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.     

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.     

Abortion and breast cancer risk in seven countries

Epidemiologic studies have been inconsistent in suggesting an association between abortion and breast cancer risk. Whether the protection provided by a full-term pregnancy also results from a short-term pregnancy or whether a prematurely terminated pregnancy could increase the risk of breast cancer is unclear. Data from a large, international collaborative study were used to evaluate the association between abortions, whether spontaneous or induced, and breast cancer risk. The data from seven countries included 3,958 breast cancer cases and 11,538 hospital controls with information on abortion history obtained through interviews. Compared with nulliparous women with no abortion (baseline), the odds ratios (OR) and 95 percent confidence intervals (CI) were: for nulliparous women with a history of prior abortion, 0,86 (CI=0.68–1.08); for parous women with no history of abortion, 0.63 (CI=0.57–0.69); for parous women with abortion before first birth, 0.82 (CI=0.69–0.97); and, for parous women with abortion only after first birth, 0.70 (CI=0.63–0.79). When restricting analysis to parous women, those with a history of abortion exhibited an elevated OR suggesting a 29 percent risk increase if the incomplete pregnancy occurred before first birth (CI=1.16–1.36) and an 11 percent risk increase for abortion only after first birth (CI=1.02–1.20) compared with women without such history. The associations observed were stronger among the youngest women. These results do not support a large overall association between abortion and breast cancer risk.Ms Michels and Drs Hsieh, Trichopoulos, and Willett are with the Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. Dr Willett is also affiliated with the Department of Nutrition, Harvard School of Public Health, and Channing Laboratory, Department of Medicine, brigham and Women's Hospital and Harvard Medical School, Boston, MA. Address correspondence to Ms Michels, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.     

Diet,alcohol, and smoking and the occurrence of hyperplastic polyps of the colon and rectum (United States)

Hyperplastic polyps of the colon reveal a geographic distribution similar to that of colorectal cancer and adenomatous polyps. However, unlike adenomas—known precursors of colorectal cancer—little is known about the etiology or clinical significance of the hyperplastic polyp. In this prospective study, we set out to determine the main dietary and other lifestyle factors in the United States that might be associated with this lesion. Hyperplastic polyps of the distal colon and rectum were diagnosed in 219 of 12,922 men of the Health Professionals Follow-up Study having had an endoscopic procedure between 1986 and 1992, and 175 of 15,339 women of the Nurses' Health Study who had undergone an endoscopy for a variety of reasons between 1980 and 1990. After adjusting for age, family history of colon cancer, history of previous endoscopy, and total energy intake using multiple logistic regression, those consuming 30 g or more of alcohol per day were at increased risk relative to nondrinkers among men (relative risk [RR]=1.69; 95 percent confidence interval [CI]=1.01–2.80) and women (RR=1.79, CI=1.02–3.15). Current smoking also was found to be associated strongly positively with hyperplastic polyps in men (RR=2.45, CI=1.59–3.75) and women (RR=1.96, CI=1.16–2.86). High intake of folate was associated inversely with risk in both men (RR=0.74, CI=0.49–1.11, between high and low intakes of folate) and women (RR=0.45, CI=0.28–0.74, between high and low intakes of folate). Among macronutrients, a suggestive increase in risk existed with intake of animal fat, although this was attenuated in the full multivariate model (RR[men]=1.48, CI=0.94–2.41, and RR [women]=1.22, CI=0.77–1.94) between high and low quantities of animal fat intake. These prospective data provide evidence of associations between low folate intake, alcohol consumption, and current cigarette smoking, and risk of hyperplastic polyps of the distal colon and rectum. These same factors also have been found to be related to adenoma and cancer of the colon. The hyperplastic polyp is an indicator of populations at high risk for colorectal carcinoma, and it also may serve as a marker for factors that influence neoplastic evolution.Drs Giovannucci, Stampfer, Colditz, and Willett are with the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Authors also are affiliated with: the Department of Nutrition, Harvard School of Public Health, Boston, MA (Drs Kearney, Rimm, Stampfer, Ascherio, and Willett); the Department of Epidemiology, Harvard School of Public Health (Drs Rimm, Stampfer, Colditz, Ascherio, and Willett); and the Department of Surgery, New England Deaconess Hospital, Boston, MA (Dr Bleday). Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. This project was supported by research grants number CA 55075 and HL 35464 from the National Institutes of Health and Special Institution Grant No. 18 from the American Cancer Society. Dr Colditz. was supported by a Faculty Research Award (FRA-398) from the American Cancer Society.     

