Skip to main content

Advertisement

SpringerLink
Log in

Elevated risks of subsequent endometrial cancer development among breast cancer survivors with different hormone receptor status: a SEER analysis

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

Abstract

Estrogen receptor (ER)-positive breast cancer patients treated with tamoxifen are known to have an elevated risk of subsequent endometrial cancer. However, it is unclear if ER-negative patients also have a higher risk of endometrial cancer. This population-based study aims to evaluate whether breast cancer patients with distinctive ER and PR status possess differential risks in developing delayed endometrial malignancy. Data were obtained from the Surveillance, Epidemiology, and End Results program (1992–2009). Standardized incidence ratio (SIR) was calculated as the observed cases of endometrial cancers among breast cancer survivors compared with the expected cases in the general population. Data were stratified by latency periods, race, age, and calendar year of breast cancer diagnosis. We identified 2044 patients who developed a second primary endometrial cancer among 289,933 breast cancer survivors. The overall SIRs for subsequent endometrial cancers were increased in all of the four subtypes (ER+PR+, ER+PR−, ER−PR+, and ER−PR−) of breast cancer. SIR was increased for all latency periods except for the initial 6–11 months after breast cancer diagnosis. Stratifying by age of diagnosis, elevated SIRs in all ER/PR groups were statistically significant among patients diagnosed with breast cancer after the age of 40. Demographically, non-Hispanic whites had increased SIRs in all subtypes of breast cancer, while Hispanic whites had no statistically elevated SIRs. Here we showed that patients with invasive breast cancer have a higher risk of developing subsequent endometrial cancer regardless of ER or PR status. The increased risk among hormone receptor-negative breast cancer survivors raises concerns whether common etiological factors among these breast cancer subtypes increase the susceptibility to develop endometrial cancer. Lower threshold for routine endometrial cancer surveillance may be warranted.

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

Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

SEER:

Surveillance, epidemiology, and end results

SIRs:

Standardized incidence ratios

CI:

Confidence interval

RR:

Relative ratio

EBCTCG:

Early Breast Cancer Trialists’ Collaborative Group

CIA:

Chemotherapy-induced amenorrhea

BMI:

Body mass index

References

  1. Howlader N NA, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). (2013) SEER Cancer Statistics Review, 1975–2010. National Cancer Institute, Bethesda. http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, April 2013

  2. Hayat MJ, Howlader N, Reichman ME, Edwards BK (2007) Cancer statistics, trends, and multiple primary cancer analyses from the surveillance, epidemiology, and end results (SEER) program. Oncologist 12(1):20–37. doi:10.1634/theoncologist.12-1-20

    Article  PubMed  Google Scholar 

  3. Curtis RE, Boice JD Jr, Shriner DA, Hankey BF, Fraumeni JF Jr (1996) Second cancers after adjuvant tamoxifen therapy for breast cancer. J Natl Cancer Inst 88(12):832–834

    Article  CAS  PubMed  Google Scholar 

  4. van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrere CH, Otter R, Schouten LJ, Damhuis RA, Bontenbal M, Diepenhorst FW et al (1994) Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 343(8895):448–452

    Article  PubMed  Google Scholar 

  5. Bernstein L, Deapen D, Cerhan JR, Schwartz SM, Liff J, McGann-Maloney E, Perlman JA, Ford L (1999) Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 91(19):1654–1662

    Article  CAS  PubMed  Google Scholar 

  6. Chen JY, Kuo SJ, Liaw YP, Avital I, Stojadinovic A, Man YG, Mannion C, Wang J, Chou MC, Tsai HD, Chen ST, Hsiao YH (2014) Endometrial cancer incidence in breast cancer patients correlating with age and duration of tamoxifen use: a population based study. J Cancer 5(2):151–155. doi:10.7150/jca.8412

    Article  PubMed Central  PubMed  Google Scholar 

  7. Schonfeld SJ, Berrington de Gonzalez A, Visvanathan K, Pfeiffer RM, Anderson WF (2013) Declining second primary ovarian cancer after first primary breast cancer. J Clin Oncol 31(6):738–743. doi:10.1200/JCO.2012.43.2757

