Skip to main content
Erschienen in: Current Oncology Reports 1/2012

01.02.2012 | Breast Cancer (KR Fox, Section Editor)

Neoadjuvant Clinical Trials for the Treatment of Primary Breast Cancer: The Experience of the German Study Groups

verfasst von: Michael Untch, Sibylle Loibl, Gottfried E. Konecny, Gunter von Minckwitz

Erschienen in: Current Oncology Reports | Ausgabe 1/2012

Einloggen, um Zugang zu erhalten

Abstract

The advantages of neoadjuvant chemotherapy are the ability to 1) increase the rate of breast conservation and improve operability, 2) to reduce mortality by recognizing resistance mechanisms early, and 3) to investigate the activity of new agents by assessing the pathological complete response rate as a surrogate marker for clinical efficacy. The German Breast Group (GBG) is a cooperative study group which focuses on neoadjuvant therapy for breast cancer. This group cooperates closely with the German Gynecological Oncology Working Group—Breast (AGO-B). Additionally, these two German study groups maintain close ties with other national and international study groups, such as the Breast International Group (BIG), Austrian Breast and Colorectal Cancer Study Group (ABCSG), Central European Cooperative Oncology Group (CECOG), International Cooperative Cancer Group (ICCG) and National Surgical Adjuvant Breast Project (NSABP). A series of clinical trials evaluating the role of neoadjuvant therapy in women with primary breast cancer have been designed, performed and published over the last 10 years. This article summarizes the results of the neoadjuvant trials that have been conducted by the German study groups, outlines ongoing clinical research projects, and discusses concepts for future clinical trials.
Literatur
1.
Zurück zum Zitat •• Untch M, Möbus V, Kuhn W, et al.: Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 2009; 27: 2938-2945. This paper shows that intense dose-dense preoperative chemotherapy with epirubicin and paclitaxel is superior to standard chemotherapy in patients with locally advanced breast cancer in terms of local control and overall survival. PubMedCrossRef •• Untch M, Möbus V, Kuhn W, et al.: Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer. J Clin Oncol 2009; 27: 2938-2945. This paper shows that intense dose-dense preoperative chemotherapy with epirubicin and paclitaxel is superior to standard chemotherapy in patients with locally advanced breast cancer in terms of local control and overall survival. PubMedCrossRef
2.
Zurück zum Zitat Untch M, von Minckwitz G, Konecny G, et al.: 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 without CMF ± darbepoetin alfa in primary breast cancer—outcome on prognosis. Ann Oncol 2011;22(9):1999–2006. Untch M, von Minckwitz G, Konecny G, et al.: 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 without CMF ± darbepoetin alfa in primary breast cancer—outcome on prognosis. Ann Oncol 2011;22(9):1999–2006.
3.
Zurück zum Zitat Untch M, Fasching PA, Konecny G, et al.: 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 2011;22:1988–98. Untch M, Fasching PA, Konecny G, et al.: 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 2011;22:1988–98.
4.
Zurück zum Zitat •• Untch M, Fasching PA, Konecny GE, et al.: Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favourable 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 2011; 29:3351–3357. The results of the TECHNO trial support the neoadjuvant use of trastuzumab plus anthracycline and taxane-containing chemotherapy in HER2-positive breast cancer. This therapy leads to a high pCR rate. Patients with a pCR have an improved long-term outcome.PubMedCrossRef •• Untch M, Fasching PA, Konecny GE, et al.: Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favourable 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 2011; 29:3351–3357. The results of the TECHNO trial support the neoadjuvant use of trastuzumab plus anthracycline and taxane-containing chemotherapy in HER2-positive breast cancer. This therapy leads to a high pCR rate. Patients with a pCR have an improved long-term outcome.PubMedCrossRef
5.
Zurück zum Zitat von Minckwitz G, Costa SD, Raab G, et al. 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. 2001;19:3506–15. von Minckwitz G, Costa SD, Raab G, et al. 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. 2001;19:3506–15.
6.
Zurück zum Zitat von Minckwitz G, Raab G, Caputo A, et al. 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. 2005;23:2676–85.CrossRef von Minckwitz G, Raab G, Caputo A, et al. 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. 2005;23:2676–85.CrossRef
