Horm Metab Res 2004; 36(5): 336-340
DOI: 10.1055/s-2004-814490
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Leptin Expression in Breast Nipple Aspirate Fluid (NAF) and Serum is Influenced by Body Mass Index (BMI) but not by the Presence of Breast Cancer

E.  R.  Sauter1 , C.  Garofalo2 , J.  Hewett1 , J.  E.  Hewett1 , C.  Morelli2 , E.  Surmacz2
  • 1Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO
  • 2Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
Further Information

Publication History

Received 8 October 2003

Accepted after Revision 24 January 2004

Publication Date:
24 May 2004 (online)

Abstract

While obesity is a known risk factor for postmenopausal breast cancer, the molecular mechanisms involved are unclear. Systemic levels of leptin, the product of the ob (obesity) gene, are increased in obese individuals (body mass index, BMI, over 25) and are higher in women than men. Leptin has been found to stimulate the growth of breast cancer cells in vitro. Our goal was to determine whether leptin was 1) present in nipple aspirate fluid (NAF), and 2) whether NAF leptin levels were associated with a) levels in serum, b) obesity, and c) breast cancer. We collected and evaluated NAF specimens from 83 subjects and serum specimens from 49 subjects. NAF leptin was detectable in 16/41 (39 %) of premenopausal and 21/42 (50 %) postmenopausal subjects. NAF leptin was significantly lower (p = 0.042) in premenopausal than postmenopausal women with a BMI < 25, but not in those with a higher BMI. NAF leptin was significantly associated with BMI in premenopausal (p = 0.011) but not in postmenopausal women. Serum leptin was associated with BMI in both premenopausal and postmenopausal women (p = 0.0001 for both). NAF and serum leptin were associated in premenopausal (p = 0.02) but not postmenopausal women. Neither NAF nor serum leptin was associated with premenopausal or postmenopausal breast cancer. Our findings include that 1) leptin is present in the breast and detectable in a subset of NAF samples, 2) NAF leptin in premenopausal but not postmenopausal women parallels serum leptin levels, and 3) neither NAF nor serum levels of leptin were associated with premenopausal or postmenopausal breast cancer.

References

  • 1 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.  Nature. 1998;  395 763-770
  • 2 Wauters M, Considine R V, Van Gaal L F. Human leptin: from an adipocyte hormone to an endocrine mediator.  Eur J Endocrinol. 2000;  143 293-311
  • 3 Hube F, Lietz U, Igel M, Jensen P B, Tornqvist H, Joost H G. et al . Difference in leptin mRNA levels between omental and subcutaneous abdominal adipose tissue from obese humans.  Horm Metab Res. 1996;  28 690-693
  • 4 Smith-Kirwin S M, O’Connor D M, de Johnston J, Lancey E D, Hassink S G, Funanage V L. Leptin expression in human mammary epithelial cells and breast milk.  J Clin Endocrinol Metab. 1998;  83 1810-1813
  • 5 Uysal F K, Onal E E, Aral Y Z, Adam B, Dilmen U, Ardicolu Y. Breast milk leptin: its relationship to maternal and infant adiposity.  Clin Nutr. 2002;  21 157-160
  • 6 Neville M C, McFadden T B, Forsyth I. Hormonal regulation of mammary differentiation and milk secretion.  J Mammary Gland Biol Neoplasia. 2002;  7 49-66
  • 7 Dieudonne M N, Machinal-Quelin F, Serazin-Leroy V, Leneveu M C, Pecquery R, Giudicelli Y. Leptin mediates a proliferative response in human MCF7 breast cancer cells.  Biochem Biophys Res Commun. 2002;  293 622-628
  • 8 Laud K, Gourdou I, Pessemesse L, Peyrat J P, Djiane J. Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line.  Mol Cell Endocrinol. 2002;  188 219-226
  • 9 Tessitore L, Vizio B, Jenkins O, de Stefano I, Ritossa C, Argiles J M. et al . Leptin expression in colorectal and breast cancer patients.  Int J Mol Med. 2000;  5 421-426
  • 10 Petridou E, Papadiamantis Y, Markopoulos C, Spanos E, Dessypris N, Trichopoulos D. Leptin and insulin growth factor I in relation to breast cancer (Greece).  Cancer Causes Control. 2000;  11 383-388
  • 11 Mantzoros C S, Bolhke K, Moschos S, Cramer D W. Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls.  Int J Cancer. 1999;  80 523-526
  • 12 Harvard Health Letter 2001. 
  • 13 Sauter E R, Ross E, Daly M, Klein-Szanto A, Engstrom P F, Sorling A. et al . Nipple aspirate fluid: a promising non-invasive method to identify cellular markers of breast cancer risk.  Br J Cancer. 1997;  76 494-501
  • 14 Sauter E R, Ehya H, Babb J, Diamandis E, Daly M, Klein-Szanto A. et al . Biological markers of risk in nipple aspirate fluid are associated with residual cancer and tumour size.  Br J Cancer. 1999;  81 1222-1227
  • 15 Sauter E R, Daly M, Linahan K, Ehya H, Engstrom P F, Bonney G. et al . Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk.  Cancer Epidemiol Biomarkers Prev. 1996;  5 967-970
  • 16 Friedenreich C M. Review of anthropometric factors and breast cancer risk.  Eur J Cancer Prev. 2001;  10 15-32
  • 17 Considine R V, Sinha M K, Heiman M L, Kriauciunas A, Stephens T W, Nyce M R. et al . Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med. 1996;  334 292-295
  • 18 Di Carlo C, Tommaselli G A, Nappi C. Effects of sex steroid hormones and menopause on serum leptin concentrations.  Gynecol Endocrinol. 2002;  16 479-491
  • 19 Hileman S M, Tornoe J, Flier J S, Bjorbaek C. Transcellular transport of leptin by the short leptin receptor isoform ObRa in Madin-Darby Canine Kidney cells.  Endocrinology. 2000;  141 1955-1961
  • 20 Chan J L, Bluher S, Yiannakouris N, Suchard M A, Kratzsch J, Mantzoros C S. Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans.  Diabetes. 2002;  51 2105-2112
  • 21 Duggal P S, Weitsman S R, Magoffin D A, Norman R J. Expression of the long (OB-RB) and short (OB-RA) forms of the leptin receptor throughout the oestrous cycle in the mature rat ovary.  Reproduction. 2002;  123 899-905
  • 22 O’Brien S N, Welter B H, Price T M. Presence of leptin in breast cell lines and breast tumors.  Biochem Biophys Res Commun. 1999;  259 695-698
  • 23 Hileman S M, Pierroz D D, Masuzaki H, Bjorbaek C, El-Haschimi K, Banks W A. et al . Characterizaton of short isoforms of the leptin receptor in rat cerebral microvessels and of brain uptake of leptin in mouse models of obesity.  Endocrinology. 2002;  143 775-783

E. R. Sauter

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