Skip to main content
SpringerLink
Log in

Premorbid body weight and its relations to primary tumour diameter in breast cancer patients; its dependence on estrogen and progesteron receptor status

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Hormonal mechanisms have been offered as an explanation for the higher frequency of large tumours, lymph node metastases and poorer prognosis in obese breast cancer patients than in lean ones. If hormonal mechanisms are important for these relations, they should probably act more strongly in patients with hormonal receptor positive tumours than in those with negative ones. We have examined if the relations between premorbid body weight or Quetelet's index (weight/height2) and tumour diameter are modified by estrogen receptor alpha (ER) and progesteron receptor (PgR) status. The analyses were based on 1,241 women with unilateral disease treated with modified radical mastectomy living in the geografic area of Haukeland Hospital. Their body weight and height have been measured as a mean 12.5years before presentation of the disease. Body weight and Quetelet's index have been adjusted for age. The relations were studied using linear regression analyses adjusting the effect of body weight with height and mean nuclear area of the tumour cells and adjusting the effect of Quetelet's index for mean nuclear area. The main findings showed that patients with high body weight or Quetelet's index presented more often with PgR positive tumours than lean ones. Quetelet's index was also positively related to ER. These relations were present in patients older than 50 years of age (older). Patients with large tumours (>2.0cm) had significantly higher body weight and Quetelet's index than those with small ones. These differences were significantly present in older patients and in patients with PgR negative and ER negative – PgR negative tumours. Linear regression analyses confirmed that tumour diameter increases with body weight and Quetelet's index. These relations were present in both lymph node groups and in older patients. Stratification according to hormonal receptor status showed these relations to be significant in patients with ER negative, with PgR negative and those with ER negative – PgR negative tumours only. Taking age and hormonal receptor status into consideration simultaneously, both body weight and Quetelet's index were significantly related to tumour diameter in older patients with hormone receptor negative tumours. In conclusion body size was positively related to hormone receptor status and to diameter of the primary tumour. The relation to tumour diameter was present in older patients with hormone receptor negative tumours. Although hormonal mechanisms able to act on the tumour can not be excluded, mechanisms acting independent of hormonal receptors must be considered. Different mechanisms related to body fat cytokines are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abe R, Kumagai N, Kimura M, Hirosaki A, Nakamura T: Biological characteristics of breast cancer in obesity. Tohoku J Exp Med 120: 351-359, 1976

    Google Scholar 

  2. Willett WC, Browne ML, Bain C, Lipnick RJ, Stampfer MJ, Rosner B, Colditz GA, Hennekens CH, Speizer FE: Relative weight and risk of breast cancer among premenopausal women. Am J Epidemiol 122: 731-740, 1985

    Google Scholar 

  3. Daniell HW: Increased lymph node metastases at mastectomy for breast cancer associated with host obesity, cigarette smoking, age, and large tumor size. Cancer 62: 429-435, 1988

    Google Scholar 

  4. Verreault R, Brisson J, DeschÊnes, Naud F: Body weight and prognostic indicators in breast cancer. Modifying effect of estrogen receptors. Am J Epidemiol 129: 260-269, 1989

    Google Scholar 

  5. Tretli S, Haldorsen T, Ottestad L: The effect of pre-morbid height and weight on the survival of breast cancer patients. Br J Cancer 62: 299-303, 1990

    Google Scholar 

  6. Haybittle J, Houghton J, Baum M: Social class and weight as prognostic factors in early breast cancer. Br J Cancer 75: 29-733, 1997

    Google Scholar 

  7. De Ward F, Cornelis JP, Aoki K, Yoshida M: Breast cancer incidence according to weight and height in two cities of the Netherlands and in Aichi prefecture, Japan. Cancer 40: 1269-1275, 1977

    Google Scholar 

  8. Greenberg ER, Vessey MP, McPherson K, Doll R, Yeates D: Body size and survival in premenopausal breast cancer. Br J Cancer 51: 691-697, 1985

    Google Scholar 

  9. Eberlein T, Simon R, Fisher S, Lippman ME: Height, weight, and risk of breast cancer relapse. Br Cancer Res Treat 5: 81-86, 1985

    Google Scholar 

  10. Schapira DV, Kumar NB, Lyman GH, Cox CE: Obesity and body fat distribution and breast cancer prognosis. Cancer 67: 523-528, 1991

    Google Scholar 

  11. Senie RT, Rosen PP, Rhodes P, Lesser ML, Kinne DW: Obesity at diagnosis of breast carcinoma influences duration of disease-free survival. Ann Intern Med 116: 26-32, 1992

    Google Scholar 

  12. Tretli S: Height and weight in relation to breast cancer morbidity and mortality. A prospective study of 570, 000 women in Norway. Int J Cancer 44: 23-30, 1989

    Google Scholar 

  13. Boyd NF, Campbell JE, Germanson T, Thomson DB, Sutherland DJ, Meakin JW: Body weight and prognosis in breast cancer. JNCI 67: 785-789, 1981