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kang HJ, Kim SW, Kim HJ, Ahn SJ, Bae JY, Park SK, Kang D, Hirvonen A, Choe KJ, Noh DY (2002) Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk. Cancer Lett 178(2):175–180

    Article  CAS  PubMed  Google Scholar 

  9. Cui X, Schiff R, Arpino G, Osborne CK, Lee AV (2005) Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol 23(30):7721–7735

    Article  CAS  PubMed  Google Scholar 

  10. Rakha EA, El-Sayed ME, Green AR, Paish EC, Powe DG, Gee J, Nicholson RI, Lee AH, Robertson JF, Ellis IO (2007) Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol 25(30):4772–4778

    Article  PubMed  Google Scholar 

  11. Liu S, Chia SK, Mehl E, Leung S, Rajput A, Cheang MC, Nielsen TO (2010) Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients. Breast Cancer Res Treat 119(1):53–61. doi:10.1007/s10549-009-0318-0

    Article  CAS  PubMed  Google Scholar 

  12. Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR (2005) Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5993 breast cancers. Am J Clin Pathol 123(1):21–27

    Article  PubMed  Google Scholar 

  13. De Maeyer L, Van Limbergen E, De Nys K, Moerman P, Pochet N, Hendrickx W, Wildiers H, Paridaens R, Smeets A, Christiaens MR, Vergote I, Leunen K, Amant F, Neven P (2008) Does estrogen receptor negative/progesterone receptor positive breast carcinoma exist? J Clin Oncol 26(2):335–336. doi:10.1200/JCO.2007.14.8411 author reply 336–338

    Article  PubMed  Google Scholar 

  14. Kiani J, Khan A, Khawar H, Shuaib F, Pervez S (2006) Estrogen receptor alpha-negative and progesterone receptor-positive breast cancer: lab error or real entity? Pathol Oncol Res 12(4):223–227 PAOR.2006.12.4.0223

    Article  PubMed  Google Scholar 

  15. Sherman ME, Devesa SS (2003) Analysis of racial differences in incidence, survival, and mortality for malignant tumors of the uterine corpus. Cancer 98(1):176–186. doi:10.1002/cncr.11484

    Article  PubMed  Google Scholar 

  16. Ngo C, Brugier C, Plancher C, de la Rochefordiere A, Alran S, Feron JG, Malhaire C, Scholl S, Sastre X, Rouzier R, Fourchotte V (2014) Clinico-pathology and prognosis of endometrial cancer in patients previously treated for breast cancer, with or without tamoxifen: a comparative study in 363 patients. Eur J Surg Oncol 40(10):1237–1244. doi:10.1016/j.ejso.2014.05.007

    Article  CAS  PubMed  Google Scholar 

  17. Swerdlow AJ, Jones ME (2005) Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study. J Natl Cancer Inst 97(5):375–384

    Article  CAS  PubMed  Google Scholar 

  18. Thompson D, Easton DF (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94(18):1358–1365

    Article  CAS  PubMed  Google Scholar 

  19. Segev Y, Iqbal J, Lubinski J, Gronwald J, Lynch HT, Moller P, Ghadirian P, Rosen B, Tung N, Kim-Sing C, Foulkes WD, Neuhausen SL, Senter L, Singer CF, Karlan B, Ping S, Narod SA (2013) The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: an international prospective cohort study. Gynecol Oncol 130(1):127–131. doi:10.1016/j.ygyno.2013.03.027

    Article  CAS  PubMed  Google Scholar 

  20. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578. doi:10.1016/S0140-6736(08)60269-X

    Article  PubMed  Google Scholar 

  21. Abdel-Maksoud MF, Risendal BC, Slattery ML, Giuliano AR, Baumgartner KB, Byers TE (2012) Behavioral risk factors and their relationship to tumor characteristics in Hispanic and non-Hispanic white long-term breast cancer survivors. Breast Cancer Res Treat 131(1):169–176. doi:10.1007/s10549-011-1705-x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Fournier A, Dossus L, Mesrine S, Vilier A, Boutron-Ruault MC, Clavel-Chapelon F, Chabbert-Buffet N (2014) Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992–2008. Am J Epidemiol 180(5):508–517. doi:10.1093/aje/kwu146

