Advertisement

Breast Cancer Research and Treatment

, Volume 131, Issue 3, pp 925–931 | Cite as

Endocrine therapy in obese patients with primary breast cancer: another piece of evidence in an unfinished puzzle

  • R. WoltersEmail author
  • L. Schwentner
  • A. Regierer
  • M. Wischnewsky
  • R. Kreienberg
  • A. Wöckel
Clinical trial

Abstract

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15–1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03–1.65)). In hormone-receptor-negative (HR−) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80–1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24–2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82–2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63–2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29–1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.

Keywords

Breast cancer Obesity Endocrine therapy Aromatase inhibitor Tamoxifen Menopausal status 

Notes

Acknowledgments

The study was supported by grants of the German Ministry of Education and Research (BMBF).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, Manson J, Margolis KL, Muti PC, Stefanick ML, McTiernan A (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Cause Control 13(8):741–751CrossRefGoogle Scholar
  2. 2.
    Reeves GK, Pirie K, Beral V, Green J, Spencer E, Bull D, Million Women Study Collaboration (2007) Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Br Med J 335(7630):1134CrossRefGoogle Scholar
  3. 3.
    Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, Phillips KA (2005) Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomark 14(7):1686–1691CrossRefGoogle Scholar
  4. 4.
    Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123:627–635PubMedCrossRefGoogle Scholar
  5. 5.
    Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476PubMedCrossRefGoogle Scholar
  6. 6.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638PubMedCrossRefGoogle Scholar
  7. 7.
    Whiteman MK, Hillis SD, Curtis KM, McDonald JA, Wingo PA, Marchbanks PA (2005) Body mass and mortality after breast cancer diagnosis. Cancer Epidemiol Biomark 14(8):2009–2014CrossRefGoogle Scholar
  8. 8.
    Majed B, Moreau T, Senouci K, Salmon RJ, Fourquet A, Asselain B (2008) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat 111(2):329–342PubMedCrossRefGoogle Scholar
  9. 9.
    Petrelli JM, Calle EE, Rodriguez C, Thun MJ (2002) Body mass index, height, and postmenopausal breast cancer mortality in a prospective cohort of US women. Cancer Cause Control 13(4):325–332CrossRefGoogle Scholar
  10. 10.
    Ewertz M, Jensen MB, Gunnarsdóttir KÁ, Højris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S (2011) Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29(1):25–31PubMedCrossRefGoogle Scholar
  11. 11.
  12. 12.
    Sestak I, Distler W, Forbes JF, Dowsett M, Howell A, Cuzick J (2010) Effect of body mass index on recurrences in tamoxifen and anastrozole treated women: an exploratory analysis from the ATAC trial. J Clin Oncol 28(21):3411–3415PubMedCrossRefGoogle Scholar
  13. 13.
    Pfeiler G, Stöger H, Fesl C, Singer C, Seifert M, Jakesz R, Dubsky P, Samonigg H, Greil R, Menzel C, Heck D, Gnant M on behalf of the ABCSG (2010) Impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal breast cancer patients—an analysis of the ABCSG 6 and 6a trial. http://www.abstracts2view.com/sabcs10/viewp.php?nu=PD09-05
  14. 14.
    Pfeiler G, Königsberg R, Fesl C, Mlineritsch B, Stoeger H, Singer CF, Pöstlberger S, Steger GG, Seifert M, Dubsky P, Taucher S, Samonigg H, Bjelic-Radisic V, Greil R, Marth C, Gnant M (2011) Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol 29:2653–2659Google Scholar
