Modifying the risk associated with obesity

Obesity is one of the few risk factors for breast cancer   that   can   be   modified   throughout life.  Positive   lifestyle   choices   that   control obesity,  such as adhering to a healthy diet and regular physical activity,  can have a significant positive impact on the incidence and prognosis of breast cancer [53].  It has been suggested that reducing obesity would decrease the incidence of breast cancer by one-tenth   in   Europe,  with   a   consequent reduction in mortality rates [54]. The Cancer Prevention Study II concluded that up to 18 000 deaths in US women aged >50 years could be avoided if women maintained a BMI of <25 throughout their adult life [9].

In addition, some investigators have argued that increasing physical activity and decreasing body   fat   are   reasonable   interventions   to decrease   insulin   and   leptin   levels,  which may improve the prognosis of breast cancer [55].  Follow-up data from several long-term cohort studies support the hypothesis that lifestyle factors such as diet and physical activity may improve the prognosis of women diagnosed with breast cancer [56].  However,  another   factor   to   consider   is   that   weight gain is also a common side effect in women receiving adjuvant chemotherapy,  which may have   negative   long-term   implications   for survival [57,58].

A   consistent,  independent,  and   positive association has been found between obesity and the development of breast cancer in postmenopausal women, and a preponderance of   the   literature   supports   an   association between obesity and a poor breast cancer prognosis in both pre-  and postmenopausal women. 

In   the   future,  it   is   feared   that the effect of the increasing prevalence of obesity (especially in the western world) will manifest as an increased incidence of breast cancer among postmenopausal women,  and that this rising rate of obesity may limit the reduction in breast cancer-related mortality that   may   otherwise   have   resulted   from improvements in the detection and treatment of   breast   cancer.  Obesity,  regardless   of how   it   is   assessed,  adversely   affects   the development and prognosis of breast cancer.

There are ample data to suggest that obese and physically inactive breast cancer patients have a poorer survival rate compared with lighter   weight   and   more   active   women.

Despite complex and at times controversial data,  enough evidence is presently available to suggest that weight management should be a part of the strategy to prevent breast cancer development, recurrence, and death. Curbing the twin epidemics of obesity and breast cancer demands not only changes in diet and lifestyle at an individual level,  but also changes in the political, physical, and social environment. Weight management, with diet and lifestyle advice or interventions,  should be an integral part of the follow-up of breast cancer patients.

Address for correspondence: AR Carmichael, Consultant Surgeon, Russells Hall Hospital, Dudley, DY1 2HQ, UK.
Email: .(JavaScript must be enabled to view this email address)


1.  Calle EE, Rodriguez C, Walker-Thurmond K et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348:1625–38.

2.  Bergstrom A, Pisani P, Tenet V et al. Overweight as an avoidable cause of cancer in Europe. Int J Cancer 2001;91:421–30.

3.  Reeves GK, Pirie K, Beral V et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 2007;335:1134.

4.  La Vecchia C, Negri E, Franceschi S et al. Body mass index and post-menopausal breast cancer: an age-specific analysis. Br J Cancer 1997;75:441–4.

5.  Ballard-Barbash R, Swanson CA. Body weight: estimation of risk for breast and endometrial cancers. Am J Clin Nutr 1996;63:437–41S.

6.  Lahmann PH, Lissner L, Berlund G. Breast cancer risk in overweight postmenopausal women. Cancer Epidemiol Biomarkers Prev 2004;13:1414.

7.  Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol 2002;20:1128–43.

8.  Carmichael AR. Obesity and prognosis of breast cancer. Obes Rev 2006;7:333–40.

9.  Petrelli JM, Calle EE, Rodriguez C et al. Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control 2002;13:325–32.

10.  Ryu SY, Kim CB, Nam CM et al. Is body mass index the prognostic factor in breast cancer?: a meta-analysis. J Korean Med Sci 2001;16:610–4.