    Google Scholar 

  14. Tartter PI, Papatestas AE, Ioannovich J, Mulvihill MN, Lesnick G, Aufses AH: Cholesterol and obesity as prognostic factors in breast cancer. Cancer 47: 2222-2227, 1981

    Google Scholar 

  15. Hebert JR, Augustine A, Barone J, Kabat GC, Kinne DW, Wynder EL: Weight, height and body mass index in the prognosis of breast cancer: early results of a prospective study. Int J Cancer 42: 315-318, 1988

    Google Scholar 

  16. Kyogoku S, Hirohata T, Takeshita S, Nomura Y, Shigematsu T, Horie A: Survival of breast-cancer patients and body size indicators. Int J Cancer 46: 824-831, 1990

    Google Scholar 

  17. Vatten LJ, Foss OP, Kvinnsland S: Overall survival of breast cancer patients in relation to preclinically determined total serum cholesterol, body mass index, height and cigarette smoking: a population-based study. Eur J Cancer 27: 641-646, 1991

    Google Scholar 

  18. Cleland WH, Mendelson CR, Simpson ER: Effects of aging and obesity on aromatase activity of human adipose cells. J Clin Endocrin Metab 60(1): 174-177, 1985

    Google Scholar 

  19. Enriori CL, Orsini W, Cremona MdC, Etkin AE, Cardillo LR, Reforzo-Membrives J: Decrease of circulating level of SHBG in postmenopausal obese women as a risk factor in breast cancer: reversible effect of weight loss. Gynecol Oncol 23: 77-86, 1986

    Google Scholar 

  20. Reed MJ, Purohit A: Breast cancer and the role of cytokines in regulating estrogen synthesis: an emerging hypothesis. Endocrine Reviews 18(5): 701-715, 1997

    Google Scholar 

  21. MÆhle BO, Tretli S: Pre-morbid body-mass-index in breast cancer: reversed effect on survival in hormone receptor negative patients. Breast Cancer Res Treat 41: 123-130, 1996

    Google Scholar 

  22. MÆhle BO, SkjÆrven R: Prediction of prognosis in axillary lymph node positive breast cancer patients: a statistical study. Br J Surg 71: 459-462, 1984

    Google Scholar 

  23. MÆhle BO, Thoresen S, SkjÆrven R, Hartveit F: Mean nuclear area and histological grade of axillary-node tumour in breast cancer, related to prognosis. Br J Cancer 46: 95-100, 1982

    Google Scholar 

  24. Thorsen T: Occupied and unoccupied oestradiol receptor in human breast tumours: relation to oestradiol and progesterone cytosol receptors. J Steroid Biochem 10: 661-668, 1979

    Google Scholar 

  25. Hermanek P, Hutter RVP, Sobin LH, Wittekind Ch: International Union Against Cancer (UICC): TNM Atlas, 4th edition. Springer, 1997, p 123-120

  26. EGRET. Reference Manual. 4th rev. Seattle, WA, Statistics and Epidemiology Research Cooperation, 1993, pp 80-81

    Google Scholar 

  27. Gapstur SM, Potter JD, Drinkard C and Folsom AR: Synergistic effect between alcohol and estrogen replacement therapy on risk breast cancer differs by estrogen/progesterone receptor status in the Iowa women's health study. Cancer Epidemiol Biomarkers Prevent 4: 313-318, 1995

    Google Scholar 

  28. Katz EB, Boylan ES: Stimulatory effect of high polyunsaturated fat diet on lung metastases from the 13762 mammary adenocarcinoma in female retired breeder rats. JNCI 79: 351-358, 1987

    Google Scholar 

  29. Thoresen S, Tangen M, Hartveit F: Oestrogen and progesterone receptor content and the distribution of histological grade in breast cancer. Br Cancer Res Treat 2: 251-255, 1982

    Google Scholar 

  30. Thor AD, Moore DH II, Edgerton SM, Kawasaki ES, Reihsaus E, Lynch HT, Marcus, JN, Schwartz L, Chen LC, Mayall BH, Smith HS: Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84: 845-855, 1992

    Google Scholar 

  31. Rudolph P, Olsson H, Bonatz G, Ratjen V, Bolte H, Baldetorp B, Ferno M, Parwaresch R, Alm P: Correlation between p53, c-erbB-2, and topoisomerase II alpha expression, DNA ploidy, hormonal receptor status and proliferation in 356 nodenegative breast carcinomas: prognostic implications. J Pathol 187: 207-16, 1999

    Google Scholar 

  32. McLeay WR, Horsfall DJ, Seshadri R, Morrison DA, Saccone GT: Epidermal growth factor receptor in breast cancer: storage conditions affecting measurement, and relationship to steroid receptors. Breast Cancer Res Treat 22: 141-51, 1992