  15. 15.
    Goodwin PJ, Pritchard KI (2010) Obesity and hormone therapy in breast cancer: an unfinished puzzle. J Clin Oncol 28(21):3405–3407PubMedCrossRefGoogle Scholar
  16. 16.
    Wöckel A, Varga D, Atassi Z, Kurzeder C, Wolters R, Wischnewsky M, Wulff C, Kreienberg R (2010) Impact of guideline conformity on breast cancer therapy: results of a 13-year retrospective cohort study. Onkologie 33(1–2):21–28PubMedGoogle Scholar
  17. 17.
    Hancke K, Denkinger MD, König J, Kurzeder C, Wöckel A, Herr D, Blettner M, Kreienberg R (2010) Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study. Ann Oncol 21(4):748–753PubMedCrossRefGoogle Scholar
  18. 18.
    Wöckel A, Kurzeder C, Geyer V, Novopashenny I, Wolters R, Wischnewsky M, Kreienberg R, Varga D (2010) Effects of guideline adherence in primary breast cancer—a 5-year multi-center cohort study of 3976 patients. Breast 19(2):120–127PubMedCrossRefGoogle Scholar
  19. 19.
    Regierer AC, Wolters R, Kurzeder C, Wöckel A, Novopashenny I, Possinger K, Wischnewsky MB, Kreienberg R (2011) High estrogen receptor expression in early breast cancer: chemotherapy needed to improve RFS? Breast Cancer Res Treat. doi: 10.1007/s1054901013349
  20. 20.
    Varga D, Wischnewsky M, Atassi Z, Wolters R, Geyer V, Strunz K, Kreienberg R, Woeckel A (2010) Does guideline-adherent therapy improve the outcome for early-onset breast cancer patients? Oncology 78(3–4):189–195PubMedCrossRefGoogle Scholar
  21. 21.
    Maehle BO, Tretli S, Skjaerven R, Thorsen T (2001) Premorbid body weight and its relation to primary tumour diameter in breast cancer patients: its dependence on estrogen and progesterone receptor status. Breast Cancer Res Treat 68:159–169PubMedCrossRefGoogle Scholar
  22. 22.
    Berclaz G, Li S, Price KN, Coates AS, Castiglinone-Gertsch M, Rudenstam CM, Holmberg SB, Lindtner J, Erien D, Collins J, Snyder R, Thürlimann B, Fey MF, Mendiola C, Werner ID, Simoncini E, Crivellari D, Gelber RD, Goldhirsch A, International Breast Cancer Study Group (2004) Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience. Ann Oncol 15:875–884PubMedCrossRefGoogle Scholar
  23. 23.
    Cleveland RJ, Eng SM, Abrahamson PE, Britton JA, Teitelbaum SL, Neugut AI, Gammon MD (2007) Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomark Prev 16:1803–1811CrossRefGoogle Scholar
  24. 24.
    Feigelson HS, Patel AV, Teras LR, Gansler TS, Thun MJ, Calle EE (2006) Adult weight gain and histopathologic characteristics of breast cancer among postmenopausal women. Cancer 1107:12–21CrossRefGoogle Scholar
  25. 25.
    Schmid P, Possinger K, Bohm R, Chaudri V, Verbeek V, Grosse Y, Luftner D, Petrides P, Sezer O, Wischnewsky M (2000) Body mass index as predictive parameter for response and time to progression (TTP) in advanced breast cancer patients treated with letrozole or megestrol acetate. Proc Am Soc Clin Oncol 19:2000 (abstr 398)Google Scholar
  26. 26.
    Michaud LB, Buzdar AU, Rubin S, Steinberg M, Yin H, Aaronson L, Nabholtz JM (2002) The efficacy of anastrozole is not dependent upon body mass index (BMI) in postmenopausal women with advanced breast cancer (BC). Proc Am Soc Clin Oncol 21:2002 (abstr 219)Google Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • R. Wolters
    • 1
    Email author
  • L. Schwentner
    • 2
  • A. Regierer
    • 3
  • M. Wischnewsky
    • 1
  • R. Kreienberg
    • 2
  • A. Wöckel
    • 2
  1. 1.Department of Mathematics and Computer ScienceUniversity BremenBremenGermany
  2. 2.Department of Gynaecology and ObstetricsUniversity Hospital UlmUlmGermany
  3. 3.Department of Oncology and HaematologyCharité Universitätsmedizin Berlin BerlinGermany

Personalised recommendations