11.  Daling JR, Malone KE, Doody DR et al. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 2001;92:720–9.

12.  Carmichael AR, Bendall S, Lockerbie L et al. Does obesity compromise survival in women with breast cancer? Breast 2004;13:93–6.

13.  Carmichael AR, Bates T. Obesity and breast cancer: a review of the literature. Breast 2004;13:85–92.

14.  Enger SM, Greif JM, Polikoff J et al. Body weight correlates with mortality in early-stage breast cancer. Arch Surg 2004;139:954–8.

15.  Chang S, Alderfer JR, Asmar L et al. Inflammatory breast cancer survival: the role of obesity and menopausal status at diagnosis. Breast Cancer Res Treat 2000;64:157–63.

16.  McTiernan A, Rajan KB, Tworoger SS et al. Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 2003;21:1961–6.

17.  Key TJ, Appleby PN, Reeves GK et al.; Endogenous Hormones Breast Cancer Collaborative Group. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 2003;95:1218–26.

18.  Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev 2004;5:153–65.

19.  Goodwin PJ, Ennis M, Fantus IG et al. Is leptin a mediator of adverse prognostic effects of obesity in breast cancer? J Clin Oncol 2005;23:6037–42.

20.  Tannenbaum A. Relationship of body weight to cancer incidence. Arch Pathol 1940;30:509–17.

21.  Kesteloot H, Sasaki S, Verbeke G et al. Cancer mortality and age: relationship with dietary fat. Nutr Cancer 1994;22:85–98.

22.  Pierce JP, Faerber S, Wright FA et al. A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women’s Healthy Eating and Living (WHEL) Study. Control Clin Trials 2002;23:728–56.

23.  Pierce JP, Natarajan L, Caan BJ et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA 2007;298:289–98.

24.  Blackburn GL, Wang KA. Dietary fat reduction and breast cancer outcome: results from the Women’s Intervention Nutrition Study (WINS). Am J Clin Nutr 2007;86:S878–81.

25.  Karagiannides I, Pothoulakis C. Obesity, innate immunity and gut inflammation. Curr Opin Gastroenterol 2007;23:661–6.

26.  Schrijvers CT, Mackenbach JP, Lutz JM et al. Deprivation and survival from breast cancer. Br J Cancer 1995;72:738–43.

27.  Macleod U, Ross S, Gillis C et al. Socio-economic deprivation and stage of disease at presentation in women with breast cancer. Ann Oncol 2000;11:105–7.

28.  Brown SB, Hole DJ, Cooke TG. Breast cancer incidence trends in deprived and affluent Scottish women. Breast Cancer Res Treat 2007;103:233–8.

29.  Holmes MD, Chen WY, Feskanich D et al. Physical activity and survival after breast cancer diagnosis. JAMA 2005;293:2479–86.

30.  Pierce JP, Stefanick ML, Flatt SW et al. Greater survival after breast cancer in physically active women with high vegetable–fruit intake regardless of obesity. J Clin Oncol 2007;25:2345–51.

31.  Holick CN, Newcomb PA, Trentham-Dietz A et al. Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 2008;17:379–86.

32.  Connolly BS, Barnett C, Vogt KN et al. A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutr Cancer 2002;44:127–83.

33.  Borugian MJ, Sheps SB, Kim-Sing C et al. Waist-to-hip ratio and breast cancer mortality. Am J Epidemiol 2003;158:963–8.

34.  Cui Y, Whiteman MK, Flaws JA et al. Body mass and stage of breast cancer at diagnosis. Int J Cancer 2002;98:279–83.

35.  Chagpar AB, McMasters KM, Saul J et al. Body mass index influences palpability but not stage of breast cancer at diagnosis. Am Surg 2007;73:555–60.

36.  Reinier KS, Vacek PM, Geller BM. Risk factors for breast carcinoma in situ versus invasive breast cancer in a prospective study of pre- and post-menopausal women. Breast Cancer Res Treat 2007;103:343–8.

