Skip to main content
Erschienen in: Breast Cancer Research and Treatment 3/2010

01.12.2010 | Clinical trial

Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival

verfasst von: Sylvia Adams, A. Bapsi Chakravarthy, Martin Donach, Darcy Spicer, Stella Lymberis, Baljit Singh, Joshua A. Bauer, Tsivia Hochman, Judith D. Goldberg, Franco Muggia, Robert J. Schneider, Jennifer A. Pietenpol, Silvia C. Formenti

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2010

Einloggen, um Zugang zu erhalten

Abstract

We have previously demonstrated high pathologic response rates after neoadjuvant concurrent chemoradiation in patients with locally advanced breast cancer (LABC). We now report disease-free survival (DFS) and overall survival (OS) in the context of pathologic response. 105 LABC patients (White 46%, Non-White 54%) were treated with paclitaxel (30 mg/m2 intravenously twice a week) for 10–12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2–7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Pathological complete response (pCR) was defined as the absence of invasive cancer in breast and lymph nodes and pathological partial response (pPR) as the persistence of <10 microscopic foci of invasive carcinoma in breast or lymph nodes. Pathologic response (pCR and pPR) after neoadjuvant chemoradiation was achieved in 36/105 patients (34%) and was associated with significantly better DFS and OS. Pathological responders had a lower risk of recurrence or death (HR = 0.35, P = 0.01) and a longer OS (HR = 4.27, P = 0.01) compared with non-responders. Median DFS and OS were 57 and 84 months for non-responders, respectively, and have not yet been reached for responders. Importantly, pathologic response was achieved in 54% of patients with HR negative tumors (26/48). In conclusion, pathologic response to concurrent paclitaxel-radiation translated into superior DFS and OS. Half of the patients with HR negative tumors achieved a pathologic response.
Literatur
1.
Zurück zum Zitat Feldman LD, Hortobagyi GN, Buzdar AU, Ames FC, Blumenschein GR (1986) Pathological assessment of response to induction chemotherapy in breast cancer. Cancer Res 46(5):2578–2581PubMed Feldman LD, Hortobagyi GN, Buzdar AU, Ames FC, Blumenschein GR (1986) Pathological assessment of response to induction chemotherapy in breast cancer. Cancer Res 46(5):2578–2581PubMed
2.
Zurück zum Zitat Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N (2008) Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols -18 and b-27. J Clin Oncol 26(5):778–785. doi:10.1200/JCO.2007.15.0235 CrossRefPubMed Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N (2008) Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols -18 and b-27. J Clin Oncol 26(5):778–785. doi:10.​1200/​JCO.​2007.​15.​0235 CrossRefPubMed
3.
Zurück zum Zitat Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN (2005) Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23(16):3676–3685. doi:10.1200/JCO.2005.07.032 CrossRefPubMed Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN (2005) Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol 23(16):3676–3685. doi:10.​1200/​JCO.​2005.​07.​032 CrossRefPubMed
4.
Zurück zum Zitat Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN (2007) Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 13(1):228–233. doi:10.1158/1078-0432.CCR-06-1345 Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN (2007) Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res 13(1):228–233. doi:10.​1158/​1078-0432.​CCR-06-1345
5.
Zurück zum Zitat Sikov WM, Dizon DS, Strenger R, Legare RD, Theall KP, Graves TA, Gass JS, Kennedy TA, Fenton MA (2009) Frequent pathologic complete responses in aggressive stages ii to iii breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a brown university oncology group study. J Clin Oncol 27(28):4693–4700. doi:10.1200/JCO.2008.21.4163 CrossRefPubMed Sikov WM, Dizon DS, Strenger R, Legare RD, Theall KP, Graves TA, Gass JS, Kennedy TA, Fenton MA (2009) Frequent pathologic complete responses in aggressive stages ii to iii breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a brown university oncology group study. J Clin Oncol 27(28):4693–4700. doi:10.​1200/​JCO.​2008.​21.​4163 CrossRefPubMed
6.
