Skip to main content
Top

14-05-2018 | Breast cancer | Article

Effect of glucocorticoid use on survival in patients with stage I–III breast cancer

Journal: Breast Cancer Research and Treatment

Authors: Ching-Hung Lin, Po-Ya Chuang, San-Lin You, Chun-Ju Chiang, Chiun-Sheng Huang, Ming-Yang Wang, Ming Chao, Yen-Shen Lu, Ann-Lii Cheng, Chao-Hsiun Tang

Publisher: Springer US

Abstract

Purpose

Glucocorticoids (GCs) are commonly used in breast cancer patients to ameliorate emesis induced by chemotherapy. Some preclinical studies have suggested that systemic GCs might promote survival of estrogen receptor (ER)-negative breast cancer cells. This study aims to clarify their clinical effect on patient survival.

Methods

A total of 18,596 women with newly diagnosed stage I–III breast cancer in 2002–2006 were identified from the Taiwan Cancer Database and drug treatment was examined from the Taiwan National Health Insurance Claims Database. Of these, 3989 who did not receive adjuvant chemotherapy (non-chemotherapy cohort) and 3237 patients who received six cycles of adjuvant anthracycline-based chemotherapy (anthracycline cohort) were included. The impact of GC use on survival was analyzed separately in these two cohorts using Cox proportional hazards models.

Results

In the non-chemotherapy cohort, GC use was associated with aggressive clinicopathological features of breast cancer. High-dose GC was associated with shorter overall survival in univariate analysis but not in multivariate analysis. In the anthracycline cohort, multivariate analysis showed that GC use at each dose level was significantly associated with longer breast cancer-specific survival (HR 0.65, 0.70, and 0.70 for low-dose, median-dose, and high-dose GC, respectively) and overall survival (HR 0.72, 0.76, and 0.73, respectively) when compared with those receiving no GC. The associations were significant in both ER-positive and ER-negative subgroups for breast cancer-specific survival, and in ER-negative subgroup for overall survival.