Breastfeeding and breast cancer risk

A population-based case-control study of breast cancer with a focus on premenopausal women under 45 years of age, conducted in three geographic regions of the United States, enabled the evaluation of risk in relation to varying breastfeeding practices. Among premenopausal parous women (1,211 cases, 1,120 random-digit-dialing controls), a history of breastfeeding for two or more weeks was associated with a relative risk (RR) of 0.87 (95 percent confidence interval [CI]=0.7–1.0). This relationship was not altered substantially by removing from the reference group women who had problems with breastfeeding in the first two weeks, including those with insufficient milk production. Risk was not related substantially to number of children breastfed or length of breastfeeding, although a relatively low risk was observed among those breastfeeding for the longest duration examined (RR=0.67, CI=0.4–1.1 for an average period per child of 72 or more weeks). Women who began to breastfeed at a young age (<22 years) experienced the greatest reduction in risk, but other timing parameters (e.g., interval since first or last breastfeeding) were not predictive of risk. Risks were not modified substantially by age or menopause status, although the number of menopausal subjects examined was limited. Use of medications to stop breast milk was unrelated to risk (RR=1.04). The results of this study do not support the notion that breastfeeding substantially reduces breast cancer risk; however, this may reflect the fact that most of our study subjects breastfed only for limited periods of time (average breastfeeding per child of 30 weeks). Further studies are needed to clarify the relationship of breastfeeding to breast cancer risk, and to determine possible etiologic mechanisms underlying any observed associations.Drs Brinton, Potischman, and Swanson are with the Environmental Epidemiology Branch, National Cancer Institute, Betbesda, MD, USA. Authors also are affiliated with the Special Epidemiology Program, New Jersey State Department of Health, Trenton, NJ, USA (Ms Schoenberg); Rollins School of Public Health, Emory University, Atlanta, GA, USA (Dr Coates); the Division of Epidemiology, Columbia University School of Public Health, New York, NY, USA (Dr Gammon); and the Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA (Drs Malone, Stanford, Daling). Address correspondence to Dr Brinton, Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 443, Bethesda, MS 20892, USA.     

Parity and risk of thyroid cancer: a nested case-control study of a nationwide Swedish cohort

The association between parity and risk of thyroid cancer was examined in a case-control study nested within a cohort of Swedish women born 1925–60. A total of 1,409 cases of thyroid cancer were compared with 7,019 agematched controls. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated as estimates of relative risk. A weak association was found between parity and risk of thyroid cancer (OR for ever-parous women cf nulliparous was 1.1, CI=1.0–1.3). For the subset of papillary cancers, there was a significantly increased risk (OR for ever-parous cf nulliparous = 1.3, CI=1.0–1.6), and among women diagnosed at the age of 50 or older, there was a positive linear trend with increasing number of livebirths. Women during the first year after a livebirth had an increased risk of thyroid cancer compared with women who delivered 10 or more years before; this association was most prominent among uniparous women (OR=2.5, CI=1.1–5.9). An increased risk was also apparent for age over 20 years at livebirth (among uniparous women) and age over 25 years at last livebirth (among multiparous women). A negligible effect of parity on thyroid cancer risk was seen, but each livebirth may have a short-term and age-dependent promoting effect.Authors are with the Department of Cancer Epidemiology, University Hospital, Uppsala, Sweden (M.R. Galanti, M. Lambe, A. Ebbora, R. Sparda B. Pettersson): Department of Social Medicine, University Hospital, Uppsala, Sweden (M. Lambe); Department of Epidemiology, Harvard School of Public Health, Boston, USA (A. Ekbom). Address correspondence to Dr M. Rosaria Galanti, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This work was supported in part by grant n. 3136-B92-02XBB from the Swedish Cancer Society.     

