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Erschienen in: Cancer Chemotherapy and Pharmacology 1/2017

24.05.2017 | Original Article

Allred score is a promising predictor of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2017

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Abstract

Purpose

Predictors of response or disease control with oral medroxyprogesterone acetate (MPA) therapy in patients with metastatic or recurrence endometrial cancer remain to be elucidated. The purpose of this study was to clarify the effect of MPA in patients with endometrial cancer and identify markers that predict MPA efficacy.

Methods

We retrospectively analyzed clinical and pathological factors in patients who received MPA. Expression of estrogen receptor, progesterone receptor (PgR), androgen receptor, and Ki67 index was assessed with residual tissue samples of endometrial cancer. Expression levels were evaluated semi-quantitatively using the Allred score. Correlations between expression levels and patients’ characteristics, response to MPA, and survival were assessed.

Results

We analyzed clinical factors in 40 patients and molecular pathological factors in 27 patients for MPA efficacy. The overall response rate was 35% in all 40 patients and there were 10 patients (25%) with continued complete or partial response for over 5 years. However, higher Allred score for PgR (p = 0.050) tended to be and lower Ki67 labeling index (p = 0.001) were significantly predictive factors for long-term complete or partial response over 5 years. Median progression-free survival was 6.4 (2–217) months and the 5-year progression-free survival rate was 32%. Multivariate analysis showed that Allred score ≥3 for PgR (p = 0.039) was the only significant predictive marker for long-term disease control. There were no severe adverse events that resulted in discontinuation of MPA.

