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World Journal of Oncology

Original Article

Volume 4, Number 4-5, October 2013, pages 188-193

Female Body Mass Index and its Relationship With Triple Negative Breast Cancer and Ethnicity

Body mass index is a modifiable risk factor that has been associated with several co-morbidities, including type 2 Diabetes, risk of cardiovascular diseases and various types of cancers, to name a few [1, 2]. This is an alarming development especially in a country such as ours, where two-third of the US population in either overweight or obese [1]. Several studies have shown a strong association between body mass index and the risk of developing breast cancers in post-menopausal women [3-10]. On the other hand, the association between breast cancer in premenopausal women and body mass index favors a more inverse relationship [11-17] where the protective role of estrogen is thought to protect against the development of breast cancer [18-21]. Here we explore the relationship between body mass index, triple negative breast cancer and ethnicity at our inner city university hospital.

We present a retrospective review of the Tumor Registry Database at the University of Florida, College of Medicine in Jacksonville. It involved patients diagnosed with breast cancer between 2004 and 2008. After the IRB approval, 84 patients with triple negative breast cancer were identified. Triple negative breast cancer is defined as the type of breast cancer with negative receptors for estrogen(ER), progesterone (PR), and unremarkable for the expression of HER2/Neu. For comparison, 83 control patients were randomly selected with breast cancer having at least one hormone receptors positive in the tumor profile. The data was electronically collected and later arranged into variables such as breast cancer receptor status, body mass index and ethnicity. Chi-square testing was then used to evaluate categorical variables while T-Test analysis was used for continuous variables.

Our data demonstrated that 27.4% of the triple negative breast cancer patients had a BMI < 25 compared to the 14.5% of non-triple negative breast cancer, 73.6% of the triple negative breast cancer group had a BMI ≥ 25 compared to 86.5% in the non-triple negative group (p-value 0.245). This is shown in Table 1. In terms of ethnicity, triple negative breast cancer was found in 56% of African-American and 44% of Caucasians. Non-triple negative breast cancer was found in 48.2% of African-Americans and 51.8% of Caucasians (P-value 0.354) (Table 2).

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Table 1. Comparison of BMI With Estrogen, Progesterone Receptors (ER, PR) and Her2/Neu Protein Expression

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Table 2. Comparison of Ethnicity With Estrogen, Progesterone Receptors (ER, PR) and Her2/Neu Protein Expression

Several studies have explored the relationship between body mass index (BMI) and the incidence of breast cancer [22-24]. Weight gain early on in life has also been associated with a higher incidence of breast cancer later in life [23, 25-35]. Before menopause, female ovaries play a vital role in the production of estrogen whereas in the postmenopausal stage this role is primarily taken over by the adrenal glands [36]. In premenopausal women the higher levels of estrogen results in an increased number of anovulatory menstrual cycles and therefore the higher levels of estrogen here does not lead to a significantly increased incidence of breast cancer [36, 37]. However, in the post-menopausal women with higher body mass index (BMI), higher adiposity generates elevated levels of circulating estrogen which is associated with an increased incidence of breast cancer in these females [36, 37]. Studies have also shown a higher correlation between obesity and estrogen receptor positive (ER+) breast cancers [38]. This correlation is also seen when hormone replacement therapy is used by post-menopausal women [39]. Data collected from several other studies has shown a strong correlation between obesity, higher tumor burden and higher breast cancer grade [10, 40-43] and irrespective of the menopausal status, research has also revealed poorer prognosis with higher mortality [4, 10, 41-48].

In those pre-menopausal women who do develop breast cancer, a higher BMI before diagnosis is associated with a higher mortality rate [3-10], however the association between mortality and weight increase after the diagnosis of breast cancer is not well established [11-17]. Improvement in modern diagnostic tools and therapeutic regimens have resulted in the early detection and improved subsequent management of breast cancers and this general trend is now regarded as the most significant factor in decreasing breast cancer associated mortality [49]. It is because of this reason that millions of female breast cancer survivors are alive today [49]. Besides the improved screening tools and chemotherapy regimens, special focus is also placed on cardiovascular complications which have historically been a major source of death in breast cancer survivors [50].

Body mass index is a simple tool that is often used to stratify weight status and the risk for comorbidities like hyperlipidemia, hypertension, type 2 diabetes, sleep apnea, and certain malignancies including breast cancer [51-53]. BMI is a modifiable risk factor and understanding the relationship between BMI and the aforementioned comorbidities is extremely important. Table 3 below stratifies the BMI index and the associated risk of develop comorbidities [53].