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.     

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.     

Differences between Black and White patients with cancer of the uterine corpus in interval from symptom recognition to initial medical consultation (United States)

To determine whether Black women with symptoms of uterine corpus cancer had longer times from symptom recognition to initial medical consultation than did White women in the United States, 331 newly diagnosed patients living in Atlanta (GA), New Orleans (LA), and San Francisco/Oakland (CA) during 1985–87 were interviewed to collect information on symptoms, dates of recognition and consultation, and other factors that might affect the interval. Data were analyzed to estimate medical consultation rates and rate ratios following sysptom recognition. Median recalled times between symptom recognition and consultation were 16 days for Black women and 14 days for White women. Although poverty, having no usual source of healthcare, and other factors were associated with lower consultation rates, the adjusted rate among Black women was only somewhat lower (0.87) than among White women, and the 95 percent confidence interval (CI=0.58–1.31) was consistent with no true difference between the races. In addition, the median time to consultation for women with stage IV cancer was only 15 days longer than the time (14 days) for the women with stage I cancer. These results suggest that time from symptom recognition to initial medical consultation does not contribute importantly to the more advanced stage cancer of the uterine corpus commonly found among Black women.Drs Coates and Eley and Ms Click are with the Department of Epidemiology, Rollins School of Public Health of Emory University, Atlanta, GA (USA). Authors are also with the Division of Cancer Prevention & Control, National Cancer Institute, Rockville, MD (Drs Harlan and Edwards); Department of Pathology Obstetrics and Gynecology, Duke University Medical Center, Durham, NC (Dr Robboy); Forsyth Medical Park, Winston-Salem, NC (Dr Barrett); Environmental Epidemiology Section, California State Department of Health Services, Emeryville, CA (Dr Reynolds); Department of Pathology, Louisiana State University Medical Center, New Orleans, LA (Dr Chen); School of Public Health, University of Massachusetts, Amberst, MA (Dr Darity); Office of the President, Northeastern Ohio Universities College of Medicine, Rootstown, OH (Dr Blacklow). Address correspondence to Dr Coates, Department of Epidemiology, Rollins School of Public Health of Emory University, 1518 Clifton Road, NE, Atlanta, GA 30322, USA. This research was supported in part by contracts N01CN-35042-46, N01CN-05227, N01CN-45174, and N01CN-45176 from the National Cancer Institute, US National Institutes of Health.     

Maternal risk of breast cancer following multiple births: a nationwide study in Sweden

The association between multiple births and subsequent maternal breast cancer risk was explored in a nested case-control study in Sweden encompassing 19,368 parous women with breast cancer diagnosed up to age 65 years, and 100,459 parous controls. Among cases and controls, there were 329 and 2,031 women, respectively, with a history of at least one live multiple birth. Compared with singleton mothers, breast cancer risk was 12 percent lower (odds ratio=0.088, 95 percent confidence interval=0.78–0.99) in women who had had a multiple birth. After stratification for age at diagnosis, evidence of a significant inverse association was found only in women aged 54 years or younger. Birth order of the multiple pregnancy had no apparent risk-modifying effect. Age at earliest multiple birth was unrelated to breast cancer risk. The inverse association between twinning and breast cancer risk may reflect protective physiological features of twin pregnancies. Further research is needed to investigate the role, if any, of in creased levels of steroid hormone-binding globulins in mothers of twins and the proposed inhibitory effects of human chorionic gonadotropin and -fetoprotein, both of which are increased during multiple gestations, on breast carcinogenesis. Breast feeding patterns in mothers of twins also may modify their risk of developing breast cancer.Ambors are with the Department of Cancer Epidemiology (Drs Lambe Ekbom, Adami) and Department of Social Medicine (Lambe), University Hospital, Uppsala, Sweden: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA (Drs Hsieb, Tsilib, Adami, Ekbom, Trichopoulos); UMASS Cancer Center, Worcester, MA, USA (Dr Hsieb). Address correspondece to Dr Lambe, Department of Cancer Epidemiology, University Hospital, S-751 85 Uppsala, Sweden. This project is funded by grants from the Swedish Cencer Societv. the Swedish Societv of Medicine. and the Wahlmarks Fund at Uppsala City Council.     

