,888 women (17 to 74 years of age) with breast cancer in Maine, Massachusetts, New Hampshire, and Wisconsin (United States). Interviewed controls (9,539 women, 18 to 74 years of age) were selected randomly from lists of licensed drivers (for younger women) or from a roster of Medicare enrollees (for older women). We used multivariate adjusted odds ratios (OR) and 95 percent confidence intervals (CI) from logistic regression models to estimate relative risks between self-reported physical activity when 14 to 22 years of age and breast cancer. When compared with sedentary controls, women who reported any strenuous physical activity during ages 14 to 22 years had a modest reduction in the risk of breast cancer (OR=0.95, CI=0.93–0.97). However, those who exercised vigorously at least once a day had a 50 percent reduction in risk of breast cancer (OR=0.5, CI=0.4–0.7). These data support the hypothesis that women who are physically active have a reduced risk of breast cancer.This project is funded by grants (R01 CA 47147 and R01 CA 47305) from the US Public Health Service.Dr Mittendorf was also supported by National Research Service Award No. 5 T32 ES07069.     

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.     

Oral contraceptive use and breast cancer risk among African-American women

Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI=1.5–5.0) for three to four years of use, and declined to 1.5 (CI=0.8.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI=0.7–2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.This research was supported by the US National Cancer Institute (grants R01 CA55766 and R01 CA45762). Additional support was provided by the US Food and Drug Administration (FD-U-000082); the views expressed do not necessarily represent the views of the Food and Drug Administration. The Slone Epidemiology Unit also receives support from Hoffmann-La Roche, Inc., and Marion Merrell Dow Inc.     

Parental ages at birth in relation to a daughter's risk of breast cancer among female participants in the Framingham study (United States)

Data from the Framingham Heart Study, collected in Framingham, MA (United States) during 1948–86, were used to evaluate the relation of parental age at birth to the risk of breast cancer among daughters. After 38 years of follow-up, 149 breast cancer cases occurred among 2,662 women. All but two cases were confirmed by histologic report. The rate of breast cancer increased among daughters with increasing maternal age at birth up to the mid-30s, where the rate levelled off. A similar pattern was observed with paternal age. After adjustment for other confouding factors and paternal age, the rate ratios for breast cancer in daughters whose mothers were aged 26 to 31 years and 32 or more years at their birth, relative to women whose mothers were aged 25 years or younger, were 1.5 (95 percent confidence interval [CI]=1.0–2.4) and 1.3 (CI=0.8–2.2), respectively. However, there was no longer an association between paternal age at birth and risk of breast cancer after controlling for maternal age and other risk factors.Drs Zhang, Cupples, and Coulton are with the Department of Epidemiology and Biostatistics, School of Public Health, Boston University, Boston, MA, USA, Dr Rosenberg is with the Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA. Dr Kreger is with the Section of Preventive Medicine and Epidemiology, The Evans Memorial Department of Clinical Research, Boston University Medical Center, Boston, MA. Address correspondence to Dr Zhang, Department of Epidemiology and Biostatistics, School of Public Health, Boston University, 80 East Concord Street, Boston, MA, 02118-2394, USA.     

Tubal sterilization and risk of breast cancer mortality in US women

Objective: To investigate the hypothesis that tubal sterilization is associated with a reduced risk of breast cancer. Methods: We examined this hypothesis in a large prospective study of US adults. After 14 years of mortality follow-up, 3837 deaths from breast cancer were observed in a cohort of 619,199 women who were cancer-free at study entry in 1982. Results: Cox proportional hazards models (adjusted for multiple breast cancer risk factors) showed a significant inverse association between tubal sterilization and breast cancer mortality (adjusted rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70–0.96). Women who were sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53–0.88) than women who were sterilized at 35 years of age or older (adjusted RR = 0.92, 95% CI 0.75–1.13). Also, sterilizations performed before 1975 resulted in a lower risk (RR = 0.75, 95% CI 0.62–0.91) than those performed during or after 1975 (RR = 0.98, 95% CI 0.74–1.29), possibly reflecting the likelihood of greater tissue damage with earlier procedures. Conclusions: These results suggest that tubal sterilization may lower subsequent risk of breast cancer, especially among women who are sterilized at a relatively young age. Additional studies are needed to confirm or refute these findings.     