Conclusions

This study suggests the utility of MPA when the Allred score for PgR is ≥3. Future prospective studies are needed to confirm these findings.
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Literatur
1.
Zurück zum Zitat Matsuda A, Matsuda T, Shibata A et al (2014) Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 44:388–396CrossRefPubMed Matsuda A, Matsuda T, Shibata A et al (2014) Cancer incidence and incidence rates in Japan in 2008: a study of 25 population-based cancer registries for the Monitoring of Cancer Incidence in Japan (MCIJ) project. Jpn J Clin Oncol 44:388–396CrossRefPubMed
2.
Zurück zum Zitat Aoki D (2014) Annual report of Gynecologic Oncology Committee, Japan Society of Obstetrics and Gynecology, 2013. J Obstet Gynaecol Res 40:338–348CrossRefPubMed Aoki D (2014) Annual report of Gynecologic Oncology Committee, Japan Society of Obstetrics and Gynecology, 2013. J Obstet Gynaecol Res 40:338–348CrossRefPubMed
3.
Zurück zum Zitat Baak JP, Snijders W, van Diermen B, van Diest PJ, Diepenhorst FW, Benraadt J (2003) Prospective multicenter validation confirms the prognostic superiority of the endometrial carcinoma prognostic index in international Federation of gynecology and obstetrics stage 1 and 2 endometrial carcinoma. J Clin Oncol 21:4214–4221CrossRefPubMed Baak JP, Snijders W, van Diermen B, van Diest PJ, Diepenhorst FW, Benraadt J (2003) Prospective multicenter validation confirms the prognostic superiority of the endometrial carcinoma prognostic index in international Federation of gynecology and obstetrics stage 1 and 2 endometrial carcinoma. J Clin Oncol 21:4214–4221CrossRefPubMed
4.
Zurück zum Zitat Vance S, Yechieli R, Cogan C, Hanna R, Munkarah A, Elshaikh MA (2012) The prognostic significance of age in surgically staged patients with Type II endometrial carcinoma. Gynecol Oncol 126:16–19CrossRefPubMed Vance S, Yechieli R, Cogan C, Hanna R, Munkarah A, Elshaikh MA (2012) The prognostic significance of age in surgically staged patients with Type II endometrial carcinoma. Gynecol Oncol 126:16–19CrossRefPubMed
5.
Zurück zum Zitat Chung HH, Lee I, Kim HS et al (2013) Prognostic value of preoperative metabolic tumor volume measured by (1)(8)F-FDG PET/CT and MRI in patients with endometrial cancer. Gynecol Oncol 130:446–451CrossRefPubMed Chung HH, Lee I, Kim HS et al (2013) Prognostic value of preoperative metabolic tumor volume measured by (1)(8)F-FDG PET/CT and MRI in patients with endometrial cancer. Gynecol Oncol 130:446–451CrossRefPubMed
6.
Zurück zum Zitat Dai D, Wolf DM, Litman ES, White MJ, Leslie KK (2002) Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res 62:881–886PubMed Dai D, Wolf DM, Litman ES, White MJ, Leslie KK (2002) Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res 62:881–886PubMed
7.
Zurück zum Zitat Dai D, Litman ES, Schonteich E, Leslie KK (2003) Progesterone regulation of activating protein-1 transcriptional activity: a possible mechanism of progesterone inhibition of endometrial cancer cell growth. J Steroid Biochem Mol Biol 87:123–131CrossRefPubMed Dai D, Litman ES, Schonteich E, Leslie KK (2003) Progesterone regulation of activating protein-1 transcriptional activity: a possible mechanism of progesterone inhibition of endometrial cancer cell growth. J Steroid Biochem Mol Biol 87:123–131CrossRefPubMed
8.
Zurück zum Zitat Davies S, Dai D, Feldman I, Pickett G, Leslie KK (2004) Identification of a novel mechanism of NF-kappaB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2. Gynecol Oncol 94:463–470CrossRefPubMed Davies S, Dai D, Feldman I, Pickett G, Leslie KK (2004) Identification of a novel mechanism of NF-kappaB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2. Gynecol Oncol 94:463–470CrossRefPubMed
9.
Zurück zum Zitat Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT (1996) High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 14:357–361CrossRefPubMed Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT (1996) High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 14:357–361CrossRefPubMed
10.
Zurück zum Zitat Colombo N, Preti E, Landoni F et al (2013) Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6):vi33–vi38CrossRefPubMed Colombo N, Preti E, Landoni F et al (2013) Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24(Suppl 6):vi33–vi38CrossRefPubMed
11.
Zurück zum Zitat National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Uterine Neoplasms, version 2.2016, NCCN.org National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Uterine Neoplasms, version 2.2016, NCCN.org
12.
Zurück zum Zitat Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed
13.
Zurück zum Zitat 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 17:1474–1481CrossRefPubMed 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 17:1474–1481CrossRefPubMed
14.
Zurück zum Zitat Mohsin SK, Weiss H, Havighurst T et al (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17:1545–1554CrossRefPubMed Mohsin SK, Weiss H, Havighurst T et al (2004) Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: a validation study. Mod Pathol 17:1545–1554CrossRefPubMed
15.
Zurück zum Zitat Phillips T, Murray G, Wakamiya K et al (2007) Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol 15:325–331CrossRefPubMed Phillips T, Murray G, Wakamiya K et al (2007) Development of standard estrogen and progesterone receptor immunohistochemical assays for selection of patients for antihormonal therapy. Appl Immunohistochem Mol Morphol 15:325–331CrossRefPubMed
17.
Zurück zum Zitat Japanese translation of common terminology criteria for adverse events (CTCAE), and instructions and guidelines (2004) International J Clin Oncol 9(Suppl 3):1–82 Japanese translation of common terminology criteria for adverse events (CTCAE), and instructions and guidelines (2004) International J Clin Oncol 9(Suppl 3):1–82
18.
Zurück zum Zitat Mortel R, Zaino RJ, Satyaswaroop PG (1990) Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model. Am J Obstet Gynecol 162:928–934CrossRefPubMed Mortel R, Zaino RJ, Satyaswaroop PG (1990) Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model. Am J Obstet Gynecol 162:928–934CrossRefPubMed
19.
