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Erschienen in: Breast Cancer Research and Treatment 2/2011

01.11.2011 | Clinical trial

Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy

verfasst von: Sibylle Loibl, Berit Maria Müller, Gunter von Minckwitz, Michael Schwabe, Marc Roller, Silvia Darb-Esfahani, Beyhan Ataseven, Andreas du Bois, Annette Fissler-Eckhoff, Bernd Gerber, Uwe Kulmer, Jens-Uwe Alles, Keyur Mehta, Carsten Denkert

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2011

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Abstract

The androgen receptor (AR) has been shown to be of potential prognostic importance in retrospective cohorts. We evaluated immunohistochemical AR expression on a tissue microarray of 673 core biopsies from primary breast cancer patients treated with neoadjuvant docetaxel/doxorubicin/cyclophosphamide (TAC) chemotherapy in the prospective GeparTrio phase-III trial. AR was detected in 53.2% of tumours. Lowest AR expression was detected in triple-negative breast cancers (TNBC) with 21.2%. Highest AR expression was observed in Luminal A-like tumours with 67%. In AR-positive tumours, pathological complete response (pCR) rate was 12.8% compared to 25.4% in AR-negative tumours (P < 0.0001). In multivariate analysis, AR independently predicted pCR (OR 1.86; 95% CI [1.16–2.79] P = 0.0086). Overall patients with an AR-positive tumour had a significant better disease-free (DFS) (AR-positive 78.9% vs. AR-negative 72.5%; log-rank P = 0.0329) and overall survival (OS) (88.8% vs. 82.7%; log-rank P = 0.0234) than those with AR-negative tumours. Stratified analysis revealed that in the TNBC subgroup, but not in the other subgroups defined by ER, PgR and HER2, AR expression predicted a better DFS (AR-positive 85.7% vs. AR-negative 65.5% log-rank P = 0.0544) and OS (95.2% vs. 76.2%; log-rank P = 0.0355). Within the non-pCR subgroup, AR positivity selected a group with a significant better DFS (P = 0.045) and OS (0.021) but not within the pCR group. Patients with an AR-negative tumour have a higher chance of achieving a pCR than those with an AR-positive one. But, patients with AR-positive tumours have a better survival especially if they did not achieve a pCR.
Literatur
1.
Zurück zum Zitat Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM et al (2010) Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124:133–140PubMedCrossRef Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM et al (2010) Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124:133–140PubMedCrossRef
2.
Zurück zum Zitat Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple negative breast cancer. N Engl J Med 363(20):1938–1948PubMedCrossRef Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple negative breast cancer. N Engl J Med 363(20):1938–1948PubMedCrossRef
3.
Zurück zum Zitat Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 10:1275–1281 Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 10:1275–1281
4.
Zurück zum Zitat Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC (1996) The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 32:560–1565CrossRef Kuenen-Boumeester V, Van der Kwast TH, Claassen CC, Look MP, Liem GS, Klijn JG, Henzen-Logmans SC (1996) The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters. Eur J Cancer 32:560–1565CrossRef
5.
Zurück zum Zitat Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32PubMedCrossRef Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO (2007) Prognostic markers in triple-negative breast cancer. Cancer 109:25–32PubMedCrossRef
6.
Zurück zum Zitat Ogawa Y, Hai E, Matsumoto K, Ikeda K, Tokunaga S, Nagahara H, Sakurai K, Inoue T, Nishiguchi Y (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers. Int J Clin Oncol 13(5):431–435PubMedCrossRef Ogawa Y, Hai E, Matsumoto K, Ikeda K, Tokunaga S, Nagahara H, Sakurai K, Inoue T, Nishiguchi Y (2008) Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers. Int J Clin Oncol 13(5):431–435PubMedCrossRef
7.