7.
Zurück zum Zitat von Minckwitz G, Kümmel S, Vogel P, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008;100:542–51.CrossRef von Minckwitz G, Kümmel S, Vogel P, et al. Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst. 2008;100:542–51.CrossRef
8.
Zurück zum Zitat von Minckwitz G, Kümmel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008;100:552–62.CrossRef von Minckwitz G, Kümmel S, Vogel P, et al. Intensified neoadjuvant chemotherapy in early responding breast cancer: phase III randomized GeparTrio study. J Natl Cancer Inst. 2008;100:552–62.CrossRef
9.
Zurück zum Zitat Huober J, von Minckwitz G, Denkert C, et al. Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010;124:133–40.PubMedCrossRef Huober J, von Minckwitz G, Denkert C, et al. Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010;124:133–40.PubMedCrossRef
10.
Zurück zum Zitat Costa SD, Loibl S, Kaufmann M, et al. Neoadjuvant chemotherapy shows similar response in patients with inflammatory or locally advanced breast cancer when compared with operable breast cancer: A secondary analysis of the GeparTrio trial data. J Clin Oncol. 2010;28:83–91.PubMedCrossRef Costa SD, Loibl S, Kaufmann M, et al. Neoadjuvant chemotherapy shows similar response in patients with inflammatory or locally advanced breast cancer when compared with operable breast cancer: A secondary analysis of the GeparTrio trial data. J Clin Oncol. 2010;28:83–91.PubMedCrossRef
11.
Zurück zum Zitat •• Untch M, Rezai M, Loibl S, et al.: Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: Results from the GeparQuattro study. J Clin Oncol 2010; 28:2024–2031. This trial confirms that combining trastuzumab with anthracycline-taxane–based neoadjuvant chemotherapy results in a high pCR rate without clinically relevant early toxicity and should therefore be considered for patients with HER2-positive disease. PubMedCrossRef •• Untch M, Rezai M, Loibl S, et al.: Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: Results from the GeparQuattro study. J Clin Oncol 2010; 28:2024–2031. This trial confirms that combining trastuzumab with anthracycline-taxane–based neoadjuvant chemotherapy results in a high pCR rate without clinically relevant early toxicity and should therefore be considered for patients with HER2-positive disease. PubMedCrossRef
12.
Zurück zum Zitat von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: Phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRef von Minckwitz G, Rezai M, Loibl S, et al. Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: Phase III GeparQuattro study. J Clin Oncol. 2010;28:2015–23.CrossRef
13.
Zurück zum Zitat von Minckwitz G, Untch M, Nuesch E, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125(1):145–56.CrossRef von Minckwitz G, Untch M, Nuesch E, et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast Cancer Res Treat. 2011;125(1):145–56.CrossRef
14.
Zurück zum Zitat •• von Minckwitz G, Darb-Esfahani S, Loibl S, et al.: Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer-results from the GeparQuattro study (GBG 40). Breast Cancer Res Treat 2011 Jun 12 [Epub ahead of print]. Core biopsies and surgical tissue from patients of the GeparQuattro study before and after neoadjuvant chemotherapy show that HER2-positive invasive ductal carcinomas with adjacent DCIS are less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDSc. HER2 overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression. •• von Minckwitz G, Darb-Esfahani S, Loibl S, et al.: Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer-results from the GeparQuattro study (GBG 40). Breast Cancer Res Treat 2011 Jun 12 [Epub ahead of print]. Core biopsies and surgical tissue from patients of the GeparQuattro study before and after neoadjuvant chemotherapy show that HER2-positive invasive ductal carcinomas with adjacent DCIS are less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDSc. HER2 overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.
15.
Zurück zum Zitat von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al.: for the GBG and AGO-B study groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. NEJM, N Engl J Med 2012;366(4):299–309. von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al.: for the GBG and AGO-B study groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. NEJM, N Engl J Med 2012;366(4):299–309.