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Table 3. Classification of Weight Status and Risk of Disease

Our retrospect cohort study showed that the proportion of women with higher BMI and triple negative breast cancer was 73.6%. Similarly the proportion of women with higher BMI in the non-triple negative breast cancer population was 86.55%. However, the P-value was measured at 0.245, making the association between body mass index and tumor negative breast cancer to be statistically insignificant. Our findings also showed that in terms of ethnicity, triple negative breast cancer was proportionally more common in African American females (56%) compared to the Caucasian females (44%), as shown in Table 2. However, the P-value was 0.354 making this finding statistically insignificant as well.

Our findings are not in agreement with the data pooled from previous studies which not only established a higher incidence of triple negative breast cancer in African American women compared to their white counterparts, but also showed that the African American females are more likely to present at an advanced stage, higher grade and fared worse with respect to disease free survival and overall survival [54-67]. In African American women the rate of mortality from breast cancer has not only remained higher but the rate of decline has also lagged behind white women [54-65].

There are certain limitations to our research study, least of which is the small sample size. We were only able to assess 84 triple negative breast cancer patients who met our criteria in the IRB approved time period from 2004 to 2008. The small sample size makes it very difficult to deduce any significant conclusions with absolute certainty. This shortcoming can be overcome in the future by pooling data in a larger, multicenter study. Another shortcoming is that we were not able to record menstrual status in our sample size. This could have helped us further investigate the relationship between the incidence of breast cancer and menstrual status in our patient population.

Our retrospect cohort study aimed to investigate the relationship between BMI and breast cancers receptor subtype and ethnicity. We were not able to show any statistically significant association between high BMI with receptor subtype or ethnicity. Our findings are not in agreement with the previously published research; however, this is a retrospective cohort study from one center with a small sample size which greatly limits our ability to deduce any definitive conclusions. In light of these shortcomings, we recommend a future multicenter study with a larger sample size.

Grant Support

None.

Financial Disclosures

No financial help was taken from any internal or external source. This being a retrospect study, no financial support was required.

Competing Interests

None.

1. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010;303(3):235-241.
   doi pubmed
2. Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology. 2007;132(6):2087-2102.
   doi pubmed
3. Zhang S, Folsom AR, Sellers TA, Kushi LH, Potter JD. Better breast cancer survival for postmenopausal women who are less overweight and eat less fat. The Iowa Women's Health Study. Cancer. 1995;76(2):275-283.
   doi
4. Daling JR, Malone KE, Doody DR, Johnson LG, Gralow JR, Porter PL. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer. 2001;92(4):720-729.
   doi
5. Rock CL, Demark-Wahnefried W. Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol. 2002;20(15):3302-3316.
   doi pubmed
6. Chlebowski RT, Aiello E, McTiernan A. Weight loss in breast cancer patient management. J Clin Oncol. 2002;20(4):1128-1143.
   doi pubmed
7. Petrelli JM, Calle EE, Rodriguez C, Thun MJ. Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Causes Control. 2002;13(4):325-332.
   doi pubmed
8. Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, Phillips KA. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(7):1686-1691.
   doi pubmed
9. Whiteman MK, Hillis SD, Curtis KM, McDonald JA, Wingo PA, Marchbanks PA. Body mass and mortality after breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev. 2005;14(8):2009-2014.
   doi pubmed
10. Cleveland RJ, Eng SM, Abrahamson PE, Britton JA, Teitelbaum SL, Neugut AI, Gammon MD. Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev. 2007;16(9):1803-1811.
    doi pubmed
11. Chlebowski RT, Weiner JM, Reynolds R, Luce J, Bulcavage L, Bateman JR. Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy. Breast Cancer Res Treat. 1986;7(1):23-30.
    doi pubmed
12. Goodwin PJ, Panzarella T, Boyd NF. Weight gain in women with localized breast cancer—a descriptive study. Breast Cancer Res Treat. 1988;11(1):59-66.
    doi pubmed
13. Camoriano JK, Loprinzi CL, Ingle JN, Therneau TM, Krook JE, Veeder MH. Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. J Clin Oncol. 1990;8(8):1327-1334.
    pubmed
14. Levine EG, Raczynski JM, Carpenter JT. Weight gain with breast cancer adjuvant treatment. Cancer. 1991;67(7):1954-1959.
    doi
15. Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol. 2005;23(7):1370-1378.
    doi pubmed
16. Caan BJ, Emond JA, Natarajan L, Castillo A, Gunderson EP, Habel L, Jones L, et al. Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer. Breast Cancer Res Treat. 2006;99(1):47-57.
    doi pubmed
17. Caan BJ, Kwan ML, Hartzell G, Castillo A, Slattery ML, Sternfeld B, Weltzien E. Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer. Cancer Causes Control. 2008;19(10):1319-1328.
    doi pubmed
18. van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol. 2000;152(6):514-527.
    doi pubmed
19. Vatten LJ, Kvinnsland S. Prospective study of height, body mass index and risk of breast cancer. Acta Oncol. 1992;31(2):195-200.
    doi
20. Ursin G, Longnecker MP, Haile RW, Greenland S. A meta-analysis of body mass index and risk of premenopausal breast cancer. Epidemiology. 1995;6(2):137-141.
    doi pubmed
21. Michels KB, Terry KL, Willett WC. Longitudinal study on the role of body size in premenopausal breast cancer. Arch Intern Med. 2006;166(21):2395-2402.
    doi pubmed
22. Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron J, Greenberg ER, Willett WC. Body size and risk of breast cancer. Am J Epidemiol. 1997;145(11):1011-1019.
    doi pubmed
23. Trentham-Dietz A, Newcomb PA, Egan KM, Titus-Ernstoff L, Baron JA, Storer BE, Stampfer M, et al. Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control. 2000;11(6):533-542.
    doi pubmed
24. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. JAMA. 2006;296(2):193-201.
    doi pubmed
25. Barnes-Josiah D, Potter JD, Sellers TA, Himes JH. Early body size and subsequent weight gain as predictors of breast cancer incidence (Iowa, United States). Cancer Causes Control. 1995;6(2):112-118.
    doi pubmed
26. Kumar NB, Lyman GH, Allen K, Cox CE, Schapira DV. Timing of weight gain and breast cancer risk. Cancer. 1995;76(2):243-249.
    doi
27. Magnusson C, Baron J, Persson I, Wolk A, Bergstrom R, Trichopoulos D, Adami HO. Body size in different periods of life and breast cancer risk in post-menopausal women. Int J Cancer. 1998;76(1):29-34.
    doi
28. Ballard-Barbash R. Anthropometry and breast cancer. Body size—a moving target. Cancer. 1994;74(3 Suppl):1090-1100.
    doi
29. Li CI, Stanford JL, Daling JR. Anthropometric variables in relation to risk of breast cancer in middle-aged women. Int J Epidemiol. 2000;29(2):208-213.
    doi
30. Enger SM, Ross RK, Paganini-Hill A, Carpenter CL, Bernstein L. Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. Cancer Epidemiol Biomarkers Prev. 2000;9(7):681-687.
    pubmed
31. Friedenreich CM, Courneya KS, Bryant HE. Case-control study of anthropometric measures and breast cancer risk. Int J Cancer. 2002;99(3):445-452.
    doi pubmed
32. Feigelson HS, Jonas CR, Teras LR, Thun MJ, Calle EE. Weight gain, body mass index, hormone replacement therapy, and postmenopausal breast cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2004;13(2):220-224.
    doi pubmed
33. Slattery ML, Sweeney C, Edwards S, Herrick J, Baumgartner K, Wolff R, Murtaugh M, et al. Body size, weight change, fat distribution and breast cancer risk in Hispanic and non-Hispanic white women. Breast Cancer Res Treat. 2007;102(1):85-101.
    doi pubmed
34. Ahn J, Schatzkin A, Lacey JV Jr, Albanes D, Ballard-Barbash R, Adams KF, Kipnis V, et al. Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Intern Med. 2007;167(19):2091-2102.
    doi pubmed