Conclusion

Concomitant use of GC improved survival in patients receiving adjuvant anthracycline-based chemotherapy for stage I–III breast cancer.
Literature
1.
Rutz HP (2002) Effects of corticosteroid use on treatment of solid tumours. Lancet 360:1969–1970CrossRefPubMed
2.
Zhang C, Beckermann B, Kallifatidis G et al (2006) Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma. Int J Oncol 29:1295–1301PubMed
3.
Zhao JY, Ikeguchi M, Eckersberg T, Kuo MT (1993) Modulation of multidrug resistance gene expression by dexamethasone in cultured hepatoma cells. Endocrinology 133:521–528CrossRefPubMed
4.
Biswas T, Ramana CV, Srinivasan G et al (1999) Activation of human O6-methylguanine-DNA methyltransferase gene by glucocorticoid hormone. Oncogene 18:525–532CrossRefPubMed
5.
Naumann U, Durka S, Weller M (1998) Dexamethasone-mediated protection from drug cytotoxicity: association with p21WAF1/CIP1 protein accumulation? Oncogene 17:1567–1575CrossRefPubMed
6.
Wu W, Chaudhuri S, Brickley DR et al (2004) Microarray analysis reveals glucocorticoid-regulated survival genes that are associated with inhibition of apoptosis in breast epithelial cells. Cancer Res 64:1757–1764CrossRefPubMed
7.
de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37CrossRefPubMed
8.
Herr I, Marme A (2005) Glucocorticoids and progression of breast cancer. Cancer Biol Ther 4:1415–1416CrossRefPubMed
9.
Schmidt S, Rainer J, Ploner C et al (2004) Glucocorticoid-induced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance. Cell Death Differ 11(Suppl 1):S45–S55CrossRefPubMed
10.
Keith BD (2008) Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy. BMC Cancer 8:84CrossRefPubMedPubMedCentral
11.
Jakobsen A, Frederiksen PL, Moller KA et al (1986) Medroxyprogesterone acetate and prednisone in advanced breast cancer. A randomized trial. Eur J Cancer Clin Oncol 22:1067–1072CrossRefPubMed
12.
Mercer PM, Ebbs SR, Fraser SC et al (1993) Trial of aminoglutethimide vs hydrocortisone as second-line hormone treatment of advanced breast cancer. Eur J Surg Oncol 19:254–258PubMed
13.
Stewart JF, Rubens RD, King RJ et al (1982) Contribution of prednisolone to the primary endocrine treatment of advanced breast cancer. Eur J Cancer Clin Oncol 18:1307–1314CrossRefPubMed
14.
Ingle JN, Mailliard JA, Schaid DJ et al (1991) A double-blind trial of tamoxifen plus prednisolone versus tamoxifen plus placebo in postmenopausal women with metastatic breast cancer. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic. Cancer 68:34–39CrossRefPubMed
15.
Cocconi G, Bisagni G, Ceci G et al (1992) Low-dose aminoglutethimide with and without hydrocortisone replacement as a first-line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research. J Clin Oncol 10:984–989CrossRefPubMed
16.
Rubens RD, Tinson CL, Coleman RE et al (1988) Prednisolone improves the response to primary endocrine treatment for advanced breast cancer. Br J Cancer 58:626–630CrossRefPubMedPubMedCentral
17.
Tormey DC, Gray R, Gilchrist K et al (1990) Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial. Cancer 65:200–206CrossRefPubMed
18.
Marini G, Murray S, Goldhirsch A et al (1996) The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer. International (Ludwig) Breast Cancer Study Group. Ann Oncol 7:245–250CrossRefPubMed
19.
Lippman M, Bolan G, Huff K (1976) The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4602–4609PubMed
20.
Goya L, Maiyar AC, Ge Y, Firestone GL (1993) Glucocorticoids induce a G1/G0 cell cycle arrest of Con8 rat mammary tumor cells that is synchronously reversed by steroid withdrawal or addition of transforming growth factor-alpha. Mol Endocrinol 7:1121–1132PubMed
21.
Hundertmark S, Buhler H, Rudolf M et al (1997) Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells. J Endocrinol 155:171–180CrossRefPubMed
22.
Mikosz CA, Brickley DR, Sharkey MS et al (2001) Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J Biol Chem 276:16649–16654CrossRefPubMed
23.
Wu W, Pew T, Zou M et al (2005) Glucocorticoid receptor-induced MAPK phosphatase-1 (MPK-1) expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival. J Biol Chem 280:4117–4124CrossRefPubMed
24.
Chen Z, Lan X, Wu D et al (2015) Ligand-dependent genomic function of glucocorticoid receptor in triple-negative breast cancer. Nat Commun 6:8323CrossRefPubMedPubMedCentral
25.
Lin CH, Chuang PY, Chiang CJ et al (2014) Distinct clinicopathological features and prognosis of emerging young-female breast cancer in an East Asian country: a nationwide cancer registry-based study. Oncologist 19:583–591CrossRefPubMedPubMedCentral
26.
Wu CY, Chen YJ, Ho HJ et al (2012) Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA 308:1906–1914CrossRefPubMed
27.
Hu C (1999) Steroid equivalence converter. http://​www.​medcalc.​com/​steroid.​html
28.
Pan D, Kocherginsky M, Conzen SD (2011) Activation of the glucocorticoid receptor is associated with poor prognosis in estrogen receptor-negative breast cancer. Cancer Res 71:6360–6370CrossRefPubMedPubMedCentral
29.
DiMartino L, Demontis B, Mitchell IP et al (1991) A randomized clinical trial to investigate the usefulness of the addition of prednisolone to tamoxifen as adjuvants to mastectomy in primary breast cancer patients with a high risk of recurrence: a preliminary report. Anticancer Res 11:869–872PubMed
30.
Fentiman IS, Howell A, Hamed H et al (1994) A controlled trial of adjuvant tamoxifen, with or without prednisolone, in post-menopausal women with operable breast cancer. Br J Cancer 70:729–731CrossRefPubMedPubMedCentral
31.
Lietzen LW, Ahern T, Christiansen P et al (2014) Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study. Ann Oncol 25:2419–2425CrossRefPubMedPubMedCentral
32.
Kawamura A, Tamaki N, Kokunai T (1998) Effect of dexamethasone on cell proliferation of neuroepithelial tumor cell lines. Neurol Med Chir 38:633–638 (Discussion 638–640) CrossRef
33.
Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72CrossRefPubMed
34.
Galluzzi L, Buque A, Kepp O et al (2017) Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol 17:97–111CrossRefPubMed
35.
Casares N, Pequignot MO, Tesniere A et al (2005) Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 202:1691–1701CrossRefPubMedPubMedCentral
36.
Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed
37.
Schiavoni G, Sistigu A, Valentini M et al (2011) Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res 71:768–778CrossRefPubMed
38.
Cook AM, McDonnell AM, Lake RA, Nowak AK (2016) Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies. Oncoimmunology 5:e1066062CrossRefPubMed
39.
Ladoire S, Mignot G, Dabakuyo S et al (2011) In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol 224:389–400CrossRefPubMed