Breast cancers among very young premenopausal women (United States)

Objective: To assess risk factors for breast cancer among very young compared to older premenopausal women. Methods: Between 1990 and 1992 a population-based case–control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20–54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. Results: Among the youngest age group (<35 years, n = 545), significant predictors of risk included African-American race (RR = 2.66; 95% CI 1.4–4.9) and recent use of oral contraceptives (RR = 2.26; 95% CI 1.4–3.6). Although these relationships were strongest for estrogen receptor-negative (ER–) tumors (RRs of 3.30 for race and 3.56 for recent oral contraceptive use), these associations were also apparent for young women with ER+ tumors. Delayed childbearing was a risk factor for ER+ tumors among the older premenopausal women (p _trend < 0.01), but not for women <35 years in whom early childbearing was associated with an increased risk, reflecting a short-term increase in risk immediately following a birth. Family history of early-onset breast cancer was more strongly associated with risk among women <35 years (RR = 3.22) than those 45–54 years (RR = 1.51). Risk factors for premenopausal breast cancer not significantly modified by age at diagnosis included early age at menarche, low body mass index, and heavy alcohol consumption. Conclusion: These findings suggest the possibility that women who develop breast cancers at very young ages may be etiologically as well as clinically distinct.     

Diet in adolescence and the risk of breast cancer: results of the Netherlands Cohort Study

Objectives: In The Netherlands, part of the population experienced food restriction and severe famine during World War II. The purpose of this study was to study the effects of severe undernutrition during adolescence on the risk of breast cancer later in life.Methods: We examined the hypothesis in the Netherlands Cohort Study on diet and cancer (NLCS), among 62,573 women aged 55–69 years. Baseline information on diet and other risk factors was collected with a questionnaire in 1986. Information was collected on residence in the Hunger winter (1944–1945) and War years (1940–1944) and fathers' employment status in 1932–1940 as indicators of exposure. After 6.3 years of follow-up, 1009 incident breast cases were available for analysis.Results: In multivariate case-cohort analysis, residents of the western part of the country in 1944–1945 had an increased breast cancer risk (western city RR=1.1, 95% CI: 0.9–1.4, western rural area RR = 1.5, 95% CI: 1.1–1.9). For the War years (1940–1944) we found no association between breast cancer risk and urban vs. rural residence. Women whose fathers were unemployed during the Depression years (1932–1940) had a non-significant decrease in breast cancer risk (RR = 0.9, 95% CI: 0.7–1.2). Exposure to energy restriction during the adolescent growth spurt or during the period between menarche and birth of the first child did not change the RRs substantially.Conclusions: We found no clear evidence in this study for the hypothesis that energy restriction in adolescence leads to a decreased breast cancer risk.     

The association of height,weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom)

The association with breast cancer of menstrual and reproductive events, family history of breast cancer, and body size have been studied on two cohorts of 6,706 volunteers on the island of Guernsey (United Kingdom), 168 of whom had breast cancer detected during follow-up. The median follow-up time of the non-cases was 21 years in the first study and 10 years in the second. A time-dependent Cox regression model was fitted to the data with age as the time-dependent variable in order to represent the effect of changing menopausal status. Other variables examined in the model were age at menarche, parity, age at first birth, family history of breast cancer, height, weight (both directly measured), relative weight (weight [kg]/height[m]), and Quetelet's body mass index (weight[kg]/height[m]²). Interactions between age and all other covariates also were examined. Family history was found to be the most important risk factor for women aged less than 51 years (relative risk [RR]=3.5, 95 percent confidence interval [CI]=2.0–6.0), and intervals between menarche and first birth longer than 14 years were found to increase significantly the risk of breast cancer in women older than 61 years (RR=2.4, CI=1.3–4.4). Height was the only indicator of body size which was associated significantly with risk of breast cancer, the estimated regression coefficient indicating an increase in risk of about 70 percent for women on the 90th centile of height relative to those on the 10th centile. A survey of the literature showed that the association between risk of breast cancer and height was found in those studies which used direct measurements of height but not in others which used self-reported values.     