Dentition,oral hygiene,and risk of oral cancer: a case-control study in Beijing,People's Republic of China

A case-control study of oral cancer was conducted in Beijing, People's Republic of China. The study was hospitalbased and controls were hospital in-patients matched to the cases by age and gender. A total of 404 case/control pairs were interviewed. This paper provides data regarding oral conditions as risk factors for oral cancer, with every patient having an intact mouth examined (pre-operation among cases) using a standard examination completed by trained oral physicians. After adjustment for tobacco smoking and alcohol consumption, poor dentition—as reflected by missing teeth—emerged as a strong risk factor for oral cancer: the odds ratio (OR) for those who had lost 15 – 32 teeth compared to those who had lost none was 5.3 for men and 7.3 for women and the trend was significant (P <0.01) in both genders. Those who reported that they did not brush their teeth also had an elevated risk (OR =6.9 for men, 2.5 for women). Compared to those who had no oral mucosal lesions on examination (OR=1.0), persons with leukoplakia and lichen planus also showed an elevated risk of oral cancer among men and women. Denture wearing per se did not increase oral cancer risk (OR=1.0 for men, 1.3 for women) although wearing metal dentures augmented risk (OR=5.5 for men). These findings indicate that oral hygiene and several oral conditions are risk factors for oral cancer, independently of the known risks associated with smoking and drinking.From the Department of Epidemiology, National Institute of Environmental Health and Engineering, Chinese Academy of Preventive Medicine, Beijing, China (ZT; HH; NS); Unit of Analytical Epidemiology, International Agency for Research on Cancer, Lyon, France (PB; ZT); Beijing Union Hospital (DJ); Cancer Institute, Chinese Academy of Medical Science (JP); Beijing Medical University Stomatological Hospital (MD); Beijing Municipal Stomatological Hospital (SL); University Department of Oral Medicine and Oral Surgery, Bristol Dental Hospital and School, UK (CS); Department of Epidemiology, Harvard School of Public Health (BM; ZT). Address correspondence to Dr Zheng at the Cancer Prevention Research Unit, Yale University, School of Medicine, 26 High Street, New Haven, CT 06510, USA. Dr Zheng was partly supported by a grant from the DuPont Company.     

Histologic types and hormone receptors in breast cancer in men: a population-based study in 282 United States men

