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Erschienen in: Breast Cancer Research and Treatment 1/2018

05.09.2017 | Clinical trial

Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials

verfasst von: Marion T. van Mackelenbergh, Carsten Denkert, Valentina Nekljudova, Thomas Karn, Christian Schem, Frederik Marmé, Elmar Stickeler, Christian Jackisch, Claus Hanusch, Jens Huober, Peter A. Fasching, Jens-Uwe Blohmer, Sherko Kümmel, Volkmar Müller, Andreas Schneeweiss, Michael Untch, Gunter von Minckwitz, Karsten E. Weber, Sibylle Loibl

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2018

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Abstract

Purpose

The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome.

Methods

Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression.

Results

The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS.

Conclusion

ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.
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Literatur
1.
Zurück zum Zitat Silva CM, Shupnik MA (2007) Integration of steroid and growth factor pathways in breast cancer: focus on signal transducers and activators of transcription and their potential role in resistance. Mol Endocrinol 21:1499–1512. doi:10.1210/me.2007-0109 CrossRefPubMed Silva CM, Shupnik MA (2007) Integration of steroid and growth factor pathways in breast cancer: focus on signal transducers and activators of transcription and their potential role in resistance. Mol Endocrinol 21:1499–1512. doi:10.​1210/​me.​2007-0109 CrossRefPubMed
2.
Zurück zum Zitat Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E et al (1996) Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J 15:1292–1300PubMedPubMedCentral Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E et al (1996) Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J 15:1292–1300PubMedPubMedCentral
3.
Zurück zum Zitat Dutertre M, Smith CL (2003) Ligand-independent interactions of p160/steroid receptor coactivators and CREB-binding protein (CBP) with estrogen receptor-alpha: regulation by phosphorylation sites in the A/B region depends on other receptor domains. Mol Endocrinol 17:1296–1314CrossRefPubMed Dutertre M, Smith CL (2003) Ligand-independent interactions of p160/steroid receptor coactivators and CREB-binding protein (CBP) with estrogen receptor-alpha: regulation by phosphorylation sites in the A/B region depends on other receptor domains. Mol Endocrinol 17:1296–1314CrossRefPubMed
4.
5.
Zurück zum Zitat Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM (2003) 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. doi:10.1200/JCO.2003.09.099 CrossRefPubMed Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM (2003) 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. doi:10.​1200/​JCO.​2003.​09.​099 CrossRefPubMed
6.
Zurück zum Zitat Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C 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 26:1059–1065. doi:10.1200/JCO.2007.12.9437 CrossRefPubMed Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C 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 26:1059–1065. doi:10.​1200/​JCO.​2007.​12.​9437 CrossRefPubMed
7.
Zurück zum Zitat Viale G, Regan MM, Maiorano E, Mastropasqua MG, Golouh R, Perin T et al (2008) Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors–International Breast Cancer Study Group. J Clin Oncol 26:1404–1410. doi:10.1200/JCO.2007.10.6393 CrossRefPubMed Viale G, Regan MM, Maiorano E, Mastropasqua MG, Golouh R, Perin T et al (2008) Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: predictive value of centrally reviewed expression of estrogen and progesterone receptors–International Breast Cancer Study Group. J Clin Oncol 26:1404–1410. doi:10.​1200/​JCO.​2007.​10.​6393 CrossRefPubMed
8.
Zurück zum Zitat Prat A, Cheang MC, Martin M, Parker JS, Carrasco E, Caballero R et al (2013) Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol 31:203–209. doi:10.1200/JCO.2012.43.4134 CrossRefPubMed Prat A, Cheang MC, Martin M, Parker JS, Carrasco E, Caballero R et al (2013) Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol 31:203–209. doi:10.​1200/​JCO.​2012.​43.​4134 CrossRefPubMed
9.