Zurück zum Zitat Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with her2-positive locally advanced breast cancer (the noah trial): a randomised controlled superiority trial with a parallel her2-negative cohort. Lancet 375(9712):377–384. doi:10.1016/S0140-6736(09)61964-4 Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with her2-positive locally advanced breast cancer (the noah trial): a randomised controlled superiority trial with a parallel her2-negative cohort. Lancet 375(9712):377–384. doi:10.​1016/​S0140-6736(09)61964-4
7.
Zurück zum Zitat Chua S, Smith IE, A’Hern RP, Coombes GA, Hickish TF, Robinson AC, Laing RW, O’Brien ME, Ebbs SR, Hong A, Wardley A, Mughal T, Verrill M, Dubois D, Bliss JM (2005) Neoadjuvant vinorelbine/epirubicin (ve) versus standard adriamycin/cyclophosphamide (ac) in operable breast cancer: analysis of response and tolerability in a randomised phase iii trial (topic 2). Ann Oncol 16(9):1435–1441. doi:10.1093/annonc/mdi276 CrossRefPubMed Chua S, Smith IE, A’Hern RP, Coombes GA, Hickish TF, Robinson AC, Laing RW, O’Brien ME, Ebbs SR, Hong A, Wardley A, Mughal T, Verrill M, Dubois D, Bliss JM (2005) Neoadjuvant vinorelbine/epirubicin (ve) versus standard adriamycin/cyclophosphamide (ac) in operable breast cancer: analysis of response and tolerability in a randomised phase iii trial (topic 2). Ann Oncol 16(9):1435–1441. doi:10.​1093/​annonc/​mdi276 CrossRefPubMed
8.
Zurück zum Zitat Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, Smith TL, Asmar L, Frye D, Manuel N, Kau SW, McNeese M, Strom E, Hunt K, Ames F, Hortobagyi GN (1999) Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 17(11):3412–3417PubMed Buzdar AU, Singletary SE, Theriault RL, Booser DJ, Valero V, Ibrahim N, Smith TL, Asmar L, Frye D, Manuel N, Kau SW, McNeese M, Strom E, Hunt K, Ames F, Hortobagyi GN (1999) Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 17(11):3412–3417PubMed
9.
Zurück zum Zitat Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Mansi JL (2005) Phase iii randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: An anglo-celtic cooperative oncology group study. J Clin Oncol 23(13):2988–2995. doi:10.1200/JCO.2005.06.156 CrossRefPubMed Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, Coleman RE, Perren T, Gallagher CJ, Quigley M, Crown J, Jones AL, Highley M, Leonard RC, Mansi JL (2005) Phase iii randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: An anglo-celtic cooperative oncology group study. J Clin Oncol 23(13):2988–2995. doi:10.​1200/​JCO.​2005.​06.​156 CrossRefPubMed
10.
Zurück zum Zitat Low JA, Berman AW, Steinberg SM, Danforth DN, Lippman ME, Swain SM (2004) Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. J Clin Oncol 22(20):4067–4074. doi:10.1200/JCO.2004.04.068 CrossRefPubMed Low JA, Berman AW, Steinberg SM, Danforth DN, Lippman ME, Swain SM (2004) Long-term follow-up for locally advanced and inflammatory breast cancer patients treated with multimodality therapy. J Clin Oncol 22(20):4067–4074. doi:10.​1200/​JCO.​2004.​04.​068 CrossRefPubMed
11.
Zurück zum Zitat Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20(6):1456–1466CrossRefPubMed Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20(6):1456–1466CrossRefPubMed
12.
Zurück zum Zitat Gradishar WJ, Wedam SB, Jahanzeb M, Erban J, Limentani SA, Tsai KT, Olsen SR, Swain SM (2005) Neoadjuvant docetaxel followed by adjuvant doxorubicin and cyclophosphamide in patients with stage iii breast cancer. Ann Oncol 16(8):1297–1304. doi:10.1093/annonc/mdi254 CrossRefPubMed Gradishar WJ, Wedam SB, Jahanzeb M, Erban J, Limentani SA, Tsai KT, Olsen SR, Swain SM (2005) Neoadjuvant docetaxel followed by adjuvant doxorubicin and cyclophosphamide in patients with stage iii breast cancer. Ann Oncol 16(8):1297–1304. doi:10.​1093/​annonc/​mdi254 CrossRefPubMed
13.