Histologic slides from 282 incident cases of breast cancer in men, that were identified in 10 population-based cancer registries in the United States, were reviewed by a single pathologist. Breast cancer more often presented in the noninvasive stage in men (10.8 percent of all cases) than would be expected among women. All noninvasive carcinomas were of the ductal type. Of invasive carcinomas, compared with women, men had smaller proportions of lobular and mucinous types and larger proportions of ductal and papillary types and Paget's disease. No case of tubular or medullary carcinoma was seen. The breast in men is composed only of ducts and normally contains no lobules, and the histologic types of breast carcinomas that predominate in men are likely of ductal origin. Estrogen and progesterone receptors were present in 86.7 percent and 76.3 percent of invasive carcinomas, respectively, which are higher proportions than would be expected among women. Also, unlike findings in women, receptor content was not associated with patient age at diagnosis.Dr Stalsberg is with the Institute of Medical Biology, University of Tromsø, Tromsø, Norway, and Drs Thomas, Rosenblatt, Jimenez, and McTiernan are with the Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, Authors also are affiliated with the University of Illinois, Champaign, IL, USA (Dr Rosenblatt); the Institutio Regional de Investigacion en Salud Publica, Guadalajara, Mexico (Dr Jimenez); the University of Washington School of Medicine, Seattle, WA, USA (Dr McTiernan); the Pharmaceutical Division, CIBAGEIGY Corp., Summit, NJ, USA (Dr Stembagen); the University of Southern Maine, Portland, ME, USA (Dr Thompson); the Connecticut Cancer Epidemiology Unit, New Haven, CT, USA (Dr McCrea Curnen); the School of Public Health, University of California, Berkeley, CA, USA (Dr Satariano); the Resource for Cancer Epidemiology, Department of Health Services, Emeryville, CA, USA (Dr Austin); the School of Public Health, Emory University, Atlanta, GA, USA (Dr Greenberg); the New Mexico Tumor Registry, Albuquerque, NM, USA (Dr Key); the Epidemiology Program, Cancer Research Center of Hawaii, Honolulu, HI, USA (Dr Kolonel); the Northern California Cancer Center, Alameda, CA, USA (Dr West). Address correspondence to Dr Stalsberg, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway. This study was funded by grant number RO1 CA35653 from the US National Cancer Institute.     

Eating frequency—a neglected risk factor for colon cancer?

Eating frequency was examined in relation to risk of cancer of the colon and rectum in a population-based case-control study conducted in Stockholm, Sweden in 1986–88. In the present analysis, 328 cases and 500 controls were included. The adjusted relative risk (RR) of colon cancer per daily eating occasion was 1.2 (95 percent confidence interval [CI]=1.1–1.4, adjusted for year of birth, sex, intake of energy, fat, protein, and fiber, browning of meat surface, physical activity, and body mass index). The corresponding RR for rectal cancer was 1.0 (CI=0.9–1.2). The frequency of eating snacks was related to risk of colon cancer (RR per snack = 1.6, CI=1.2–1.9), while the frequency of eating meals (breakfast, lunch, or dinner) was not (RR per meal = 0.8, CI=0.6–1.1). The results are consistent with findings in two other case-control studies in which eating frequency was found to be a risk factor for colon cancer.Dr Gerhardsson de Verdier is with the Department of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, and the Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, CA, USA. Dr Longnecker is with the Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA, USA. Address correspondence to Dr Gerhardsson de Verdier at the Institute of Environmental Medicine, Department of Epidemiology, Box 60208, S-104 01, Stockholm, Sweden. The study was supported by two grants (2228-B86-013XA; 2228-B87-02XA) from the Swedish National Cancer Society. Dr Longnecker is the recipient of a Junior Faculty Research Award from the American Cancer Society.     

Physical activity, obesity, and risk of colorectal adenoma in women (United States)

The relationship between physical inactivity, body mass index (BMI) (wt[kg]/ht[m]²), and pattern of adipose distribution with risk of colorectal adenomas (precursors of cancer) was examined in 13,057 female nurses in the United States, 40 to 65 years of age in 1986, who had an endoscopy between 1986 and 1992. From 1986 to 1992, 439 participants were newly diagnosed with adenomas of the distal colorectum. After controlling for age, prior endoscopy, parental history of-colorectal cancer, smoking, aspirin, and intakes of animal fat, dietary fiber, folate, methionine, and alcohol, physical activity was associated inversely with risk of large (1 cm) adenomas in the distal colon (relative risk [RR]=0.57,95 percent confidence interval [CI]=0.30–1.08, comparing high and low quintiles of average weekly energy expenditure from leisure-time activities; P trend = 0.05). Much of the benefit came from activities of moderate intensity such as brisk walking. In addition, BMI was associated directly with risk of large adenomas in the distal colon (multivariate RR=2.21 [CI=1.18–4.16], P trend = 0.0001, for BMI 29 cf <21 kg/m²). Waist circumference and the waist-to-hip ratio (WHR) were not related significantly to adenoma independently of BMI, but women with both a high BMI and high WHR were at greater risk of large colon adenoma (multivariate RR=1.99, CI=0.98–4.05) than women with high BMI but relatively low WHR (multivariate RR=1.35, CI=0.61–2.97). BMI was not related to small (<1 cm) adenoma risk but physical activity had an inverse association with small adenomas in the distal colon (multivariate RR=0.68, CI=0.40–1.15, P trend = 0.03). The relationships between BMI or physical activity were considerably weaker and inconsistent for rectal adenomas. These results, in women, support an inverse association between physical activity and occurrence or progression of ademonas in the distal colon; obesity is associated with an elevated risk of large adenomas.The authors are with the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. The authors are also affiliated with the Department of Nutrition, Harvard School of Public Health, Boston, MA (Drs Giovannucci, Stampfer, and Willett), and the Department of Epidemiology, Harvard School of Public Health, Boston, MA (Drs Colditz, Stampfer, and Willett). Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. The work was supported by research grant numbers CA 40935 and CA 55075 from the US National Institutes of Health. Dr Colditz is supported by a Faculty Research Award (FRA-398) from the American Cancer Society.     

