Skip to main content

Advertisement

Log in

The contribution of postmenopausal hormone use cessation to the declining incidence of breast cancer

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

The striking decline in United States breast cancer incidence since 2002 has been widely attributed to a reduction in postmenopausal hormone use, yet very little analysis has been conducted to quantify the contribution of changes in hormone use to the declining trend. We used literature-based estimates of the relative risk and the changing prevalence of hormone use to estimate the impact of hormone use on the decline in breast cancer incidence between 2002 and 2003 among women aged 40–79. For the base case of a 44% decline in hormone use and a relative risk for current use of 1.5, we estimated that 43% of the decline in incidence was attributable to hormone use. By exploring a range of parameter values, we found that high, unlikely values of the relative risk (i.e., ≥ 2.25) and/or the percent decline in hormone use (i.e., ≥ 75%) would be required to account for 100% of the observed decline in breast cancer incidence. We conclude that hormone use is unlikely to account for more than half of the observed decline in breast cancer incidence between 2002 and 2003. Further efforts are needed to quantify the potential contributions of other factors, such as the plateau in screening mammography utilization.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

WHI:

Women’s health initiative

RR:

Relative risk

SEER:

Surveillance Epidemiology and End Results

ER:

Estrogen receptor

References

  1. Ravdin PM, Cronin KA, Howlader N et al (2007) The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med 356(16):1670–1674

    Article  CAS  PubMed  Google Scholar 

  2. Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA (2007) Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst 99(17):1335–1339

    Article  PubMed  Google Scholar 

  3. Kolata G (2006) Reversing trend, big drop is seen in breast cancer. In: The New York Times. 15 December 2006

  4. Jemal A, Ward E, Thun MJ (2007) Recent trends in breast cancer incidence rates by age and tumor characteristics among U.S. women. Breast Cancer Res 9(3):R28

    Article  PubMed  Google Scholar 

  5. Robbins AS, Clarke CA (2007) Re: declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst 99(23):1815; author reply 1816–1817

    Google Scholar 

  6. Harris JR, Lippman ME, Veronesi U, Willett W (1992) Breast cancer (1). N Engl J Med 327(5):319–328

    Article  CAS  PubMed  Google Scholar 

  7. Holford TR, Cronin KA, Mariotto AB, Feuer EJ (2006) Chapter 4: changing patterns in breast cancer incidence trends. J Natl Cancer Inst Monogr 36:19–25

    PubMed  Google Scholar 

  8. Miller BA, Feuer EJ, Hankey BF (1993) Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin 43(1):27–41

    Article  CAS  PubMed  Google Scholar 

  9. Chu KC, Tarone RE, Kessler LG et al (1996) Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 88(21):1571–1579

    Article  CAS  PubMed  Google Scholar 

  10. Altekruse SF, Kosary CL, Krapcho M et al. (2010) SEER cancer statistics review, 1975–2007. National Cancer Institute, Bethesda, MD. http://seer.cancer.gov/csr/1975_2007/, based on November 2009 SEER data submission, posted to the SEER web site

  11. Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52, 705 women with breast cancer and 108, 411 women without breast cancer. Lancet 350(9084):1047–1059

    Article  Google Scholar 

  12. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3):321–333

    Article  CAS  PubMed  Google Scholar 

  13. Haas JS, Kaplan CP, Gerstenberger EP, Kerlikowske K (2004) Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med 140(3):184–188

    PubMed  Google Scholar 

  14. Clarke CA, Glaser SL, Uratsu CS et al (2006) Recent declines in hormone therapy utilization and breast cancer incidence: clinical and population-based evidence. J Clin Oncol 24(33):e49–e50

    Article  PubMed  Google Scholar 

  15. Buist DS, Newton KM, Miglioretti DL et al (2004) Hormone therapy prescribing patterns in the United States. Obstet Gynecol 104(5 Pt 1):1042–1050

    Article  PubMed  Google Scholar 

  16. Hersh AL, Stefanick ML, Stafford RS (2004) National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA 291(1):47–53

    Article  CAS  PubMed  Google Scholar 

  17. Glass AG, Lacey JV Jr, Carreon JD, Hoover RN (2007) Breast cancer incidence, 1980–2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst 99(15):1152–1161

    Article  PubMed  Google Scholar 

  18. Robbins AS, Clarke CA (2007) Regional changes in hormone therapy use and breast cancer incidence in California from 2001 to 2004. J Clin Oncol 25(23):3437–3439

    Article  PubMed  Google Scholar 

  19. Colditz GA (2007) Decline in breast cancer incidence due to removal of promoter: combination estrogen plus progestin. Breast Cancer Res 9(4):108

    Article  PubMed  Google Scholar 

  20. Anderson GL, Limacher M, Assaf AR et al (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291(14):1701–1712

    Article  CAS  PubMed  Google Scholar 

  21. SEER*Stat Database: Incidence—SEER 9 Regs Research Data, Nov 2009 Sub (1973–2007) <Katrina/Rita Population Adjustment>—Linked to County Attributes—Total U.S., 1969–2007 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2010, based on the November 2009 submission (www.seer.cancer.gov)

  22. Beral V (2003) Breast cancer and hormone-replacement therapy in the million women study. Lancet 362(9382):419–427

    Article  CAS  PubMed  Google Scholar 

  23. Standard Populations (Millions) for Age-Adjustment (2007) Available at: http://seer.cancer.gov/stdpopulations/. Accessed Apr 2007

  24. Clarke CA, Glaser SL (2007) Declines in breast cancer after the WHI: apparent impact of hormone therapy. Cancer Causes Control 18(8):847–852

    Article  PubMed  Google Scholar 

  25. Coombs NJ, Cronin KA, Taylor RJ, Freedman AN, Boyages J (2010) The impact of changes in hormone therapy on breast cancer incidence in the US population. Cancer Causes Control 21(1):83–90