    Article  PubMed  Google Scholar 

  23. Burke WM, Orr J, Leitao M, Salom E, Gehrig P, Olawaiye AB, Brewer M, Boruta D, Villella J, Herzog T, Abu Shahin F (2014) Endometrial cancer: a review and current management strategies: part I. Gynecol Oncol 134(2):385–392. doi:10.1016/j.ygyno.2014.05.018

    Article  PubMed  Google Scholar 

  24. Anderson KN, Schwab RB, Martinez ME (2014) Reproductive risk factors and breast cancer subtypes: a review of the literature. Breast Cancer Res Treat 144(1):1–10. doi:10.1007/s10549-014-2852-7

    Article  PubMed Central  PubMed  Google Scholar 

  25. Schaapveld M, Visser O, Louwman MJ, de Vries EG, Willemse PH, Otter R, van der Graaf WT, Coebergh JW, van Leeuwen FE (2008) Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch population-based study. J Clin Oncol 26(8):1239–1246. doi:10.1200/JCO.2007.11.9081

    Article  PubMed  Google Scholar 

  26. Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378(9793):771–784. doi:10.1016/S0140-6736(11)60993-8

    Article  CAS  PubMed  Google Scholar 

  27. Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362(22):2053–2065. doi:10.1056/NEJMoa0909638

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Swain SM, Land SR, Ritter MW, Costantino JP, Cecchini RS, Mamounas EP, Wolmark N, Ganz PA (2009) Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial. Breast Cancer Res Treat 113(2):315–320. doi:10.1007/s10549-008-9937-0

    Article  CAS  PubMed  Google Scholar 

  29. Zhao J, Liu J, Chen K, Li S, Wang Y, Yang Y, Deng H, Jia W, Rao N, Liu Q, Su F (2014) What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis. Breast Cancer Res Treat 145(1):113–128. doi:10.1007/s10549-014-2914-x

    Article  CAS  PubMed  Google Scholar 

  30. Gorodeski GI, Beery R, Lunenfeld B, Geier A (1992) Tamoxifen increases plasma estrogen-binding equivalents and has an estradiol agonistic effect on histologically normal premenopausal and postmenopausal endometrium. Fertil Steril 57(2):320–327

    CAS  PubMed  Google Scholar 

  31. Zaino RJ, Satyaswaroop PG, Mortel R (1985) Hormonal therapy of human endometrial adenocarcinoma in a nude mouse model. Cancer Res 45(2):539–541

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Data were from the Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence––SEER 13 Regs Research Data, Nov 2011 Sub, Vintage 2009 Pops (1992–2009) < Katrina/Rita Population Adjustment>––Linked To County Attributes––Total U.S., 1969–2010 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2012, based on the November 2011 submission.

Conflict of interest

The authors indicated no potential conflicts of interest.

Author information

Author notes

    Authors and Affiliations

    1. Department of Breast Surgery, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

      Jieqiong Liu, Fengxi Su & Qiang Liu

    2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

      Jieqiong Liu & Lisa K. Jacobs

    3. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

      Wen Jiang

    4. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China

      Kai Mao

    5. Department of Radiation Oncology, Yale New Haven Hospital, New Haven, CT, USA

      Yi An

    6. Department of Neurological Surgery, Mayo Clinic Florida, Jacksonville, FL, USA

      Betty Y. S. Kim

    Authors
    1. Jieqiong Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Wen Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Kai Mao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Yi An
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Fengxi Su
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Betty Y. S. Kim
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Qiang Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Lisa K. Jacobs
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Qiang Liu or Lisa K. Jacobs.

    Additional information

    Jieqiong Liu and Wen Jiang contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Liu, J., Jiang, W., Mao, K. et al. Elevated risks of subsequent endometrial cancer development among breast cancer survivors with different hormone receptor status: a SEER analysis. Breast Cancer Res Treat 150, 439–445 (2015). https://doi.org/10.1007/s10549-015-3315-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10549-015-3315-5

    Keywords

    Search

    Navigation