35. Cecchini RS, Costantino JP, Cauley JA, Cronin WM, Wickerham DL, Land SR, Weissfeld JL, et al. Body mass index and the risk for developing invasive breast cancer among high-risk women in NSABP P-1 and STAR breast cancer prevention trials. Cancer Prev Res (Phila). 2012;5(4):583-592.
    doi pubmed
36. Siiteri PK. Adipose tissue as a source of hormones. Am J Clin Nutr. 1987;45(1 Suppl):277-282.
    pubmed
37. Nichols HB, Trentham-Dietz A, Egan KM, Titus-Ernstoff L, Holmes MD, Bersch AJ, Holick CN, et al. Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiol Biomarkers Prev. 2009;18(5):1403-1409.
    doi pubmed
38. Cleary MP, Grossmann ME. Minireview: Obesity and breast cancer: the estrogen connection. Endocrinology. 2009;150(6):2537-2542.
    doi pubmed
39. Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, et al. Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control. 2002;13(8):741-751.
    doi pubmed
40. Maehle BO, Tretli S, Skjaerven R, Thorsen T. Premorbid body weight and its relations to primary tumour diameter in breast cancer patients; its dependence on estrogen and progesteron receptor status. Breast Cancer Res Treat. 2001;68(2):159-169.
    doi pubmed
41. Berclaz G, Li S, Price KN, Coates AS, Castiglione-Gertsch M, Rudenstam CM, Holmberg SB, et al. Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience. Ann Oncol. 2004;15(6):875-884.
    doi pubmed
42. Demirkan B, Alacacioglu A, Yilmaz U. Relation of body mass index (BMI) to disease free (DFS) and distant disease free survivals (DDFS) among Turkish women with operable breast carcinoma. Jpn J Clin Oncol. 2007;37(4):256-265.
    doi pubmed
43. Feigelson HS, Patel AV, Teras LR, Gansler T, Thun MJ, Calle EE. Adult weight gain and histopathologic characteristics of breast cancer among postmenopausal women. Cancer. 2006;107(1):12-21.
    doi pubmed
44. Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 2007;335(7630):1134.
    doi pubmed
45. Barnett JB. The relationship between obesity and breast cancer risk and mortality. Nutr Rev. 2003;61(2):73-76.
    doi pubmed
46. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-1638.
    doi pubmed
47. Barnett GC, Shah M, Redman K, Easton DF, Ponder BA, Pharoah PD. Risk factors for the incidence of breast cancer: do they affect survival from the disease?. J Clin Oncol. 2008;26(20):3310-3316.
    doi pubmed
48. Dal Maso L, Zucchetto A, Talamini R, Serraino D, Stocco CF, Vercelli M, Falcini F, et al. Effect of obesity and other lifestyle factors on mortality in women with breast cancer. Int J Cancer. 2008;123(9):2188-2194.
    doi pubmed
49. Ries LAG, Melbert D, Krapcho M, et al., editors. SEER cancer statistics review, 1975-2004. Bethesda: National Cancer Institute.
50. Heron MP, Hoyert DL, Xu J, Scott C, Tejada-Vera B. Deaths: preliminary data for 2006. National Vital Statistics Reports. 2008;56
51. World Health Organization. Physical status: The use and interpretation of anthropometry. Geneva, Switzerland: World Health Organization 1995. WHO Technical Report Series.
52. “Executive Summary”. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. National Heart, Lung, and Blood Institute. September 1998. xi–xxx.
53. Kushner RF. Chapter 78. Evaluation and Management of Obesity. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
54. Ries LAG, Eisner MP, Kosary CL, et al: Cancer Statistics Review, 1975-2002. Bethesda, MD, National Cancer Institute, 2007.
55. Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007;25(13):1683-1690.
    doi pubmed
56. Chevarley F, White E. Recent trends in breast cancer mortality among white and black US women. Am J Public Health. 1997;87(5):775-781.
    doi
57. Jatoi I, Miller AB. Why is breast-cancer mortality declining?. Lancet Oncol. 2003;4(4):251-254.
    doi
58. Blackman DJ, Masi CM. Racial and ethnic disparities in breast cancer mortality: are we doing enough to address the root causes?. J Clin Oncol. 2006;24(14):2170-2178.
    doi pubmed
59. Jatoi I, Anderson WF, Rao SR, Devesa SS. Breast cancer trends among black and white women in the United States. J Clin Oncol. 2005;23(31):7836-7841.
    doi pubmed
60. Li CI. Racial and ethnic disparities in breast cancer stage, treatment, and survival in the United States. Ethn Dis. 2005;15(2 Suppl 2):S5-9.
    pubmed
61. Sarker M, Jatoi I, Becher H. Racial differences in breast cancer survival in women under age 60. Breast Cancer Res Treat. 2007;106(1):135-141.
    doi pubmed
62. Tammemagi CM, Nerenz D, Neslund-Dudas C, Feldkamp C, Nathanson D. Comorbidity and survival disparities among black and white patients with breast cancer. JAMA. 2005;294(14):1765-1772.
    doi pubmed
63. Field TS, Buist DS, Doubeni C, Enger S, Fouayzi H, Hart G, Korner EJ, et al. Disparities and survival among breast cancer patients. J Natl Cancer Inst Monogr. 2005;(35):88-95.
    doi pubmed
64. Chu KC, Lamar CA, Freeman HP. Racial disparities in breast carcinoma survival rates: seperating factors that affect diagnosis from factors that affect treatment. Cancer. 2003;97(11):2853-2860.
    doi pubmed
65. Vastag B. Breast cancer racial gap examined: no easy answers to explain disparities in survival. JAMA. 2003;290(14):1838-1842.
    doi pubmed
66. Albain K, Unger J, Green K, et al. Outcome of African American on the Southwest Oncology Group (SWOG) breast cancer adjuvant therapy trials. Presented at the 26th Annual San Antionio Breast Conference, San Antonio, TX, December 7-9, 2003.
67. Menashe I, Anderson WF, Jatoi I, Rosenberg PS. Underlying causes of the black-white racial disparity in breast cancer mortality: a population-based analysis. J Natl Cancer Inst. 2009;101(14):993-1000.
    doi pubmed

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