Zurück zum Zitat Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS (2009) Expression of androgen receptor in primary breast cancer. Ann Oncol 21(3):488–492PubMedCrossRef Park S, Koo J, Park HS, Kim JH, Choi SY, Lee JH, Park BW, Lee KS (2009) Expression of androgen receptor in primary breast cancer. Ann Oncol 21(3):488–492PubMedCrossRef
8.
Zurück zum Zitat Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review 2008. J Clin Oncol 26:2568–2581PubMedCrossRef Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review 2008. J Clin Oncol 26:2568–2581PubMedCrossRef
9.
Zurück zum Zitat von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C et al (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551CrossRef von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C et al (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551CrossRef
10.
Zurück zum Zitat von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100:552–562CrossRef von Minckwitz G, Kümmel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100:552–562CrossRef
11.
Zurück zum Zitat Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–140PubMed
12.
Zurück zum Zitat Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H (2003) Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer 98:703–711PubMedCrossRef Moinfar F, Okcu M, Tsybrovskyy O, Regitnig P, Lax SF, Weybora W, Ratschek M, Tavassoli FA, Denk H (2003) Androgen receptors frequently are expressed in breast carcinomas: potential relevance to new therapeutic strategies. Cancer 98:703–711PubMedCrossRef
13.
Zurück zum Zitat Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS et al (2010) Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat 124:607–617PubMedCrossRef Castellano I, Allia E, Accortanzo V, Vandone AM, Chiusa L, Arisio R, Durando A, Donadio M, Bussolati G, Coates AS et al (2010) Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Res Treat 124:607–617PubMedCrossRef
14.
Zurück zum Zitat Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL et al (2009) Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 15:2472–2478PubMedCrossRef Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, Carey M, Agarwal R, Meric-Berstam F, Traina TA, Hudis C, Hortobagyi GN, Gerald WL et al (2009) Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res 15:2472–2478PubMedCrossRef
15.
Zurück zum Zitat Hammond EH, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for immunohistochemical testing of estrogen/progesterone receptors in breast cancer. J Oncol Pract 6(4):195–197PubMedCrossRef Hammond EH, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for immunohistochemical testing of estrogen/progesterone receptors in breast cancer. J Oncol Pract 6(4):195–197PubMedCrossRef
16.
Zurück zum Zitat Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ (2003) Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120:725–731PubMedCrossRef Agoff SN, Swanson PE, Linden H, Hawes SE, Lawton TJ (2003) Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120:725–731PubMedCrossRef
17.
Zurück zum Zitat Micello D, Marando A, Sahname N, Riva C, Capella C, Sessa F (2010) Androgen receptor is frequently expressed in HER2-positive ER/PR-negative breast cancers. Virchows Arch 457:467–476PubMedCrossRef Micello D, Marando A, Sahname N, Riva C, Capella C, Sessa F (2010) Androgen receptor is frequently expressed in HER2-positive ER/PR-negative breast cancers. Virchows Arch 457:467–476PubMedCrossRef
18.
Zurück zum Zitat Luo X, Shi YX, Li ZM, Jiang WQ (2010) Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer 29:585–590PubMed Luo X, Shi YX, Li ZM, Jiang WQ (2010) Expression and clinical significance of androgen receptor in triple negative breast cancer. Chin J Cancer 29:585–590PubMed
19.
Zurück zum Zitat Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, Hudis C, Winer EP (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658–1667PubMedCrossRef Berry DA, Cirrincione C, Henderson IC, Citron ML, Budman DR, Goldstein LJ, Martino S, Perez EA, Muss HB, Norton L, Hudis C, Winer EP (2006) Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658–1667PubMedCrossRef
20.
