Breast Cancer Research and Treatment

, Volume 90, Issue 1, pp 65–70

Impact of metastatic estrogen receptor and progesterone receptor status on survival

  • Elyse E. Lower
  • Eleanor L. Glass
  • Deborah A. Bradley
  • Robbin Blau
  • Sue Heffelfinger
Report

Summary

Hormone responsive breast cancer is usually determined by the presence of estrogen receptors (ER) or progesterone receptors (PR) on primary invasive breast cancers. Adjuvant and metastatic hormone therapy are recommended based on primary ER and PR determination. Little information is available to determine if primary hormone receptors correlate with metastatic disease and if survival is influenced by metastatic receptor status. We retrospectively compared primary to metastatic tumor ER and PR content from 200 metastatic breast cancer patients. ER and PR analyses were available in both primary and metastatic disease in 200 and 173 patients, respectively. There was a correlation between both the ER and PR in the primary and metastatic lesion (p < 0.001). However, in 60 of 200 (30%) patients, discordance between primary and metastatic ER was noted. Tumors from 68 of 173 (39.3%) showed discordance for PR. In 39 (19.5%) patients, the ER primary status was positive and metastatic status was negative and in 21 (10.5%) patients, the primary status was negative and metastatic status was positive. Survival from the time of metastatic diagnosis was calculated. Those patients with ER positive primary and metastatic tumors (Positive/Positive) or only the metastatic lesion (Negative/Positive) had similar median survival (1131 and 1111 days, respectively). However, patients with tumors that changed from positive primary to negative metastasis (Positive/Negative) experienced significantly shorter median survival (669 days, p < 0.05). Likewise, median survival (580 days) was significantly shorter for patients with primary and metastasis ER negative (Negative/Negative, p < 0.001) compared to Positive/Positive (p < 0.001) or compared to Negative/Positive (p < 0.02). The changes in PR status were not associated with a change in survival. We found a significant discordance between hormone receptor content of primary versus metastatic breast cancer. The ER status of the metastatic lesion was a better predictor of survival. Therefore, optimal metastatic treatment cannot be determined solely on primary ER and PR analysis.

Keywords

Breast cancer estrogen receptors hormone therapy metastatic hormone receptors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Buzdar, AU, Hortobagyi, G 1998Update on endocrine therapy for breastcancerClin Cancer Res4527534Google Scholar
  2. Osborne, CK, Yochmowitz, MG, Knight, WA,III, McGuire, WL 1980The value of estrogen and progesterone receptors in the treatment of breast cancerCancer4628842888Google Scholar
  3. Early Breast Cancer Trialists Collaborative Group1998Tamoxifen for early breast cancer:an overview of the randomized trials.Early Breast Cancer Collaborative Group.Lancet35114511467Google Scholar
  4. Elledge, RM, Fuqua, SAW 2000