Zurück zum Zitat von Minckwitz G, Costa SD, Raab G, Blohmer JU, Eidtmann H, Hilfrich J et al (2001) Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol 19:3506–3515CrossRef von Minckwitz G, Costa SD, Raab G, Blohmer JU, Eidtmann H, Hilfrich J et al (2001) Dose-dense doxorubicin, docetaxel, and granulocyte colony-stimulating factor support with or without tamoxifen as preoperative therapy in patients with operable carcinoma of the breast: a randomized, controlled, open phase IIb study. J Clin Oncol 19:3506–3515CrossRef
10.
Zurück zum Zitat von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23:2676–2685. doi:10.1200/JCO.2005.05.078 CrossRef von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU et al (2005) Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 23:2676–2685. doi:10.​1200/​JCO.​2005.​05.​078 CrossRef
11.
Zurück zum Zitat von Minckwitz G, Blohmer JU, Raab G, Lohr A, Gerber B, Heinrich G et al (2005) In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol 16:56–63. doi:10.1093/annonc/mdi001 CrossRef von Minckwitz G, Blohmer JU, Raab G, Lohr A, Gerber B, Heinrich G et al (2005) In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GEPARTRIO pilot study. Ann Oncol 16:56–63. doi:10.​1093/​annonc/​mdi001 CrossRef
12.
Zurück zum Zitat von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100:552–562. doi:10.1093/jnci/djn089 CrossRef von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J et al (2008) Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst 100:552–562. doi:10.​1093/​jnci/​djn089 CrossRef
13.
Zurück zum Zitat von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J et al (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551. doi:10.1093/jnci/djn085 CrossRef von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J et al (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 100:542–551. doi:10.​1093/​jnci/​djn085 CrossRef
14.
15.
Zurück zum Zitat Untch M, Mobus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I et al (2009) Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 27:2938–2945. doi:10.1200/JCO.2008.20.3133 CrossRefPubMed Untch M, Mobus V, Kuhn W, Muck BR, Thomssen C, Bauerfeind I et al (2009) Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 27:2938–2945. doi:10.​1200/​JCO.​2008.​20.​3133 CrossRefPubMed
16.
Zurück zum Zitat Untch M, Fasching PA, Konecny GE, von Koch F, Conrad U, Fett W et al (2011) PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer–results at the time of surgery. Ann Oncol 22:1988–1998. doi:10.1093/annonc/mdq709 CrossRefPubMed Untch M, Fasching PA, Konecny GE, von Koch F, Conrad U, Fett W et al (2011) PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer–results at the time of surgery. Ann Oncol 22:1988–1998. doi:10.​1093/​annonc/​mdq709 CrossRefPubMed
17.
Zurück zum Zitat Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C et al (2011) PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer–outcome on prognosis. Ann Oncol 22:1999–2006. doi:10.1093/annonc/mdq713 CrossRefPubMed Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C et al (2011) PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer–outcome on prognosis. Ann Oncol 22:1999–2006. doi:10.​1093/​annonc/​mdq713 CrossRefPubMed
18.
Zurück zum Zitat Untch M, Fasching PA, Konecny GE, Hasmuller S, Lebeau A, Kreienberg R et al (2011) Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 29:3351–3357. doi:10.1200/JCO.2010.31.4930 CrossRefPubMed Untch M, Fasching PA, Konecny GE, Hasmuller S, Lebeau A, Kreienberg R et al (2011) Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 29:3351–3357. doi:10.​1200/​JCO.​2010.​31.​4930 CrossRefPubMed
19.
Zurück zum Zitat von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S et al (2011) Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125:145–156. doi:10.1007/s10549-010-1228-x CrossRef von Minckwitz G, Untch M, Nuesch E, Loibl S, Kaufmann M, Kummel S et al (2011) Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat 125:145–156. doi:10.​1007/​s10549-010-1228-x CrossRef
20.
Zurück zum Zitat von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366:299–309. doi:10.1056/NEJMoa1111065 CrossRef von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H et al (2012) Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 366:299–309. doi:10.​1056/​NEJMoa1111065 CrossRef
21.