Occupational physical activity and risk for breast cancer in a nationwide cohort study in Sweden

Objective: Our purpose was to investigate effects of physical activity on risk for breast cancer.Methods: From the Swedish nationwide censuses in 1960 and 1970 we defined three partly overlapping cohorts of women whose occupational titles allowed reproducible classification of physical demands at work in 1960 (n=704,904), in 1970 (n=982,270), or with the same demands in both 1960 and 1970 (n=253,336). The incidence of breast cancer during 1971–89 was ascertained through record linkage to the Swedish Cancer Register. We used Poisson regression to estimate relative risks (RR).Results: A total of 20,419, 22,840, and 8261 breast cancers, respectively, were detected in the three cohorts. In all three cohorts the risk for breast cancer increased monotonically with decreasing level of occupational physical activity and with increasing socioeconomic status. Among women with the same estimated physical activity level in 1960 and 1970 the RR was 1.3 for sedentary as compared with high/very high activity level (95% CI 1.2–1.4; p for trend<0.001). Adjustment for socioeconomic status virtually eliminated this association (RR 1.1; 95% CI 0.9–1.2; p for trend 0.12) leaving a statistically significant 30% gradient only among women aged 50–59 years at follow-up. The association between socioeconomic status and breast cancer risk was largely unchanged after adjustment for occupational physical activity.Conclusion: The protective effect of occupational physical activity on breast cancer risk, if any, appears to be confined to certain age groups.     

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.     

Difficulty becoming pregnant and family history as interactive risk factors for postmenopausal breast cancer: the Iowa Women's Health Study

We recently provided data from a prospective cohort study of postmenopausal women which suggested that a first livebirth at age 30 or older (cf before age 20) was associated with a twofold increased risk of breast cancer in women without a family history, but a 5.8-fold higher risk in women with a positive family history. To address the question of whether these observations reflect difficulty becoming pregnant or maintaining a pregnancy, we performed additional analyses in which the outcome of each pregnancy was considered. During five years of follow-up, 620 incident cases of breast cancer were identified in the 37,105 women at risk. There was little evidence for an increased risk associated with a history of spontaneous abortion (relative risk [RR]=1.1; 95 percent confidence interval [CI]=0.9–1.4), nor was the risk higher among women who reported two or more spontaneous abortions in consecutive pregnancies (RR=1.0, CI=0.7–1.4). Although women who reported that they had tried unsuccessfully to become pregnant had only slightly and nonsignificantly elevated risks of breast cancer (RR=1.1, CI=0.9–1.3), a more pronounced and statistically significant association was noted in women with a positive family history (RR=2.0, CI=1.4–3.2). There was a strong inverse association between failure to become pregnant and parity (P<0.0001); nearly 50 percent of the nulliparous married women reported having tried and failed to become pregnant, whereas the frequency was only 6.8 percent among married women with five or more livebirths. Thus, difficulties in becoming pregnant may characterize a subset of women at increased risk of breast cancer, especially in the presence of a family history.The authors are with the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Dr Sellers is also affiliated with the Institute of Human Genetics, University of Minnesota School of Medicine. Address correspondence to Dr Sellers, Division of Epidemiology, Suite 300, 1300 South Second Street, Minneapolis, MN 55454-1015. This publication was supported by a grant (RO1 CA39742) from the US National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.