    Estrogen and progesterone receptors

    Harris, JRLippman, MEMorrow, MOsborne, CK eds. Diseases of the BreastLippincott Williams & WilkensPhiladelphia471488
    Google Scholar
  5. Mouridsen, H, Gershanovich, M, Sun, Y,  et al. 2003Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer GroupJ Clin Oncol2121012109Google Scholar
  6. Nabholtz, JM, Bonneterre, J, Buzdar, A, Robertson, JF, Thurliman, B 2003Anastrozole (Arimidex) versus tamoxifen as first line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety resultsEur J Cancer3916841689CrossRefPubMedGoogle Scholar
  7. DelaHaba-Rodriguez, JR, Ruiz, BM, Gomez, EA,  et al. 2004Comparative study of the immunohistochemical phenotype in breast cancer and its lymph node metastatic locationCancer Invest22219224Google Scholar
  8. Hortobagyi, GN 2003Future directions in the endocrine therapy of breast cancerBreast Cancer Res Treat 801S37S39 (Suppl)Google Scholar
  9. Lower, EE, Franco, RS, Miller, MA, Martelo, OJ 1993Enzymatic and immunohistochemical evaluation of tyrosine phosphorylation in breast cancer specimensBreast Cancer Res Treat26217224Google Scholar
  10. Allred, DC, Harvey, JM, Berardo, M, Clark, GM 1998Prognostic and predictive factors in breast cancer by immunohistochemical analysisMod Pathol11155168Google Scholar
  11. Lower, EE, Blau, R, Gazder, P, Stahl, DL 1999The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancerBreast Cancer Res Treat58205211Google Scholar
  12. Hollander, MWolfe, DA eds. 1999Nonparametric Statistical Methods2WileyNew YorkGoogle Scholar
  13. Blamey, RW 2002Guidelines on endocrine therapy of breast cancer EUSOMAEur J Cancer38615634Google Scholar
  14. Campbell, FC, Blamey, RW, Elston, CW,  et al. 1981Quantitative oestradiol receptor values in primary breast cancer and response of metastases to endocrine therapyLancet213171319Google Scholar
  15. Raemaekers, JM, Beex, LV, Pieters, GF,  et al. 1987 Progesterone receptor activity and the response to the first endocrine therapy in advanced breast cancerEur J Cancer Clin Oncol23443448Google Scholar
  16. Osborne, CK 1985Heterogeneity in hormone receptor status in primary and metastatic breast cancerSemin Oncol12317326Google Scholar
  17. Tilley, WD, Keightley, DD, Cant, EL 1978Inter-site variation of oestrogen receptors in human breast cancersBr J Cancer38544546Google Scholar
  18. Davis, BW, Zava, DT, Locher, GW, Goldhirsch, A, Hartmann, WH 1984Receptor heterogeneity of human breast cancer as measured by multiple intratumoral assays of estrogen and progesterone receptorEur J Cancer Clin Oncol20375382Google Scholar
  19. Kiang, DT, Kennedy, BJ 1977Factors affecting estrogen receptors in breast cancerCancer4015711576Google Scholar
  20. Gross, GE, Clark, GM, Chamness, GC, McGuire, WL 1984Multiple progesterone receptor assays in human breast cancerCancer Res44836840Google Scholar
  21. Hull, DF,III, Clark, GM, Osborne, CK,  et al. 1983Multiple estrogen receptor assays in human breast cancerCancer Res43413416Google Scholar
  22. Hawkins, RA, Black, R, Steele, RJC, Dixon, JMJ, McEwan Forest, AP 1981Oestrogen receptor concentration in primary breast cancer and axillary node metastasesBreast Cancer Res Treat1245251Google Scholar
  23. Hahnel, R, Twaddle, E 1985The relationship between estrogen receptors in primary and secondary breast carcinomas and in sequential primary breast carcinomasBreast Cancer Res Treat5155163Google Scholar
  24. Li, BD, Byskosh, A, Molteni, A, Duda, RB 1994Estrogen and progesterone receptor concordance between primary and recurrent breast cancerJ Surg Oncol577177Google Scholar
  25. Mori, T, Morimoto, T, Komaki, K, Monden, Y 1991Comparison of estrogen receptor and epidermal growth factor receptor content of primary and involved nodes in human breast cancerCancer68532537Google Scholar
  26. Kuukasjarvi, T, Kononen, J, Helin, H, Holli, K, Isola, J 1996Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapyJ Clin Oncol1425842589Google Scholar
  27. Kamby, C, Rasmussen, BB, Kristensen, B 1989Oestrogen receptor status of primary breast carcinomas and their metastases relation to pattern of spread and survival after recurrence.Br J Cancer60252257Google Scholar
  28. Mouridsen, H, Gershanovich, M 2003The role of aromatase inhibitors in the treatment of metastatic breast cancerSemin Oncol303345Google Scholar
  29. Bross, PF, Baird, A, Chen, G,  et al. 2003Fulvestrant in postmenopausal women with advanced breast cancerClin Cancer Res943094317Google Scholar
  30. Sekido, Y, Umemura, S, Takekoshi, S,  et al. 2003Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutationInt J Oncol2212251232Google Scholar
  31. Zheng, WQ, Lu, J, Zheng, JM, Hu, FX, Ni, CR 2001Variation of ER status between primary and metastatic breast cancer and relationship to p53 expressionSteroids66905910Google Scholar
  32. Hopp, TA, Fuqua, SA 1998Estrogen receptor variantsJ Mammary Gland Biol Neoplasia37383Google Scholar
  33. Umekita, Y, Sagara, Y, Yoshida, H 1998Estrogen receptor mutations and changes in estrogen receptor and progesterone receptor protein expression in metastatic or recurrent breast cancerJpn J Cancer Res892732Google Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Elyse E. Lower
    • 1
    • 2
    • 3
  • Eleanor L. Glass
    • 1
  • Deborah A. Bradley
    • 1
  • Robbin Blau
    • 2
  • Sue Heffelfinger
    • 2
  1. 1.Department of Internal MedicineUniversity of Cincinnati College of MedicineCincinnati
  2. 2.Oncology–Hematology CareCincinnatiUSA
  3. 3.University of Cincinnati Medical CenterCincinnatiUSA

Personalised recommendations