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Characterization of estrogen receptor-low-positive breast cancer

  • Epidemiology
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Abstract

Purpose

The biology of breast cancer with a low expression level (1–10%) of estrogen receptor (ER) remains a matter of confusion. The recent American Society of Oncology/College of American Pathologist Guidelines have recommended reporting such tumors as a new “ER-low-positive” category with a recommended comment to emphasize the possible overall benefit of endocrine therapies in these patients. The aim of the study was to analyze the clinicopathologic features and clinical outcomes of ER-low-positive breast cancers.

Methods

We characterized the clinicopathologic features and survival outcomes of ER-low-positive breast cancers in our 4179 patients diagnosed from 1998 to 2018.

Results

The ER-positive, ER-low-positive, and ER-negative cases in our cohort were 2982 (71.4%), 97 (2.3%), and 1100 (26.3%), respectively. ER-low-positive tumors showed similar clinicopathologic characteristics yet significantly superior prognosis when compared to ER-negative tumors, while demonstrated largely overlapping survival outcomes with ER-positive tumors in the entire cohort. In the subcohort of tumors with a PR-positive phenotype, the prognosis of ER-low-positive tumors was intermediate between that of the ER-positive and ER-negative groups. ER-low-positive/PR-positive tumors had a significantly worse prognosis than ER-positive tumors, and a trend toward favorable survival outcomes when compared to ER-negative tumors, although no significant difference was identified for the latter. In contrast, the ER-positive and ER-low-positive groups showed similar survival outcomes in the subset of tumors with a PR-negative status, both being significantly better than ER-negative tumors.

Conclusions

PR status as a surrogate marker of functional ER signaling provides critical information in this regard. These findings suggest that while ER-low-positive tumors are themselves heterogeneous, they often respond to endocrine treatment. Analysis of molecular signatures and standardization of therapeutic strategies are important to understand the biology of ER-low-positive tumors and to enable optimal treatment in the pursuit of individualized medicine.

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References

  1. Bartlett JM, Brookes CL, Robson T, van de Velde CJ, Billingham LJ, Campbell FM, Grant M, Hasenburg A, Hille ET, Kay C et al (2011) 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 29(12):1531–1538

    Article  CAS  Google Scholar 

  2. Cianfrocca M, Goldstein LJ (2004) Prognostic and predictive factors in early-stage breast cancer. Oncologist 9(6):606–616

    Article  Google Scholar 

  3. Harvey JM, Clark GM, Osborne CK, Allred DC (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 17(5):1474–1481

    Article  CAS  Google Scholar 

  4. Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O’Malley F, Simpson JF, Connolly JL et al (2000) Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med 124(7):966–978

    Article  CAS  Google Scholar 

  5. Anderson WF, Katki HA, Rosenberg PS (2011) Incidence of breast cancer in the United States: current and future trends. J Natl Cancer Inst 103(18):1397–1402

    Article  Google Scholar 

  6. Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Rowden D, Solky AJ et al (2014) Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: american society of clinical oncology clinical practice guideline focused update. J Clin Oncol 32(21):2255–2269

    Article  Google Scholar 

  7. Bouchard-Fortier A, Provencher L, Blanchette C, Diorio C (2017) Prognostic and predictive value of low estrogen receptor expression in breast cancer. Curr Oncol 24(2):e106–e114

    Article  CAS  Google Scholar 

  8. Early Breast Cancer Trialists’ Collaborative Group, Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C et al (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

    Article  Google Scholar 

  9. Aldrees R, Gao X, Zhang K, Siegal GP, Wei S (2020) Validation of the revised 8th AJCC breast cancer clinical prognostic staging system: analysis of 5321 cases from a single institution. Mod Pathol 34:291–299

    Article  Google Scholar 

  10. Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M et al (2010) American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28(16):2784–2795

    Article  Google Scholar 

  11. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J et al (2020) Estrogen and Progesterone Receptor Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Guideline Update. Arch Pathol Lab Med 144(5):545–563