A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States)

To evaluate predictors of contralateral breast cancer risk, we examined data from a nested case-control study of second primary cancers among a cohort of women in western Washington (United States) diagnosed with breast cancer during 1978 through 1990 and identified through a population-based cancer registry. Cases included all women in the cohort who subsequently developed contralateral breast cancer at least six months after the initial diagnosis, but prior to 1992 (n=234). Controls were sampled randomly from the cohort, matched to cases on age, stage, and year of initial breast cancer diagnosis. Information on potential risk factors for second primary cancer was obtained through medical record abstractions and physician questionnaires. Women who were postmenopausal due to a bilateral oophorectomy (i.e., a surgical menopause) at initial breast cancer diagnosis had a reduction in contralateral breast cancer risk compared with premenopausal women (matched odds ratio [mOR]=0.25, 95 percent confidence interval [CI]=0.09–0.68), whereas no reduction in risk was noted among postmenopausal women who had had a natural menopause (mOR=0.90, CI=0.39–2.09). Among postmenopausal women, there was a suggestion of a lower risk associated with relatively high parity (2+). A family history of breast cancer was associated with an increased risk (mOR=1.96, CI=1.22–5.15) and varied little by menopausal status. Having an initial tumor with a lobular component (c.f. a ductal histology) was not related strongly to risk (mOR=1.47, CI=0.79–2.74). The results of the present and earlier studies argue that we have limited ability to predict the occurrence of a contralateral breast tumor. Better predictors will be required before diagnostic and preventive interventions can be targeted to subgroups of patients with unilateral breast cancer.Authors are with the Department of Epidemiology, University of Washington, Seattle, WA, USA (Drs Cook, White, Schwartz, Daling, Weiss); with the Fred Hutchinson Cancer Research Center, Seattle, WA (Drs Cook, White, Schwartz, McKnight, Daling, Weiss); and the Department of Biostatistics, University of Washington, Seattle, WA (Dr McKnight). Address correspondence to Dr Cook, MP-381, Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104, USA. This research was supported in part by grants from the US National Cancer Institute (R35 CA 39779), the Agency for Health Care Policy and Research (1 RO3 HS08004-01), and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-CN-05230 from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center.     

Use of oral contraceptives and breast cancer risk: The Norwegian-Swedish Women's Lifestyle and Health Cohort Study.

