Annals of Surgical Oncology

, Volume 20, Issue 5, pp 1505–1513 | Cite as

Lack of Either Estrogen or Progesterone Receptor Expression Is Associated with Poor Survival Outcome among Luminal A Breast Cancer Subtype

  • Seho Park
  • Byeong-Woo ParkEmail author
  • Tae Hyun Kim
  • Chang Wan Jeon
  • Han-Sung Kang
  • Jung-Eun Choi
  • Ki-Tae Hwang
  • In Cheol Kim
Breast Oncology



This study was designed to evaluate the impact of lack of either estrogen receptor (ER) or progesterone receptor (PR) on characteristics and outcomes among luminal A breast cancer subtype treated with endocrine with or without chemotherapeutic agents.


The luminal A subtype was categorized into three subgroups: ER+/PR+, ER+/PR−, and ER−/PR+. All tumors were human epidermal growth factor receptor 2 (HER2) negative. Clinicopathological features and survival were analyzed using the Severance Hospital dataset (n = 1,180) and were validated by the nationwide Korean Breast Cancer Society (KBCS) registry (n = 9,916).


Despite the different distribution of ER/PR status, tumor stage, grade, and local therapies between the two datasets, similarly ER+/PR+ showed smaller size and good differentiation, ER+/PR− patients had the oldest age at diagnosis, and ER−/PR+ was associated with the youngest age at onset and grade III tumor. Single hormone receptor-positive subgroups demonstrated worse disease-related outcomes than the ER+/PR+ subgroup. These associations were confirmed by the KBCS dataset. This trend was also demonstrated in the subpopulation of 1,944 patients with Ki-67 < 14 %. Inferior survival of single receptor-positive tumors was more definite among node-positive patients even when receiving both chemo-endocrine therapies.


Current results suggest that the luminal A subtype is also heterogeneous and each subgroup has unique clinicopathologic characteristics. Lack of either ER or PR expression is associated with worse survival, especially among node-positive luminal A subtype.


Overall Survival Estrogen Receptor Luminal Progesterone Receptor Progesterone Receptor Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



A major part of this study was presented at the Global Breast Cancer Conference 2011, in Seoul, Korea during the poster discussion on October 6–8, 2011. The Korean Breast Cancer Society especially thanks its members who participated in the National Registration Program and all Korean women with breast cancer.

Conflict of interest

The authors declare that they have no conflicts of interest to disclose.

Supplementary material

10434_2012_2772_MOESM1_ESM.doc (90 kb)
Supplementary material 1 (DOC 89 kb)