37.  Ingram D, Nottage E, Ng S et al. Obesity and breast disease. The role of the female sex hormones. Cancer 1989;64:1049–53.

38.  Verreault R, Brisson J, Deschenes L et al. Body weight and prognostic indicators in breast cancer. Modifying effect of estrogen receptors. Am J Epidemiol 1989;129:260–8.

39.  Schapira DV, Kumar NB, Lyman GH et al. Obesity and body fat distribution and breast cancer prognosis. Cancer 1991;67:523–8.

40.  Daniell HW. Increased lymph node metastases at mastectomy for breast cancer associated with host obesity, cigarette smoking, age, and large tumor size. Cancer 1988;62:429–35.

41.  Derossis AM, Fey JV, Cody HS 3rd et al. Obesity influences outcome of sentinel lymph node biopsy in early-stage breast cancer. J Am Coll Surg 2003;197:896–901.

42.  Goffman TE, Laronga C, Wilson L et al. Lymphedema of the arm and breast in irradiated breast cancer patients: risks in an era of dramatically changing axillary surgery. Breast J 2004;10:405–11.

43.  Newman LA, Kuerer Hm, McNeese MD et al. Reduction mammoplasty improves breast conservation therapy in patients with macromastia. Am J Surg 2001;181:215–20.

44.  Madarnas Y, Sawka CA, Franssen E et al. Are medical oncologists biased in their treatment of the large woman with breast cancer? Breast Cancer Res Treat 2001;66:123–33.

45.  Rosner GL, Hargis JB, Hollis DR et al. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from Cancer and Leukemia Group B study 8541. J Clin Oncol 1996;14:3000–8.

46.  Bastarrachea J, Hortobagyi GN, Smith TL et al. Obesity as an adverse prognostic factor for patients receiving adjuvant chemotherapy for breast cancer. Ann Intern Med 1994;120:18–25.

47.  Poikonen P, Blomqvist C, Joensuu H. Effect of obesity on the leukocyte nadir in women treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil dosed according to body surface area. Acta Oncol 2001;40:67–71.

48.  Mehta RR, Beattie CW, Das Gupta TK et al. Endocrine profile in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat 1992;20:125–32.

49.  Altundag K, Altundag O, Morandi P et al. Obesity may decrease the amenorrhea associated with chemotherapy in premenopausal breast cancer patients. Ann Oncol 2005;16:333.

50.  McTiernan A, Wu L, Chen C et al.; Women’s Health Initiative Investigators. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 2006;14:1662–77.

51.  Dignam JJ, Wieand K, Johnson KA et al. Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 2003;95:1467–76.

52.  Sellahewa C, Nightingale P, Carmichael AR. Obesity and HER 2 overexpression: a common factor for poor prognosis of breast cancer. Int Semin Surg Oncol 2008;5:2.

53.  Carmichael AR. Obesity as a risk factor for development and poor prognosis of breast cancer. BJOG 2006;113:1160–6.

54.  Kelsey JL, Bernstein L. Epidemiology and prevention of breast cancer. Annu Rev Public Health 1996;17:47–67.

55.  Irwin ML, McTiernan A, Bernstein L et al. Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2005;14:2881–8.

56.  Chlebowski RT, Rose D, Buzzard IM et al. Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management. The Women’s Intervention Nutrition Study (WINS). Breast Cancer Res Treat 1992;20:73–84.

57.  Harvie MN, Campbell IT, Baildam A et al. Energy balance in early breast cancer patients receiving adjuvant chemotherapy. Breast Cancer Res Treat 2004;83:201–10.

58.  Makari–Judson G, Judson CH, Mertens WC. Longitudinal patterns of weight gain after breast cancer diagnosis: observations beyond the first year. Breast J 2007;13:258–65.

Amtul R Carmichael, MD
Russells Hall Hospital, Dudley, UK

Provided by ArmMed Media