Summary
While there is evidence that breast cancer risk is positively associated with body mass index (in postmenopausal women) and energy intake and inversely associated with physical activity, few studies have examined breast cancer risk in association with energy balance, the balance between energy intake and expenditure. Therefore, in the cohort study reported here, we studied the independent and combined associations of vigorous physical activity, energy consumption, and body mass index (BMI), with breast cancer risk. The investigation was conducted in 49,613 Canadian women who were participants in the National Breast Screening Study (NBSS) and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 2545 incident breast cancer cases. Due to exclusions for various reasons, the analyses were based on 40,318 subjects amongst whom there were 1673 incident cases of breast cancer. Participation in vigorous physical activity and body mass index were not independently associated with breast cancer risk in the total cohort. A statistically significant positive trend was observed, however, between energy intake and breast cancer risk (P trend = 0.01). Although there was some variation in risk associated with vigorous physical activity, and BMI when the analyses were stratified by menopausal status, these interactions were not statistically significant. The interaction between menopausal status and energy intake, however, was of borderline statistical significance (P interaction = 0.06), with a statistically significant increased risk of breast cancer associated with highest versus lowest quartile of energy intake among premenopausal women (Hazard Ratio [HR] = 1.45, 95% confidence interval [CI] = 1.13– 1.85, P trend = 0.001). There was evidence of an increased risk of breast cancer associated with a relatively high body mass index among postmenopausal women in the highest quartile level of energy intake (Hazard Ratio [HR] = 1.72, 95% confidence interval [CI] = 1.01– 2.93, P trend = 0.05). In addition, there was evidence of an increased risk of breast cancer among premenopausal, physically inactive, overweight/obese women who consumed ≥1972 kcal/day compared to physically active normal weight women who consumed <1972 kcal/day (HR = 1.60, 95% CI = 1.08–2.37). Our data suggest that obese premenopausal women with relatively high energy intake may be at increased risk of breast cancer. In addition, energy imbalance, represented by a relatively high energy intake, lack of participation in vigorous physical activity, and a relatively high body mass index, may be associated with increased breast cancer risk, particularly among premenopausal women.
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References
Willett WC, Stampfer MJ: 1998. Implications of total energy intake and epidemiologic analyses. In: Willett WC, (ed). Nutritional Epidemiology. New York (NY), Oxford University Press, 273–301
Ellison PT: 1995. Understanding natural variation in human ovarian function. In: Dunbar RIM (ed). Human Reproductive Decisions: Biological and Social Perspectives. New York, St. Martin’s Press
Key TJ, Allen NE, Verkasalo PK, Banks E: Energy balance and cancer: the role of sex hormones. Proc Nutr Soc 60:81–89, 2001
Henderson B, Feigelson HS: Hormonal carcinogenesisCarcinogenesis 21:427–433, 2000
Mellemkjaer L, Emborg C, Gridley G, Munk-Jorgensen P, Johansen C, Tjonneland A, Kjaer SK, Olsen JH: Anorexia nervosa and cancer riskCancer Causes Control 12:173–177, 2001
Nilsen TI, Vatten LJ: Adult height and risk of breast cancer: a possible effect of early nutritionBr J Cancer 85:959–961, 2001
Robsahm TE, Tretli S: Breast cancer incidence in food- vs. non-food producing areas in Norway: possible beneficial effects of World War IICancer Causes Control 86: 362–366, 2002
Michels KB, Ekbom A: Caloric restriction and incidence of breast cancerJ Am Med Assoc 291: 1226–1230, 2004
Friedenreich CM, Rohan TE: A review of physical activity and breast cancerEpidemiology 6: 311–317, 1995
Lee IM, 2003 Physical activity and cancer prevention—data from epidemiologic studiesMed Sci Sport Exer 35: 1823–1827
IARC: 2002. Handbooks on Cancer Prevention, Weight Control and Physical Activity. Lyon, IARC Press
Hunter DJ, Willett WC: Diet, body size, and breast cancerEpidemiol Rev 15: 110–132, 1993
van den Brandt PA, Spiegelman D, Yuan SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, Marshall JR, Miller AB, Rohan TE, Smith-Warner SA, Speizer FE, Willett WC, Wolk A, Hunter DJ: Pooled analysis of prospective cohort studies on height, weight, and breast cancer riskAm J Epidemiol 152: 514–527, 2000