Zurück zum Zitat Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13:135–144. doi:10.1016/S1470-2045(11)70397-7 CrossRefPubMed Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13:135–144. doi:10.​1016/​S1470-2045(11)70397-7 CrossRefPubMed
22.
Zurück zum Zitat von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15:747–756. doi:10.1016/S1470-2045(14)70160-3 CrossRef von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15:747–756. doi:10.​1016/​S1470-2045(14)70160-3 CrossRef
23.
Zurück zum Zitat von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804. doi:10.1200/JCO.2011.38.8595 CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804. doi:10.​1200/​JCO.​2011.​38.​8595 CrossRef
26.
30.
Zurück zum Zitat Grann VR, Troxel AB, Zojwalla NJ, Jacobson JS, Hershman D, Neugut AI (2005) Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer 103:2241–2251. doi:10.1002/cncr.21030 CrossRefPubMed Grann VR, Troxel AB, Zojwalla NJ, Jacobson JS, Hershman D, Neugut AI (2005) Hormone receptor status and survival in a population-based cohort of patients with breast carcinoma. Cancer 103:2241–2251. doi:10.​1002/​cncr.​21030 CrossRefPubMed
31.
Zurück zum Zitat Salmen J, Neugebauer J, Fasching PA, Haeberle L, Huober J, Wockel A et al (2014) Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies. Breast Cancer Res Treat 148:143–151. doi:10.1007/s10549-014-3130-4 CrossRefPubMed Salmen J, Neugebauer J, Fasching PA, Haeberle L, Huober J, Wockel A et al (2014) Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies. Breast Cancer Res Treat 148:143–151. doi:10.​1007/​s10549-014-3130-4 CrossRefPubMed
32.
Zurück zum Zitat Early Breast Cancer Trialists’ Collaborative G, Davies C, Godwin J, Gray R, Clarke M, Cutter D et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784. doi:10.1016/S0140-6736(11)60993-8 CrossRef Early Breast Cancer Trialists’ Collaborative G, Davies C, Godwin J, Gray R, Clarke M, Cutter D et al (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784. doi:10.​1016/​S0140-6736(11)60993-8 CrossRef
33.
Zurück zum Zitat Dowsett M, Houghton J, Iden C, Salter J, Farndon J, A’Hern R et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 17:818–826. doi:10.1093/annonc/mdl016 CrossRefPubMed Dowsett M, Houghton J, Iden C, Salter J, Farndon J, A’Hern R et al (2006) Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 17:818–826. doi:10.​1093/​annonc/​mdl016 CrossRefPubMed
34.
Zurück zum Zitat Viale G, Regan MM, Dell’Orto P, Mastropasqua MG, Maiorano E, Rasmussen BB et al (2011) Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol 22:2201–2207. doi:10.1093/annonc/mdq738 CrossRefPubMedPubMedCentral Viale G, Regan MM, Dell’Orto P, Mastropasqua MG, Maiorano E, Rasmussen BB et al (2011) Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol 22:2201–2207. doi:10.​1093/​annonc/​mdq738 CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Horwitz KB, McGuire WL (1978) Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem 253:2223–2228PubMed Horwitz KB, McGuire WL (1978) Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem 253:2223–2228PubMed
36.
Zurück zum Zitat Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK et al (2005) Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 97:1254–1261. doi:10.1093/jnci/dji249 CrossRefPubMed Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK et al (2005) Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst 97:1254–1261. doi:10.​1093/​jnci/​dji249 CrossRefPubMed
37.
Zurück zum Zitat Arpino G, Wiechmann L, Osborne CK, Schiff R (2008) Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev 29:217–233CrossRefPubMedPubMedCentral Arpino G, Wiechmann L, Osborne CK, Schiff R (2008) Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family: molecular mechanism and clinical implications for endocrine therapy resistance. Endocr Rev 29:217–233CrossRefPubMedPubMedCentral
Metadaten
Titel
Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials
verfasst von
Marion T. van Mackelenbergh
Carsten Denkert
Valentina Nekljudova
Thomas Karn
Christian Schem
Frederik Marmé
Elmar Stickeler
Christian Jackisch
Claus Hanusch
Jens Huober
Peter A. Fasching
Jens-Uwe Blohmer
Sherko Kümmel
Volkmar Müller
Andreas Schneeweiss
Michael Untch
Gunter von Minckwitz
Karsten E. Weber
Sibylle Loibl
Publikationsdatum
05.09.2017
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4480-5

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