    Article  CAS  Google Scholar 

  12. Yi M, Huo L, Koenig KB, Mittendorf EA, Meric-Bernstam F, Kuerer HM, Bedrosian I, Buzdar AU, Symmans WF, Crow JR et al (2014) Which threshold for ER positivity? A retrospective study based on 9639 patients. Ann Oncol 25(5):1004–1011

    Article  CAS  Google Scholar 

  13. Chen T, Zhang N, Moran MS, Su P, Haffty BG, Yang Q (2018) Borderline ER-positive primary breast cancer gains no significant survival benefit from endocrine therapy: a systematic review and meta-analysis. Clin Breast Cancer 18(1):1–8

    Article  Google Scholar 

  14. Poon IK, Tsang JY, Li J, Chan SK, Shea KH, Tse GM (2020) The significance of highlighting the oestrogen receptor low category in breast cancer. Br J Cancer 123:1223–1227

    Article  CAS  Google Scholar 

  15. Iwamoto T, Booser D, Valero V, Murray JL, Koenig K, Esteva FJ, Ueno NT, Zhang J, Shi W, Qi Y et al (2012) Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol 30(7):729–734

    Article  Google Scholar 

  16. Prabhu JS, Korlimarla A, Desai K, Alexander A, Raghavan R, Anupama C, Dendukuri N, Manjunath S, Correa M, Raman N et al (2014) A majority of low (1–10%) ER positive breast cancers behave like hormone receptor negative tumors. J Cancer 5(2):156–165

    Article  Google Scholar 

  17. Landmann A, Farrugia DJ, Zhu L, Diego EJ, Johnson RR, Soran A, Dabbs DJ, Clark BZ, Puhalla SL, Jankowitz RC et al (2018) Low estrogen receptor (ER)-positive breast cancer and neoadjuvant systemic chemotherapy: is response similar to typical ER-positive or ER-negative disease? Am J Clin Pathol 150(1):34–42

    Article  CAS  Google Scholar 

  18. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A et al (2007) 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 25(1):118–145

    Article  CAS  Google Scholar 

  19. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31(31):3997–4013

    Article  Google Scholar 

  20. Layfield LJ, Gupta D, Mooney EE (2000) Assessment of tissue estrogen and progesterone receptor levels: a survey of current practice, techniques, and quantitation methods. Breast J 6(3):189–196

    Article  CAS  Google Scholar 

  21. Fujii T, Kogawa T, Dong W, Sahin AA, Moulder S, Litton JK, Tripathy D, Iwamoto T, Hunt KK, Pusztai L et al (2017) Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Ann Oncol 28(10):2420–2428

    Article  CAS  Google Scholar 

  22. Viale G, Regan MM, Maiorano E, Mastropasqua MG, Dell’Orto P, Rasmussen BB, Raffoul J, Neven P, Orosz Z, Braye S et al (2007) 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 25(25):3846–3852

    Article  Google Scholar 

  23. Raghav KP, Hernandez-Aya LF, Lei X, Chavez-Macgregor M, Meric-Bernstam F, Buchholz TA, Sahin A, Do KA, Hortobagyi GN, Gonzalez-Angulo AM (2012) Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers. Cancer 118(6):1498–1506

    Article  CAS  Google Scholar 

  24. Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM (2003) 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 21(10):1973–1979

    Article  CAS  Google Scholar 

  25. Dunnwald LK, Rossing MA, Li CI (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 9(1):R6

    Article  Google Scholar 

  26. Shen T, Brandwein-Gensler M, Hameed O, Siegal GP, Wei S (2015) Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer. Hum Pathol 46(11):1776–1784

    Article  CAS  Google Scholar 

  27. Hortobagyi GN, Connolly JL, D’Orsi CJ, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ, Giuliano AE (2017) Breast. In: Amin MA (ed) AJCC cancer staging manual, 8th edn. New York, Springer, pp 587–628

    Google Scholar 

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Correspondence to Shi Wei.

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Fei, F., Siegal, G.P. & Wei, S. Characterization of estrogen receptor-low-positive breast cancer. Breast Cancer Res Treat 188, 225–235 (2021). https://doi.org/10.1007/s10549-021-06148-0

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  • DOI: https://doi.org/10.1007/s10549-021-06148-0

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