  1. 1.
    Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.PubMedCrossRefGoogle Scholar
  2. 2.
    Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Nielsen TO, Hsu FD, Jensen K, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.PubMedCrossRefGoogle Scholar
  5. 5.
    Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295:2492–502.PubMedCrossRefGoogle Scholar
  6. 6.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.PubMedCrossRefGoogle Scholar
  7. 7.
    Cheang MC, Chia SK, Voduc D, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.PubMedCrossRefGoogle Scholar
  8. 8.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.Google Scholar
  9. 9.
    Rakha EA, El-Sayed ME, Green AR, et al. Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol. 2007;25:4772–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Cui X, Schiff R, Arpino G, Osborne CK, Lee AV. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005;23:7721–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771–84.Google Scholar
  12. 12.
    Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003;21:1973–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu S, Chia SK, Mehl E, Leung S, Rajput A, Cheang MC, Nielsen TO. Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients. Breast Cancer Res Treat. 2010;119:53–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Nadji M, Gomez-Fernandez C, Ganjei-Azar P, Morales AR. Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. Am J Clin Pathol. 2005;123:21–7.PubMedCrossRefGoogle Scholar
  15. 15.
    De Maeyer L, Van Limbergen E, De Nys K, et al. Does estrogen receptor negative/progesterone receptor positive breast carcinoma exist? J Clin Oncol. 2008;26:335–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Kiani J, Khan A, Khawar H, Shuaib F, Pervez S. Estrogen receptor alpha-negative and progesterone receptor-positive breast cancer: lab error or real entity? Pathol Oncol Res. 2006;12:223–7.PubMedCrossRefGoogle Scholar
  17. 17.
    von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7.CrossRefGoogle Scholar
  18. 18.
    Greene FL, American Joint Committee on Cancer, American Cancer Society. AJCC cancer staging manual, 6th ed. New York: Springer; 2002.Google Scholar
  19. 19.
    Hammond ME, Hayes DF, Wolff AC, Mangu PB, Temin S. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract. 2010;6:195–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko SS, Han W. Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea-a report from the Korean Breast Cancer Society. J Clin Oncol. 2007;25:2360–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Thakkar JP, Mehta DG. A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative. Oncologist. 2011;16:276–85.PubMedCrossRefGoogle Scholar
  23. 23.
    Dunnwald LK, Rossing MA, Li CI. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007;9:R6.PubMedCrossRefGoogle Scholar
  24. 24.
    Creighton CJ, Kent Osborne C, van de Vijver MJ, et al. Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat. 2009;114:287–99.PubMedCrossRefGoogle Scholar
  25. 25.
    Rhodes A, Jasani B. The oestrogen receptor-negative/progesterone receptor-positive breast tumour: a biological entity or a technical artefact? J Clin Pathol. 2009;62:95–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Yu KD, Di GH, Wu J, et al. Breast cancer patients with estrogen receptor-negative/progesterone receptor-positive tumors: being younger and getting less benefit from adjuvant tamoxifen treatment. J Cancer Res Clin Oncol. 2008;134:1347–54.PubMedCrossRefGoogle Scholar
  27. 27.
    Horwitz KB. Cellular heterogeneity and mutant oestrogen receptors in hormone resistant breast cancer. Cancer Surv. 1992;14:41–54.PubMedGoogle Scholar
  28. 28.
    Cserni G, Francz M, Kalman E, et al. Estrogen receptor negative and progesterone receptor positive breast carcinomas-how frequent are they? Pathol Oncol Res. 2011;17:663–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Viale G, Regan MM, Maiorano E, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol. 2007;25:3846–52.PubMedCrossRefGoogle Scholar
  30. 30.
    Dowsett M, Allred C, Knox J, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26:1059–65.PubMedCrossRefGoogle Scholar
  31. 31.
    Bartlett JM, Brookes CL, Robson T, et al. Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial. J Clin Oncol. 2011;29:1531–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006;7:347–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Bogaerts J, Cardoso F, Buyse M, et al. Gene signature evaluation as a prognostic tool: challenges in the design of the MINDACT trial. Natl Clin Pract Oncol. 2006;3:540–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Carlson RW, Allred DC, Anderson BO, et al. Breast cancer. Clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2009;7:122–92.PubMedGoogle Scholar
  35. 35.
    Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.PubMedCrossRefGoogle Scholar
  36. 36.
    Cuzick J, Dowsett M, Pineda S, et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol. 2011;29:4273–8.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Seho Park
    • 1
  • Byeong-Woo Park
    • 1
    • 2
    Email author
  • Tae Hyun Kim
    • 3
  • Chang Wan Jeon
    • 4
  • Han-Sung Kang
    • 5
  • Jung-Eun Choi
    • 6
  • Ki-Tae Hwang
    • 7
  • In Cheol Kim
    • 8
  1. 1.Department of SurgeryYonsei University College of Medicine, Seoul and Target Molecule Study Group, The Korean Breast Cancer SocietySeoulRepublic of Korea
  2. 2.Brain Korea 21 Project for Medical ScienceYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Department of SurgeryBusan Paik Hospital, Inje University College of Medicine, Busan and Target Molecule Study Group, The Korean Breast Cancer SocietySeoulRepublic of Korea
  4. 4.Department of SurgeryCancer Center, Dongnam Institute of Radiological & Medical Sciences, Busan and Target Molecule Study Group, The Korean Breast Cancer SocietySeoulRepublic of Korea
  5. 5.Center for Breast CancerNational Cancer CenterGoyangRepublic of Korea
  6. 6.Department of SurgeryYeungnam University College of MedicineDaeguRepublic of Korea
  7. 7.Department of SurgerySeoul National University Boramae Medical CenterSeoulRepublic of Korea
  8. 8.Department of SurgeryBreast Cancer Center, Saegyaero HospitalBusanRepublic of Korea

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