Zurück zum Zitat von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase iii randomized gepartrio trial. J Natl Cancer Inst 100(8):542–551. doi:10.1093/jnci/djn085 CrossRef von Minckwitz G, Kummel S, Vogel P, Hanusch C, Eidtmann H, Hilfrich J, Gerber B, Huober J, Costa SD, Jackisch C, Loibl S, Mehta K, Kaufmann M (2008) Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase iii randomized gepartrio trial. J Natl Cancer Inst 100(8):542–551. doi:10.​1093/​jnci/​djn085 CrossRef
14.
Zurück zum Zitat von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M (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(12):2676–2685. doi:10.1200/JCO.2005.05.078 CrossRef von Minckwitz G, Raab G, Caputo A, Schutte M, Hilfrich J, Blohmer JU, Gerber B, Costa SD, Merkle E, Eidtmann H, Lampe D, Jackisch C, du Bois A, Kaufmann M (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(12):2676–2685. doi:10.​1200/​JCO.​2005.​05.​078 CrossRef
15.
Zurück zum Zitat Burstein HJ, Harris LN, Gelman R, Lester SC, Nunes RA, Kaelin CM, Parker LM, Ellisen LW, Kuter I, Gadd MA, Christian RL, Kennedy PR, Borges VF, Bunnell CA, Younger J, Smith BL, Winer EP (2003) Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for her2 overexpressing stage ii or iii breast cancer: a pilot study. J Clin Oncol 21(1):46–53CrossRefPubMed Burstein HJ, Harris LN, Gelman R, Lester SC, Nunes RA, Kaelin CM, Parker LM, Ellisen LW, Kuter I, Gadd MA, Christian RL, Kennedy PR, Borges VF, Bunnell CA, Younger J, Smith BL, Winer EP (2003) Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for her2 overexpressing stage ii or iii breast cancer: a pilot study. J Clin Oncol 21(1):46–53CrossRefPubMed
16.
Zurück zum Zitat Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN (2005) Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 23(25):5983–5992. doi:10.1200/JCO.2005.06.232 CrossRefPubMed Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN (2005) Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 23(25):5983–5992. doi:10.​1200/​JCO.​2005.​06.​232 CrossRefPubMed
17.
Zurück zum Zitat Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM (2006) Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24(7):1037–1044. doi:10.1200/JCO.2005.02.6914 CrossRefPubMed Guarneri V, Broglio K, Kau SW, Cristofanilli M, Buzdar AU, Valero V, Buchholz T, Meric F, Middleton L, Hortobagyi GN, Gonzalez-Angulo AM (2006) Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol 24(7):1037–1044. doi:10.​1200/​JCO.​2005.​02.​6914 CrossRefPubMed
18.
Zurück zum Zitat Colleoni M, Nole F, Minchella I, Noberasco C, Luini A, Orecchia R, Veronesi P, Zurrida S, Viale G, Goldhirsch A (1998) Pre-operative chemotherapy and radiotherapy in breast cancer. Eur J Cancer 34(5):641–645CrossRefPubMed Colleoni M, Nole F, Minchella I, Noberasco C, Luini A, Orecchia R, Veronesi P, Zurrida S, Viale G, Goldhirsch A (1998) Pre-operative chemotherapy and radiotherapy in breast cancer. Eur J Cancer 34(5):641–645CrossRefPubMed
19.
Zurück zum Zitat Lorvidhaya V, Chitapanarux I, Sangruchi S, Lertsanguansinchai P, Kongthanarat Y, Tangkaratt S, Visetsiri E (2003) Concurrent mitomycin c, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. Int j Radiat Oncol Biol Phys 55(5):1226–1232PubMed Lorvidhaya V, Chitapanarux I, Sangruchi S, Lertsanguansinchai P, Kongthanarat Y, Tangkaratt S, Visetsiri E (2003) Concurrent mitomycin c, 5-fluorouracil, and radiotherapy in the treatment of locally advanced carcinoma of the cervix: a randomized trial. Int j Radiat Oncol Biol Phys 55(5):1226–1232PubMed
20.