Zurück zum Zitat Guarneri V, Broglio K, Kau S-W, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN et al (2006) Prognostic value of pathological complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24:1037–1044PubMedCrossRef Guarneri V, Broglio K, Kau S-W, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN et al (2006) Prognostic value of pathological complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24:1037–1044PubMedCrossRef
21.
Zurück zum Zitat He J, Peng R, Yuan Z, Wang S, Peng J, Lin G, Jiang X, Qin T (2011) Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. doi:10.1007/s12032-011-9832-0 He J, Peng R, Yuan Z, Wang S, Peng J, Lin G, Jiang X, Qin T (2011) Prognostic value of androgen receptor expression in operable triple-negative breast cancer: a retrospective analysis based on a tissue microarray. Med Oncol. doi:10.​1007/​s12032-011-9832-0
22.
Zurück zum Zitat Abrial SC, Penault-Llorca F, Delva R, Bougnoux P, Leduc B, Mouret-Reynier MA, Mery-Mignard D, Bleuse JP, Dauplat J, Curé H et al (2005) High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat 94:255–263PubMedCrossRef Abrial SC, Penault-Llorca F, Delva R, Bougnoux P, Leduc B, Mouret-Reynier MA, Mery-Mignard D, Bleuse JP, Dauplat J, Curé H et al (2005) High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat 94:255–263PubMedCrossRef
23.
Zurück zum Zitat Untch M, Fasching PA, Konecny G, Hassmüller S, Lebau A, Kreienberg R, Camara O, Müller V, du Bois A, Kühn T et al (2011) Pathological complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in HER2-overexpressing breast cancer—results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. doi:10.1200/JCO.2010.31.4930 Untch M, Fasching PA, Konecny G, Hassmüller S, Lebau A, Kreienberg R, Camara O, Müller V, du Bois A, Kühn T et al (2011) Pathological complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in HER2-overexpressing breast cancer—results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. doi:10.​1200/​JCO.​2010.​31.​4930
24.
Zurück zum Zitat Gucalp A, Traina TA (2010) Triple-negative breast cancer: role of the androgen receptor. Cancer J 16(1):62–65PubMedCrossRef Gucalp A, Traina TA (2010) Triple-negative breast cancer: role of the androgen receptor. Cancer J 16(1):62–65PubMedCrossRef
25.
Zurück zum Zitat Sapino A, Marchiò C, Senetta R, Castellano I, Macrì L, Cassoni P, Ghisolfi G, Cerrato M, D’Ambrosio E, Bussolati G (2006) Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch 449:288–296PubMedCrossRef Sapino A, Marchiò C, Senetta R, Castellano I, Macrì L, Cassoni P, Ghisolfi G, Cerrato M, D’Ambrosio E, Bussolati G (2006) Routine assessment of prognostic factors in breast cancer using a multicore tissue microarray procedure. Virchows Arch 449:288–296PubMedCrossRef
26.
Zurück zum Zitat Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ (2011) Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol 22(6):1288–1294PubMedCrossRef Yu Q, Niu Y, Liu N, Zhang JZ, Liu TJ, Zhang RJ, Wang SL, Ding XM, Xiao XQ (2011) Expression of androgen receptor in breast cancer and its significance as a prognostic factor. Ann Oncol 22(6):1288–1294PubMedCrossRef
27.
Zurück zum Zitat Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101:736–750PubMedCrossRef Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, Watson M, Davies S, Bernard PS, Parker JS et al (2009) Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 101:736–750PubMedCrossRef
28.
Zurück zum Zitat Voduc KD, Cheang MCU, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691PubMedCrossRef Voduc KD, Cheang MCU, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28:1684–1691PubMedCrossRef
Metadaten
Titel
Androgen receptor expression in primary breast cancer and its predictive and prognostic value in patients treated with neoadjuvant chemotherapy
verfasst von
Sibylle Loibl
Berit Maria Müller
Gunter von Minckwitz
Michael Schwabe
Marc Roller
Silvia Darb-Esfahani
Beyhan Ataseven
Andreas du Bois
Annette Fissler-Eckhoff
Bernd Gerber
Uwe Kulmer
Jens-Uwe Alles
Keyur Mehta
Carsten Denkert
Publikationsdatum
01.11.2011
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2011
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-011-1715-8

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