16.
Zurück zum Zitat von Minckwitz G, Eidtmann H, Loibl S, et al.: Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial. Ann Oncol 2010;22:301–6. von Minckwitz G, Eidtmann H, Loibl S, et al.: Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial. Ann Oncol 2010;22:301–6.
17.
Zurück zum Zitat Huober J, Hanusch C, Fasching P, Rezai M, Eidtmann H, Kittel K, et al.: for the GBG and AGO-B study groups. Neoadjuvant chemotherapy of paclitaxel with or without Rad001 results of the non-responder part of the GEPARQUINTO study (GBG 44). Cancer Res. 2011;71(24 suppl.):105s. Huober J, Hanusch C, Fasching P, Rezai M, Eidtmann H, Kittel K, et al.: for the GBG and AGO-B study groups. Neoadjuvant chemotherapy of paclitaxel with or without Rad001 results of the non-responder part of the GEPARQUINTO study (GBG 44). Cancer Res. 2011;71(24 suppl.):105s.
18.
Zurück zum Zitat Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer J-U, et al.: for the GBG and AGO-B study group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy: The randomized phase III GEPARQUINTO study (GBG 44). Lancet Oncol, In press, 2012. Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer J-U, et al.: for the GBG and AGO-B study group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy: The randomized phase III GEPARQUINTO study (GBG 44). Lancet Oncol, In press, 2012.
19.
Zurück zum Zitat Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, Aura C, De Azambuja E, et al.: on behalf of the NeoALTTO Study Team. First results of Neo-ALLTO trial: A phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Cancer Res. 2010;70(24 suppl.) Abstr. S3-3 (SABCS 2010). Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, Aura C, De Azambuja E, et al.: on behalf of the NeoALTTO Study Team. First results of Neo-ALLTO trial: A phase III, randomized, open label, neoadjuvant study of lapatinib, trastuzumab, and their combination plus paclitaxel in women with HER2-positive primary breast cancer. Cancer Res. 2010;70(24 suppl.) Abstr. S3-3 (SABCS 2010).
20.
Zurück zum Zitat Loibl S: SOFIA: Phase II study of neoadjuvant epirubicin, cyclophosphamide (EC) plus sorafenib (S) followed by paclitaxel (Pw) plus sorafenib (S) in women with previously untreated primary breast cancer (BC). J Clin Oncol 28: 15s, 2010 (suppl; abstr TPS112) Loibl S: SOFIA: Phase II study of neoadjuvant epirubicin, cyclophosphamide (EC) plus sorafenib (S) followed by paclitaxel (Pw) plus sorafenib (S) in women with previously untreated primary breast cancer (BC). J Clin Oncol 28: 15s, 2010 (suppl; abstr TPS112)
21.
Zurück zum Zitat von Minckwitz G, Kaufmann M, Kuemmel, S, et al,: Correlation of various pathologic complete response (pCR) definitions with long-term outcome and the prognostic value of pCR in various breast cancer subtypes: Results from the German neoadjuvant meta-analysis. J Clin Oncol 29; 2011(suppl; abstr 1028) von Minckwitz G, Kaufmann M, Kuemmel, S, et al,: Correlation of various pathologic complete response (pCR) definitions with long-term outcome and the prognostic value of pCR in various breast cancer subtypes: Results from the German neoadjuvant meta-analysis. J Clin Oncol 29; 2011(suppl; abstr 1028)
Metadaten
Titel
Neoadjuvant Clinical Trials for the Treatment of Primary Breast Cancer: The Experience of the German Study Groups
verfasst von
Michael Untch
Sibylle Loibl
Gottfried E. Konecny
Gunter von Minckwitz
Publikationsdatum
01.02.2012
Verlag
Current Science Inc.
Erschienen in
Current Oncology Reports / Ausgabe 1/2012
Print ISSN: 1523-3790
Elektronische ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-011-0212-x

Weitere Artikel der Ausgabe 1/2012

Current Oncology Reports 1/2012 Zur Ausgabe

Neuro-oncology (M Gilbert, Section Editor)

Radiation Therapy in the Prevention of Brain Metastases

Neuro-oncology (M Gilbert, Section Editor)

Chemoprevention for Brain Metastases

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

16.05.2024 Zielgerichtete Therapie Nachrichten

Trastuzumab deruxtecan scheint auch jenseits von Lungenkrebs gut gegen solide Tumoren mit HER2-Mutationen zu wirken. Dafür sprechen die Daten einer offenen Pan-Tumor-Studie.

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

15.05.2024 Mammakarzinom Nachrichten

Frauen mit lokalem oder metastasiertem Brustkrebs, die Statine einnehmen, haben eine niedrigere krebsspezifische Mortalität als Patientinnen, die dies nicht tun, legen neue Daten aus den USA nahe.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.