Zurück zum Zitat Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, Kubik A, Krepela E, Fiala P, Pecen L (2004) Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 46(1):87–98. doi:10.1016/j.lungcan.2004.03.004 CrossRefPubMed Zatloukal P, Petruzelka L, Zemanova M, Havel L, Janku F, Judas L, Kubik A, Krepela E, Fiala P, Pecen L (2004) Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 46(1):87–98. doi:10.​1016/​j.​lungcan.​2004.​03.​004 CrossRefPubMed
21.
Zurück zum Zitat Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N (2002) Phase iii study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin, etoposide for limited-stage small-cell lung cancer: results of the japan clinical oncology group study 9104. J Clin Oncol 20(14):3054–3060CrossRefPubMed Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N (2002) Phase iii study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin, etoposide for limited-stage small-cell lung cancer: results of the japan clinical oncology group study 9104. J Clin Oncol 20(14):3054–3060CrossRefPubMed
22.
Zurück zum Zitat Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y (1999) Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 17(9):2692–2699PubMed Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y (1999) Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 17(9):2692–2699PubMed
23.
Zurück zum Zitat Kwong DL, Sham JS, Au GK, Chua DT, Kwong PW, Cheng AC, Wu PM, Law MW, Kwok CC, Yau CC, Wan KY, Chan RT, Choy DD (2004) Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol 22(13):2643–2653. doi:10.1200/JCO.2004.05.173 CrossRefPubMed Kwong DL, Sham JS, Au GK, Chua DT, Kwong PW, Cheng AC, Wu PM, Law MW, Kwok CC, Yau CC, Wan KY, Chan RT, Choy DD (2004) Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study. J Clin Oncol 22(13):2643–2653. doi:10.​1200/​JCO.​2004.​05.​173 CrossRefPubMed
24.
Zurück zum Zitat Formenti SC, Volm M, Skinner KA, Spicer D, Cohen D, Perez E, Bettini AC, Groshen S, Gee C, Florentine B, Press M, Danenberg P, Muggia F (2003) Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol 21(5):864–870CrossRefPubMed Formenti SC, Volm M, Skinner KA, Spicer D, Cohen D, Perez E, Bettini AC, Groshen S, Gee C, Florentine B, Press M, Danenberg P, Muggia F (2003) Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial. J Clin Oncol 21(5):864–870CrossRefPubMed
25.
Zurück zum Zitat Chakravarthy AB, Kelley MC, McLaren B, Truica CI, Billheimer D, Mayer IA, Grau AM, Johnson DH, Simpson JF, Beauchamp RD, Jones C, Pietenpol JA (2006) Neoadjuvant concurrent paclitaxel and radiation in stage II/III breast cancer. Clin Cancer Res 12(5):1570–1576. doi:10.1158/1078-0432.CCR-05-2304 CrossRefPubMed Chakravarthy AB, Kelley MC, McLaren B, Truica CI, Billheimer D, Mayer IA, Grau AM, Johnson DH, Simpson JF, Beauchamp RD, Jones C, Pietenpol JA (2006) Neoadjuvant concurrent paclitaxel and radiation in stage II/III breast cancer. Clin Cancer Res 12(5):1570–1576. doi:10.​1158/​1078-0432.​CCR-05-2304 CrossRefPubMed
26.
Zurück zum Zitat Formenti SC, Dunnington G, Uzieli B, Lenz H, Keren-Rosenberg S, Silberman H, Spicer D, Denk M, Leichman G, Groshen S, Watkins K, Muggia F, Florentine B, Press M, Danenberg K, Danenberg P (1997) Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. Int J Radiat Oncol Biol Phys 39(5):1059–1068PubMed Formenti SC, Dunnington G, Uzieli B, Lenz H, Keren-Rosenberg S, Silberman H, Spicer D, Denk M, Leichman G, Groshen S, Watkins K, Muggia F, Florentine B, Press M, Danenberg K, Danenberg P (1997) Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. Int J Radiat Oncol Biol Phys 39(5):1059–1068PubMed
28.