    Article  PubMed  Google Scholar 

  26. Colditz GA, Hankinson SE, Hunter DJ et al (1995) The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 332(24):1589–1593

    Article  CAS  PubMed  Google Scholar 

  27. Schairer C, Lubin J, Troisi R et al (2000) Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 283(4):485–491

    Article  CAS  PubMed  Google Scholar 

  28. Kerlikowske K, Miglioretti DL, Ballard-Barbash R et al (2003) Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population. J Clin Oncol 21(23):4314–4321

    Article  CAS  PubMed  Google Scholar 

  29. Li CI, Weiss NS, Stanford JL, Daling JR (2000) Hormone replacement therapy in relation to risk of lobular and ductal breast carcinoma in middle-aged women. Cancer 88(11):2570–2577

    Article  CAS  PubMed  Google Scholar 

  30. Newcomb PA, Titus-Ernstoff L, Egan KM et al (2002) Postmenopausal estrogen and progestin use in relation to breast cancer risk. Cancer Epidemiol Biomarkers Prev 11(7):593–600

    CAS  PubMed  Google Scholar 

  31. Daling JR, Malone KE, Doody DR et al (2002) Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma. Cancer 95(12):2455–2464

    Article  CAS  PubMed  Google Scholar 

  32. Stierer M, Rosen H, Weber R et al (1993) Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. Correlation of histopathology and prognostic factors. Ann Surg 218(1):13–21

    Article  CAS  PubMed  Google Scholar 

  33. Li CI, Daling JR (2007) Changes in breast cancer incidence rates in the United States by histologic subtype and race/ethnicity, 1995 to 2004. Cancer Epidemiol Biomarkers Prev 16(12):2773–2780

    Article  PubMed  Google Scholar 

  34. Longnecker MP, Bernstein L, Paganini-Hill A, Enger SM, Ross RK (1996) Risk factors for in situ breast cancer. Cancer Epidemiol Biomarkers Prev 5(12):961–965

    CAS  PubMed  Google Scholar 

  35. Claus EB, Stowe M, Carter D (2001) Breast carcinoma in situ: risk factors and screening patterns. J Natl Cancer Inst 93(23):1811–1817

    Article  CAS  PubMed  Google Scholar 

  36. Ross RK, Paganini-Hill A, Wan PC, Pike MC (2000) Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst 92(4):328–332

    Article  CAS  PubMed  Google Scholar 

  37. Reeves GK, Beral V, Green J, Gathani T, Bull D (2006) Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis. Lancet Oncol 7(11):910–918

    Article  CAS  PubMed  Google Scholar 

  38. National Center for Health Statistics: Health, United States, 2008 with chartbook

  39. CDC (2007) Use of mammograms among women aged > 40 years—United States, 2000–2005. MMWR 56:49–51

    Google Scholar 

  40. Caan B, Habel L, Quesenberry C, Kushi L, Herrinton L (2008) Re: declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst 100(8):597–598; author reply 599

    Google Scholar 

  41. Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90(18):1371–1388

    Article  CAS  PubMed  Google Scholar 

  42. Feuer EJ (2006) Modeling the impact of adjuvant therapy, screening mammography on U.S. breast cancer mortality between 1975 and 2000: introduction to the problem. J Natl Cancer Inst Monogr 2006(36):2–6

    Google Scholar 

  43. Surveillance Epidemiology and End Results (SEER) Program: SEER*Stat database [released April 2009, based on the November 2008 submission] (www.seer.cancer.gov)

Download references

Acknowledgments

We are grateful to Dr. Polly Newcomb for her advice and support and Dr. Diana Buist for providing access to her published data. This work was supported by the National Institutes of Health (CA067264). Dr. Sprague is supported by a Cancer Prevention Research Fellowship from the Prevent Cancer Foundation and the American Society of Preventive Oncology.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Brian L. Sprague.

Appendix

Appendix

To incorporate elevated risk (compared to never users) among women who quit using hormones after the WHI results, a few simple modifications to the model were made.

For the post-WHI period, Eq. (2) in the main model was replaced by the following relations:

$$ N_{c,a,2003} = P_{{a,{\text{post - WHI}}}} \times N_{t,a,2003} $$
$$ N_{f,a,2003} = (P_{{a,{\text{pre - WHI}}}} - P_{{a,{\text{post - WHI}}}} ) \times N_{t,a,2003}$$
$$ N_{n,a,2003} = (1 - P_{{a,{\text{pre - WHI}}}} ) \times N_{t,a,2003} $$

where N c , N f , and N n are the number of current, former and never users, respectively. Breast cancer incidence among these groups are related to each other by the relative risk (RR):

$$ I_{c,a} = {\text{RR}}_{c} \times I_{n,a} \quad {\text{and}}\quad I_{f,a} = {\text{RR}}_{f} \times I_{n,a} $$

Equation (5) in the main model was then replaced with the following equation for incidence in 2003:

$$ I_{t,a,2003} = {\frac{{I_{c,a} \times P_{{a,{\text{post - WHI}}}} \times N_{t,a,2003} + I_{f,a} \times (P_{{a,{\text{pre - WHI}}}} - P_{{a,{\text{post - WHI}}}} ) \times N_{t,a,2003} + I_{n,a} \times (1 - P_{{a,{\text{pre - WHI}}}} ) \times N_{t,a,2003} }}{{N_{t,a,2003} }}} $$

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sprague, B.L., Trentham-Dietz, A. & Remington, P.L. The contribution of postmenopausal hormone use cessation to the declining incidence of breast cancer. Cancer Causes Control 22, 125–134 (2011). https://doi.org/10.1007/s10552-010-9682-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-010-9682-7

Keywords

Navigation