Current use of oral contraceptives (OCs) has been reported to increase breast cancer risk slightly. In 1991/1992, a prospective cohort study specifically designed to examine the role of hormonal contraceptives in relation to breast cancer was conducted in Norway and Sweden. This study was entitled Women's Lifestyle and Health. Of 196,000 invited women aged 30-49 years, 106,844 women answered a 4-page questionnaire. Altogether, 103,027 women providing information on contraceptive use were included in the analysis presented here, and 1,008 primary invasive breast cancers were diagnosed throughout 1999 (end of follow-up). Proportional hazard regression was used to calculate relative risks (RRs) with adjustment for age and other possible confounders. An increased breast cancer risk was observed among women who were current/recent users of OCs of any type at the start of follow-up [RR, 1.6; 96% confidence interval (CI), 1.2-2.1]. Current/recent use (i.e., use in the year preceding cohort enrolment) of combined OCs (RR, 1.5; 95% CI, 1.0-2.0) and progestin-only pills (RR, 1.6; 95% CI, 1.0-2.4) entailed similar levels of increased risk. An increased risk of borderline significance was found among short-term (i.e., less than 13 months) users before age 20 years (RR, 1.3; 95% CI, 1.0-1.7) and before first full-term pregnancy (RR, 1.4; 95% CI, 1.0-1.8). Long-term users of OCs were at a higher risk of breast cancer than never users (test for trend, P = 0.005). Current/recent use of OCs is associated with an increased breast cancer risk. Use of combined OCs and progestin-only pills seem to increase the risk at the same level.     

Recall and selection bias in reporting past alcohol consumption among breast cancer cases

Recall and selection bias are well-recognized potential problems in case-control studies of alcohol and cancer, but few analyses have attempted to assess the direction and the magnitude of these potential biases. We thus examined alcohol consumption in relation to risk of breast cancer using dietary questionnaires administered both before and after the diagnosis of breast cancer in the Nurses' Health Study (United States). Among cohort members who completed a dietary questionnaire in 1986 and who were free of cancer, 616 were diagnosed with breast cancer during follow-up to December 1989. These cases and 1,277 controls (a random sample of cohort members who did not develop cancer up to 1990) then were sent another questionnaire inquiring about their diet in 1985. Four hundred and ninety-four cases (80.2 percent) and 999 controls (78.2 percent) responded to the second questionnaire. The analysis based on the prospective (1986) questionnaire demonstrated an elevated risk of breast cancer among women who drank 30 or more g of alcohol daily (about two drinks) relative to nondrinkers (odds ratio [OR]=1.55, 95 percent confidence interval [CI]=1.01–2.39). The analysis based on the retrospective questionnaire also indicated a similar but slightly attenuated elevation of risk of breast cancer among women who drank at least 30 g daily (OR=1.42, CI=0.85–2.40). In these data, bias due to selection and recall had only minor effects on reported intake of alcohol consumption.Drs Giovannucci, Stampfer, Colditz, Manson, Rosner, Speizer, and Willett are with Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Drs Colditz, Stampfer, and Willett are also with the Harvard School of Public Health, Boston, MA, USA. Dr Longnecker is with the University of California School of Public Health, Los Angeles, CA, USA. Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. The project was supported by research grant number CA 40935 and CA 55075 from the US National Institutes of Health.     

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.     

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.     

Progestogen-only oral contraceptives and risk of breast cancer in New Zealand

Little is known about the influence of progestogen-only contraceptives on a woman's risk of breast cancer. This issue was examined in a national population-based case-control study 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. Use of progestogen-only pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who had ever used progestogen-only pills was estimated to be 1.1 (95 percent confidence interval [CI]=0.73–1.5). In women aged 25 to 34 years, the RR was 2.3 (CI=1.2–4.3). Women who had started using progestogen-only pills within the last 10 years were at increased risk of breast cancer (RR=1.6, CI=1.0–2.4), whereas those who had first used them earlier were at significantly reduced risk (RR=0.44, CI=0.22–0.90). These findings are similar to results for depot medroxyprogesterone acetate, and a possible analogy with the influence of pregnancy is also suggested.The anthors are with the Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. Address correspondence to: Dr Skegg, Department of Preventive and Social Medicine, University of Otago Medical School, P. O. Box 913, Dunedin, New Zealand. This research was supported by grants from the Medical Research Council of New Zealand and from the Special Program of Research, Development, and Research Training in Human Reproduction, World Health Organization.