Zurück zum Zitat Yerushalmi R, Hayes MM, Gelmon KA, Chia S, Bajdik C, Norris B, Speers C, Hassell P, O’Reilly SE, Allan S, Shenkier TN (2009) A phase II trial of a neoadjuvant platinum regimen for locally advanced breast cancer: pathologic response, long-term follow-up, and correlation with biomarkers. Clin Breast Cancer 9(3):166–172. doi:10.3816/CBC.2009.n.027 CrossRefPubMed Yerushalmi R, Hayes MM, Gelmon KA, Chia S, Bajdik C, Norris B, Speers C, Hassell P, O’Reilly SE, Allan S, Shenkier TN (2009) A phase II trial of a neoadjuvant platinum regimen for locally advanced breast cancer: pathologic response, long-term follow-up, and correlation with biomarkers. Clin Breast Cancer 9(3):166–172. doi:10.​3816/​CBC.​2009.​n.​027 CrossRefPubMed
29.
Zurück zum Zitat Moon YW, Rha SY, Jeung HC, Yang WI, Suh CO, Chung HC (2005) Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and cyclophosphamide (ifac) in locally advanced breast cancer: an early response predicts good prognosis. Ann Oncol 16(11):1778–1785. doi:10.1093/annonc/mdi360 CrossRefPubMed Moon YW, Rha SY, Jeung HC, Yang WI, Suh CO, Chung HC (2005) Neoadjuvant chemotherapy with infusional 5-fluorouracil, adriamycin and cyclophosphamide (ifac) in locally advanced breast cancer: an early response predicts good prognosis. Ann Oncol 16(11):1778–1785. doi:10.​1093/​annonc/​mdi360 CrossRefPubMed
30.
Zurück zum Zitat Schwartz GF, Birchansky CA, Komarnicky LT, Mansfield CM, Cantor RI, Biermann WA, Fellin FM, McFarlane J (1994) Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer 73(2):362–369CrossRefPubMed Schwartz GF, Birchansky CA, Komarnicky LT, Mansfield CM, Cantor RI, Biermann WA, Fellin FM, McFarlane J (1994) Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer 73(2):362–369CrossRefPubMed
31.
Zurück zum Zitat Zambetti M, Oriana S, Quattrone P, Verderio P, Terenziani M, Zucali R, Valagussa P, Bonadonna G (1999) Combined sequential approach in locally advanced breast cancer. Ann Oncol 10(3):305–310CrossRefPubMed Zambetti M, Oriana S, Quattrone P, Verderio P, Terenziani M, Zucali R, Valagussa P, Bonadonna G (1999) Combined sequential approach in locally advanced breast cancer. Ann Oncol 10(3):305–310CrossRefPubMed
32.
Zurück zum Zitat Frasci G, D’Aiuto G, Comella P, D’Aiuto M, Di Bonito M, Ruffolo P, Iodice G, Petrillo A, Lastoria S, Oliviero P, Capasso I, Montella M, Siani C, Santangelo M, Vizioli L, Comella G (2009) Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908. Ann Oncol. doi:10.1093/annonc/mdp356 Frasci G, D’Aiuto G, Comella P, D’Aiuto M, Di Bonito M, Ruffolo P, Iodice G, Petrillo A, Lastoria S, Oliviero P, Capasso I, Montella M, Siani C, Santangelo M, Vizioli L, Comella G (2009) Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908. Ann Oncol. doi:10.​1093/​annonc/​mdp356
33.
Zurück zum Zitat Alvarez RH, Booser DJ, Cristofanilli M, Sahin AA, Strom EA, Guerra L, Kau SW, Gonzalez-Angulo AM, Hortobagyi GN, Valero V (2010) Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer: long-term results from the University of Texas M. D. Anderson Cancer Center Study id97-099. Cancer 116(5):1210–1217. doi:10.1002/cncr.24901 Alvarez RH, Booser DJ, Cristofanilli M, Sahin AA, Strom EA, Guerra L, Kau SW, Gonzalez-Angulo AM, Hortobagyi GN, Valero V (2010) Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer: long-term results from the University of Texas M. D. Anderson Cancer Center Study id97-099. Cancer 116(5):1210–1217. doi:10.​1002/​cncr.​24901
34.