Dirx MJM, Voorrips LE, Goldbohm RA, van den Brandt PA: Baseline recreational physical activity, history of sports participation, and postmenopausal breast carcinoma risk in the Netherlands Cohort StudyCancer 92: 1638–1649, 2001
Malin A, Matthews CE, Shu XO, Cai H, Dai Q, Jin F, Gao YT, Zheng W: Energy balance and breast cancer riskCancer Epidem Biomar14: 1496–1501, 2005
Terry PD, Jain M, Miller AB, Howe GR, Rohan TE: Dietary carotenoid intake and colorectal cancer riskNutr Cancer 42: 167–172, 2002
Miller AB, Baines CJ, To T, Wall C: Canadian National Breast Screening Study. I. Breast cancer detection and death rates among women aged 40–49 years. II. Breast cancer detection and death rates among women aged 50–59 yearsCan Med Assoc J 147: 1459–1488, 1992
Jain M, Harrison L, Howe GR, Miller AB: Evaluation of a self-administered dietary questionnaire for use in a cohort studyAm J Clin Nutr 36: 931–935, 1982
Watt BK, Merrill A: Composition of Foods: Raw, processed, prepared. Department of Agriculture, 1972
Jain M, Howe GR, Rohan TE: Dietary assessment in epidemiology: Comparison of food frequency and a diet history questionnaire with a 7-day food recordAm J Epidemiol 143: 953–960, 1996
Jain M, Miller AB, Tumor characteristics and survival of breast cancer patients in relation to premorbid diet and body sizeBreast Cancer Res Tr 42: 43–55, 1997
Rothman KJ, Greenland S: 1998. Modern Epidemiology. Philadelphia (PA), Lippincott-Raven, p 319
Albanes D: 1987. Total calories, body weight, and tumor incidence in miceCancer Res 47:1987–1992
Franceshi S, Favero A: The role of energy and fat in cancers of the breast and colon-rectum in a southern European populationAnn Oncol 10: S61–S63, 1999
Dirx MJM, Zeegers MPA, Dagnelie PC, van den Bogaard T, van den Brandt PA: Energy restriction and the risk of spontaneous mammary tumors in mice: a meta-analysisInt J Cancer 106: 766–770, 2003
Klurfeld DM, Welch CB, Lloyd LM, Kritchevsky D: Determination of degree of energy restriction necessary to reduce DMBA-induced mammary tumorigenesis in rats during the promotion phaseJ Nutr 119: 286–291, 1989
Elias SG, Peeters PHM, Grobbee DE, van Noord PA: Breast cancer risk after caloric restriction during the 1944–1945 Dutch famineJ Natl Cancer Inst 96: 539–546, 2004
Dirx MJM, van den Brandt PA, Goldbohm RA, Lumey LH: Diet in adolescence and the risk of breast cancer: results of The Netherlands Cohort StudyCancer Causes Control 10: 189–199, 1999
McTiernan A, Tworoger SS, Ulrich CM, Yasui Y, Irwin ML, Rajan KB, Sorensen B, Rudolph RE, Bowen D, Stanczyk FZ, Potter JD, Schwartz RS: Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trialCancer Res 64: 2923–2928, 2004
McTiernan A, Tworoger SS, Rajan KB, Yasui Y, Sorenson B, Ulrich CM, Chubak J, Stanczyk FZ, Bowen D, Irwin ML, Rudolph RE, Potter JD, Schwartz RS: Effect of exercise on serum androgens in postmenopausal women: a 12–month randomized clinical trialCancer Epidemiol Biomar13: 1099–1105, 2004
Ainsworth P, Sternfeld B, Slattery ML, Daguise V, Zahm SH: Physical activity and breast cancerCancer 83: 611–20, 1998
Ballard-Barbash R, Swanson CA: Body weight: Estimation of risk for breast and endometrial cancersAm J Clin Nutr 63: 437S–441S, 1996
London SJ, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Speizer FE: Prospective study of relative weight, height, and risk of breast cancerJ Am Med Assoc 262: 2853–2858, 1989
Folsom AR, Kaye SA, Prineas RJ, Potter JD, Gapstur SM, Wallace RB: Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal womenAm J Epidemiol 131: 794–803, 1990
van den Brandt PA, Dirx MJM, Ronckers CM, van den Hoogen P, Goldbohm RA: Height, weight, weight change, and postmenopausal breast cancer risk: the Netherlands Cohort StudyCancer Causes Control 8: 39–47, 1997
Vatten LJ, Kvinnsland S: Body mass index and risk of breast cancer: a prospective study of 23,826 Norwegian womenInt J Cancer 45: 440–444, 1990
Tornberg SA, Holm LE, Carstensen JM: Breast cancer risk in relation to serum cholesterol, serum beta-lipoprotein, height, weight, and blood pressureActa Oncol 27: 31–37, 1988
De Stavola BL, Wang DY, Allen SD, Giaconi J, Fentiman IS, Reed MJ, Bulbrook RD, Hayward JL: The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom)Cancer Causes Control 4: 331–340, 1993
de Waard F, Baanders-van Halewijin EA,: A prospective study in general practice on breast cancer risk in postmenopausal womenInt J Cancer 14: 153–160, 1974
Goodman MT, Cologne JB, Moriwaki H, Vaeth M, Mabuchi K: Risk factors for primary breast cancer in Japan: 8-year follow-up of atmoic bomb survivorsPrev Med 26: 144–153, 1997
den Tonkelaar I, Seidell JC, Collette HJA, de Waard F: A prospective study on obesity and subcutaneous fat patterning in relation to breast cancer in postmenopausal women participating in the DOM-projectBr J Cancer 69: 352–357, 1992