    Google Scholar 

  33. Koscielny S, Terrier P, Daver A, Wafflart J, Goussard J, Ricolleau G, Delvincourt C, Delarue JC: Quantitative determination of c-erbB-2 in human breast tumours: potential prognostic significance of low values. Eur J Cancer 34: 476-481, 1998

    Google Scholar 

  34. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P: Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269: 546-549, 1995

    Google Scholar 

  35. Pelleymounter MA, Cullen, MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540-543, 1995

    Google Scholar 

  36. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley, SK, Friedman, JM: Weightreducing effects of the plasma prote in encoded by the obese gene. Science 269: 543-546, 1995

    Google Scholar 

  37. Kern, PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB: The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 95: 2111-2119, 1995

    Google Scholar 

  38. Eriksson P, Reynisdottir S, Lonnqvist F, Stemme, V, Hamsten A, and Arner P: Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 41: 65-71, 1998

    Google Scholar 

  39. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro J: Serum immunoreactive-lept in concentrations in normal-weight and obese humans [see comments]. N Engl J Med 334: 292-295, 1996

    Google Scholar 

  40. Gregoire Nyomba BL, Johnson M, Berard L, Murphy, LJ: Relationship between serum leptin and the insulin-like growth factor-I system in humans. Metabolism 48: 840-844, 1999

    Google Scholar 

  41. Bouloumie A, Drexler HC, Lafontan M, Busse R: Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 83: 1059-1066, 1998

    Google Scholar 

  42. Loskutoff DJ, Samad F: The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 18: 1-6, 1998

    Google Scholar 

  43. Holst-Hansen C, Johannessen B, Hoyer-Hansen G, Romer J, Ellis V, Brunner N: Urokinase-type plasminogen activation in three human breast cancer cell lines correlates with their in vitro invasiveness. Clin Exp Metastasis 14: 297-307, 1996

    Google Scholar 

  44. Holst-Hansen C, Hamers MJ, Johannessen BE, Brunner N, Stephens RW: Soluble urokinase receptor released from human carcinoma cells: a plasma parameter for xenograft tumour studies. Br J Cancer 81: 203-211, 1999

    Google Scholar 

  45. Samad F, Yamamoto K, Loskutoff DJ: Distribution and regulation of plasminogen activator inhibitor-1 in murine adipose tissue in vivo. Induction by tumor necrosis factor-alpha and lipopolysaccharide. J Clin Invest 97: 37-46, 1996.

    Google Scholar 

  46. Kirchgessner TG, Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS: Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes. J Clin Invest 100: 2777-2782, 1997

    Google Scholar 

  47. Magoffin DA, Weitsman SR, Aagarwal SK, and Jakimiuk AJ: Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. Ginekol Pol 70: 1-7, 1999

    Google Scholar 

  48. Giuffrida D, Lupo L, La Porta GA, La Rosa GL, Padova G, Foti E, Marchese V, Belfiore A: Relation between steroid receptor status and body weight in breast cancer patients. Eur J Cancer 28: 112-115, 1992.

    Google Scholar 

  49. Honda H, Ohi Y, Umekita Y, Takasaki T, Kuriwaki K, Ohyabu I, Yoshioka T, Yoshida A, Taguchi S, Ninomiya K, Akiba S, Nomura S, Sagara Y, Yoshida H: Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history. Pathol Int 49: 198-202, 1999

    Google Scholar 

  50. van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, Marshall JR, Miller AB, Rohan T, Smith-Warner SA, Speizer FE, Willett WC, Wolk A, Hunter DJ: Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152: 514-527, 2000

    Google Scholar 

  51. Ursin G, Longnecker MP, Haile RW, Greenland S: A metaanalysis of body mass index and risk of premenopausal breast cancer. Epidemiology 6: 137-141, 1995

    Google Scholar 

  52. Donegan WL, Hartz AJ, Rimm AA: The association of body weight with recurrent cancer of the breast. Cancer 41: 1590-1594, 1978

    Google Scholar 

  53. Newman SC, Miller AB, Howe GR: A study of the effect of weight and dietary fat on breast cancer survival time. Am J Epidemiol 123(5): 767-774, 1986

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Gade Institute, Department of Pathology, Bergen, Norway

    Bjørn Ove Mæhle

  2. The Cancer Registry of Norway, Institute of Epidemiological Cancer Research, Montebello, Oslo, Norway

    Steinar Tretli

  3. Section for Medical Informatics and Statistics, Bergen, Norway

    Rolv Skjærven

  4. The Hormone Laboratory, University of Bergen, Haukeland Hospital, Bergen, Norway

    Thor Thorsen

Authors
  1. Bjørn Ove Mæhle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steinar Tretli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rolv Skjærven
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thor Thorsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ove Mæhle, B., Tretli, S., Skjærven, R. et al. 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 68, 159–169 (2001). https://doi.org/10.1023/A:1011977118921

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1011977118921

Search

Navigation