Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer
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The importance of establishing hormone receptor status of tumors for the treatment of women with hormone receptor-positive breast cancer has been emphasized, however, there is no general agreement as to how immunohistochemical assays should be evaluated. It is critical to evaluate hormone recptor status when considering response to endocrine therapy.
Estrogen receptor (ER) and progesterone receptor (PgR) expression was examined by immunohistochemistry using Allred’s score for primary breast tumors from 75 metastatic breast cancer patients who received first-line treatment with endocrine therapy (56 patients received tamoxifen, 11 patients received aromatase inhibitors, and 8 patients received LH-RH agonist or other endocrine reagents) on relapse. Correlation between hormone receptor status and response to endocrine therapy as well as post-relapse survival was analyzed.
The most significant correlation between positive ER expression and response to any endocrine therapy (p=0.011) or tamoxifen only (p=0.030) occurred when the cutoff score was set at 10%. When the evaluation was based on Allred’s score (TS), a cutoff point of TS ≧4 showed a more significant association between positive ER expression and response to all kinds of endocrine therapy (p=0.020) or tamoxifen only (p=0.047). When evaluated at a cutoff point of 1% positive cells, there were fifteen patients with both ER- and PgR-negative tumors, and three patients (20.0%) responded to the therapy. Patients with 1% or more ER or PgR positive cells had better survival after relapse (p=0.0005 andp=0.0008, respectively).
The proportion score alone might be enough to predict hormone responsiveness and post-relapse survival in metastatic breast cancer. The cutoff might be set low, for example 1%, especially for metastatic disease.
- Reiner A, Neumeister B, Spona J, Reiner G, Schemper M, Jakesz R: Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer.Cancer Res 50:7057–7061, 1990.
- Kinsel LB, Szabo E, Greene GL,Konrath aJ, Leight GS, McCarty KS, Jr.: Immunocytochemical analysis of estrogen receptors as a predictor of prognosis in breast cancer patients: comparison with quantitative biochemical methods.Cancer Res 49:1052–1056, 1989.
- Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis.Mod Pathol 11:155–168, 1998.
- Barnes DM, Millis RR, Beex LV, Thorpe SM, Leake RE: Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance.Eur J Cancer 34:1677–1682, 1998. CrossRef
- Harvey JM, Clark GM, Osborne CK, Allred DC: 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 17:1474–1481, 1999.
- Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thurlimann B, Senn HJ: Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer.J Clin Oncol 21:3357–3365, 2003. CrossRef
- Yamashita H, Nishio M, Toyama T, Sugiura H, Zhang Z, Kobayashi S, Iwase H: Coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer.Breast Cancer Res 6:R24–30, 2004. CrossRef
- Rhodes A, Jasani B, Barnes DM, Bobrow LG, Miller KD: Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems.J Clin Pathol 53:125–130, 2000. CrossRef
- Rhodes A, Jasani B, Balaton AJ, Miller KD: Immunohistochemical demonstration of oestrogen and progesterone receptors: correlation of standards achieved on in house tumours with that achieved on external quality assessment material in over 150 laboratories from 26 countries.J Clin Pathol 53:292–301, 2000. CrossRef
- Rhodes A, Jasani B, Balaton AJ, Barnes DM, Miller KD: Frequency of oestrogen and progesterone receptor positivity by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening.J Clin Pathol 53:688–696, 2000. CrossRef
- Leake R, Barnes D, Pinder S, Ellis I, Anderson L, Anderson T, Adamson R, Rhodes T, Miller K, Walker R: Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. UK Receptor Group, UK NEQAS, The Scottish Breast Cancer Pathology Group, and The Receptor and Biomarker Study Group of the EORTC.J Clin Pathol 53:634–635, 2000. CrossRef
- Elledge RM, Osborne CK: Oestrogen receptors and breast cancer.Bmj 314:1843–1844, 1997.
- 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 21:1973–1979, 2003. CrossRef
- Cui X, Zhang P, Deng W, Oesterreich S, Lu Y, Mills GB, Lee AV: Insulin-like growth factor-I inhibits progesterone receptor expression in breast cancer cells via the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway: progesterone receptor as a potential indicator of growth factor activity in breast cancer.Mol Endocrinol 17:575–588, 2003. CrossRef
- Petz LN, Ziegler YS, Schultz JR, Nardulli AM: Fos and Jun inhibit estrogen-induced transcription of the human progesterone receptor gene through an activator protein-1 site.Mol Endocrinol 18:521–532, 2004. CrossRef
- Dowsett M, Harper-Wynne aC, Boeddinghaus I, Salter J, Hills M, Dixon M, Ebbs S, Gui G, Sacks N, Smith I: HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer.Cancer Res 61:8452–8458, 2001.
- Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R: Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer.J Natl Cancer Inst 95:353–361, 2003. CrossRef
- Osborne CK, Shou J, Massarweh S, Schiff R: Cross-talk between estrogen receptor and growth factor receptor pathways as a cause for endocrine therapy resistance in breast cancer.Clin Cancer Res 11:865s-870s, 2005.
- Dowsett M: Overexpression of HER-2 as a resistance mechanism to hormonal therapy for breast cancer.Endocr Relat Cancer 8:191–195, 2001. CrossRef
- Ellis MJ, Coop A, Singh B, Mauriac L, Llombert-Cus-sac A, Janicke F, Miller WR, Evans DB, Dugan M, Brady C, Quebe-Fehling E, Borgs M: Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer: evidence from a phase III randomized trial.J Clin Oncol 19:3808–3816, 2001.
- Arpino G, Green SJ, Allred DC, Lew D, Martino S, Osborne CK, Elledge RM: HER-2 amplification, HER-1 expression, and tamoxifen response in estrogen receptor-positive metastatic breast cancer: a south-west oncology group study.Clin Cancer Res 10:5670–5676, 2004. CrossRef
- Immunohistochemical evaluation of hormone receptor status for predicting response to endocrine therapy in metastatic breast cancer
Volume 13, Issue 1 , pp 74-83
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- Breast cancer
- Estrogen receptor
- Progesterone receptor
- Endocrine therapy
- Industry Sectors
- Author Affiliations
- 1. Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-ku, 467-8601, Nagoya, Japan
- 2. Breast and Endocrine Surgery, Kumamoto University, Japan