Judd HL, Shamonki IM, Frumar AM, Lagasse LD: Origin of serum estradiol in postmenopausal womenObstet Gynecol 59: 680–686, 1982
Siiteri PK, Hammond GL, Nisker JA: 1981. Increased availability of serum estrogens in breast cancer: a new hypothesis. In: Pike MC, Siiteri PK, Welsch CW (eds). Hormones and Breast Cancer. Banbury Report 8. Cold Spring Harbor (NY), Cold Spring Harbor Laboratory Press, 87–106
Patel AV, Calle EE, Bernstein L, Wu AH, Thun MJ: Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US womenCancer Causes Control 14: 519–529, 2003
McKeown-Eyssen G: Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol Biomar 3, 1994
Lawlor DA, Smith GD, Ebrahim S: Hyperinsulinemia and increased risk of breast cancer: findings from the British women’s heart and health studyCancer Causes Control 15: 267–275, 2004
Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ: Insulin resistance and breast-cancer riskInt J Cancer 52: 511–516, 1992
Ellison PT: Reproductive ecology and reproductive cancers. In: Panter-Brick C, Worthman CM (eds). Hormones, Health, and Behavior. A Socio-Ecological and Lifespan Perspective. Cambridge, Cambridge University Press, 1999
Friedenreich CM: 2001. Review of anthropometric factors and breast cancer riskEur J Cancer Prev 10: 15–32
Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC: Calorie restriction, aging and cancer prevention: Mechanisms of action and applicability to humansAnn Rev Med 54: 131–152, 2003
Kritchevsky D: 1993 Undernutrition and chronic disease: cancerProc Nutr Soc 52: 39–47
Kaaks R, Lukanova A: Energy balance and cancer: the role of insulin and insulin-like growth factor-IProc Nutr Soc 60: 91–106, 2001
Berrigan D, Perkins SN, Haines DC, Hursting SD: Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient miceCarcinogensis 23: 817–822, 2002
Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, Barrett JC: Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient miceCancer Res 57: 4667–4672, 1997
Hursting SD, Switzer BR, French JE, Kari FW: The growth hormone: insulin-like growth factor 1 axis is a mediator of diet restriction-induced inhibition of mononuclear cell leukemia in Fischer ratsCancer Res 53: 2750–2757, 1993
Ruggeri BA, Klurfeld DM, Kritchevsky D, Furlanetto RW: Caloric restriction and 7,12-dimethylbenz(a)-anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II and epidermal growth factorCancer Res 49: 4130–4134, 1989
Campagnoli C, Biglia N, Belforte P, Botta D, Pedrini E, Sismondi P: Post-menopausal breast cancer risk: oral estrogen treatment, abdominal obesity induce opposite changes in possibly important biological variablesEur J Gynaecol Oncol 13: 139–154, 1992
Jones JI, Clemmons DR: Insulin-like growth factors and their binding proteins: biological actionsEndocr Rev 16: 3–34, 1995
Stewart CE, Rotwein P: Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factorsPhysiol Rev 76: 1005–1026, 1996
Werner H, LeRoith D: The role of the insulin-like growth factor system in human cancerAdv Cancer Res 68: 183–223, 1996
Fletcher O, Gibson L, Johnson N, Altmann DR, Holly JM, Ashworth A, Peto J, Silva Idos S: Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic reviewCancer Epidemiol Biomark14: 2–19, 2005
MMWR: Prevalence of physical activity, including lifestyle activities among adults–United States, 2000–2001Morb Mortal Wkly Rep 52: 764–769, 2003
Bedard D, Shatenstein B, Nadon S: Underreporting of energy intake from a self-administered food-frequency questionnaire completed by adults in MontrealPublic Health Nutr 7: 675–681, 2004
Klesges RC, Eck LH, Ray JW: Who underreports dietary intake in a dietary recall? Evidence from the Second National Health and Nutrition Examination SurveyJ Consult Clin Psychol 63: 438–444, 1995
Robles SC, Marrett LD, Clarke EA, Risch EA: An application of capture-recapture methods to the estimation of completeness of cancer registrationJ Clin Epidemiol 41: 495–501, 1988
Shannon HS, Jamieson E, Walsh C, Julian JA, Fair ME, Buffet A: Comparison of individual follow-up and computerized record linkage using the Canadian Mortality Data BaseCan J Public Health 80: 54–57, 1989
Acknowledgements
Funded in part by the National Cancer Institute of␣Canada. We thank Statistics Canada, the provincial and territorial Registrars of Vital Statistics, and the Cancer Registry directors for their assistance in making the cancer incidence and mortality data available.
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Silvera, S.A.N., Jain, M., Howe, G.R. et al. Energy balance and breast cancer risk: a prospective cohort study . Breast Cancer Res Treat 97, 97–106 (2006). https://doi.org/10.1007/s10549-005-9098-3
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DOI: https://doi.org/10.1007/s10549-005-9098-3