Zurück zum Zitat Satyaswaroop PG, Clarke CL, Zaino RJ, Mortel R (1992) Apparent resistance in human endometrial carcinoma during combination treatment with tamoxifen and progestin may result from desensitization following downregulation of tumor progesterone receptor. Cancer Lett 62:107–114CrossRefPubMed Satyaswaroop PG, Clarke CL, Zaino RJ, Mortel R (1992) Apparent resistance in human endometrial carcinoma during combination treatment with tamoxifen and progestin may result from desensitization following downregulation of tumor progesterone receptor. Cancer Lett 62:107–114CrossRefPubMed
20.
Zurück zum Zitat Thigpen JT, Brady MF, Alvarez RD et al (1999) Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 17:1736–1744CrossRefPubMed Thigpen JT, Brady MF, Alvarez RD et al (1999) Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 17:1736–1744CrossRefPubMed
21.
Zurück zum Zitat Knight WA, Livingston RB, Gregory EJ, McGuire WL (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37:4669–4671PubMed Knight WA, Livingston RB, Gregory EJ, McGuire WL (1977) Estrogen receptor as an independent prognostic factor for early recurrence in breast cancer. Cancer Res 37:4669–4671PubMed
22.
Zurück zum Zitat Clark GM, Osborne CK, McGuire WL (1984) Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 2:1102–1109CrossRefPubMed Clark GM, Osborne CK, McGuire WL (1984) Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol 2:1102–1109CrossRefPubMed
23.
Zurück zum Zitat Beck T, Weikel W, Brumm C, Wilkens C, Pollow K, Knapstein PG (1994) Immunohistochemical detection of hormone receptors in breast carcinomas (ER-ICA, PgR-ICA): prognostic usefulness and comparison with the biochemical radioactive-ligand-binding assay (DCC). Gynecol Oncol 53:220–227CrossRefPubMed Beck T, Weikel W, Brumm C, Wilkens C, Pollow K, Knapstein PG (1994) Immunohistochemical detection of hormone receptors in breast carcinomas (ER-ICA, PgR-ICA): prognostic usefulness and comparison with the biochemical radioactive-ligand-binding assay (DCC). Gynecol Oncol 53:220–227CrossRefPubMed
24.
Zurück zum Zitat Zafrani B, Aubriot MH, Mouret E et al (2000) High sensitivity and specificity of immunohistochemistry for the detection of hormone receptors in breast carcinoma: comparison with biochemical determination in a prospective study of 793 cases. Histopathology 37:536–545CrossRefPubMed Zafrani B, Aubriot MH, Mouret E et al (2000) High sensitivity and specificity of immunohistochemistry for the detection of hormone receptors in breast carcinoma: comparison with biochemical determination in a prospective study of 793 cases. Histopathology 37:536–545CrossRefPubMed
25.
Zurück zum Zitat Regan MM, Viale G, Mastropasqua MG et al (2006) Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 98:1571–1581CrossRefPubMed Regan MM, Viale G, Mastropasqua MG et al (2006) Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 98:1571–1581CrossRefPubMed
26.
Zurück zum Zitat Dowsett M, Allred C, Knox J et al (2008) 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 26:1059–1065CrossRefPubMed Dowsett M, Allred C, Knox J et al (2008) 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 26:1059–1065CrossRefPubMed
27.
Zurück zum Zitat Thomson CS, Twelves CJ, Mallon EA, Leake RE, Scottish Cancer Trials Breast G, Scottish Cancer Therapy N (2002) Adjuvant ovarian ablation vs CMF chemotherapy in premenopausal breast cancer patients: trial update and impact of immunohistochemical assessment of ER status. Breast 11:419–429CrossRefPubMed Thomson CS, Twelves CJ, Mallon EA, Leake RE, Scottish Cancer Trials Breast G, Scottish Cancer Therapy N (2002) Adjuvant ovarian ablation vs CMF chemotherapy in premenopausal breast cancer patients: trial update and impact of immunohistochemical assessment of ER status. Breast 11:419–429CrossRefPubMed
28.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett 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 28:2784–2795CrossRefPubMedPubMedCentral Hammond ME, Hayes DF, Dowsett 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 28:2784–2795CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Whitney CW, Brunetto VL, Zaino RJ et al (2004) Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92:4–9CrossRefPubMed Whitney CW, Brunetto VL, Zaino RJ et al (2004) Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92:4–9CrossRefPubMed
30.
Zurück zum Zitat Singh M, Zaino RJ, Filiaci VJ, Leslie KK (2007) Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 106:325–333CrossRefPubMed Singh M, Zaino RJ, Filiaci VJ, Leslie KK (2007) Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: a Gynecologic Oncology Group Study. Gynecol Oncol 106:325–333CrossRefPubMed
31.
Zurück zum Zitat Ehrlich CE, Young PC, Stehman FB, Sutton GP, Alford WM (1988) Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium. Am J Obstet Gynecol 158:796–807CrossRefPubMed Ehrlich CE, Young PC, Stehman FB, Sutton GP, Alford WM (1988) Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium. Am J Obstet Gynecol 158:796–807CrossRefPubMed
32.
Zurück zum Zitat Jongen V, Briet J, de Jong R et al (2009) Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 112:537–542CrossRefPubMed Jongen V, Briet J, de Jong R et al (2009) Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 112:537–542CrossRefPubMed
33.
Zurück zum Zitat Kobel M, Atenafu EG, Rambau PF et al (2016) Progesterone receptor expression is associated with longer overall survival within high-grade histotypes of endometrial carcinoma: a Canadian high risk endometrial cancer consortium (CHREC) study. Gynecol Oncol 141:559–563CrossRefPubMed Kobel M, Atenafu EG, Rambau PF et al (2016) Progesterone receptor expression is associated with longer overall survival within high-grade histotypes of endometrial carcinoma: a Canadian high risk endometrial cancer consortium (CHREC) study. Gynecol Oncol 141:559–563CrossRefPubMed
Metadaten
Titel
Allred score is a promising predictor of prognosis and medroxyprogesterone acetate efficacy in patients with endometrial cancer
Publikationsdatum
24.05.2017
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 1/2017
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-017-3342-5

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