Zurück zum Zitat Ezzat AA, Ibrahim EM, Ajarim DS, Rahal MM, Raja MA, Tulbah AM, Al-Malik OA, Al-Shabanah M, Sorbris R (2004) Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients. Br J Cancer 90(5):968–974. doi:10.1038/sj.bjc.6601616 CrossRefPubMed Ezzat AA, Ibrahim EM, Ajarim DS, Rahal MM, Raja MA, Tulbah AM, Al-Malik OA, Al-Shabanah M, Sorbris R (2004) Phase II study of neoadjuvant paclitaxel and cisplatin for operable and locally advanced breast cancer: analysis of 126 patients. Br J Cancer 90(5):968–974. doi:10.​1038/​sj.​bjc.​6601616 CrossRefPubMed
35.
Zurück zum Zitat Carey LA, Metzger R, Dees EC, Collichio F, Sartor CI, Ollila DW, Klauber-DeMore N, Halle J, Sawyer L, Moore DT, Graham ML (2005) American joint committee on cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 97(15):1137–1142. doi:10.1093/jnci/dji206 CrossRefPubMed Carey LA, Metzger R, Dees EC, Collichio F, Sartor CI, Ollila DW, Klauber-DeMore N, Halle J, Sawyer L, Moore DT, Graham ML (2005) American joint committee on cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 97(15):1137–1142. doi:10.​1093/​jnci/​dji206 CrossRefPubMed
36.
Zurück zum Zitat Bonadonna G, Valagussa P, Brambilla C, Ferrari L, Moliterni A, Terenziani M, Zambetti M (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16(1):93–100PubMed Bonadonna G, Valagussa P, Brambilla C, Ferrari L, Moliterni A, Terenziani M, Zambetti M (1998) Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol 16(1):93–100PubMed
37.
Zurück zum Zitat Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685PubMed Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD (1998) Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16(8):2672–2685PubMed
38.
Zurück zum Zitat Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25(28):4414–4422. doi:10.1200/JCO.2007.10.6823 CrossRefPubMed Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L (2007) Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 25(28):4414–4422. doi:10.​1200/​JCO.​2007.​10.​6823 CrossRefPubMed
39.
Zurück zum Zitat Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17(2):460–469PubMed Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE (1999) Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17(2):460–469PubMed
40.
Zurück zum Zitat Cance WG, Carey LA, Calvo BF, Sartor C, Sawyer L, Moore DT, Rosenman J, Ollila DW, Graham M 2nd (2002) Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma: effective clinical downstaging allows breast preservation and predicts outstanding local control and survival. Ann Surg 236(3):295–302. doi:10.1097/01.SLA.0000027526.67560.64 discussion 302–303CrossRefPubMed Cance WG, Carey LA, Calvo BF, Sartor C, Sawyer L, Moore DT, Rosenman J, Ollila DW, Graham M 2nd (2002) Long-term outcome of neoadjuvant therapy for locally advanced breast carcinoma: effective clinical downstaging allows breast preservation and predicts outstanding local control and survival. Ann Surg 236(3):295–302. doi:10.​1097/​01.​SLA.​0000027526.​67560.​64 discussion 302–303CrossRefPubMed
41.
Zurück zum Zitat AJCC cancer staging manual (2010). 7th edn. Springer AJCC cancer staging manual (2010). 7th edn. Springer
42.
Zurück zum Zitat Shanta V, Swaminathan R, Rama R, Radhika R (2008) Retrospective analysis of locally advanced noninflammatory breast cancer from chennai, South India, 1990–1999. Int J Radiat Oncol Biol Phys 70(1):51–58. doi:10.1016/j.ijrobp.2007.05.050 PubMed Shanta V, Swaminathan R, Rama R, Radhika R (2008) Retrospective analysis of locally advanced noninflammatory breast cancer from chennai, South India, 1990–1999. Int J Radiat Oncol Biol Phys 70(1):51–58. doi:10.​1016/​j.​ijrobp.​2007.​05.​050 PubMed
43.
Zurück zum Zitat Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334. doi:10.1158/1078-0432.CCR-06-1109 CrossRefPubMed Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334. doi:10.​1158/​1078-0432.​CCR-06-1109 CrossRefPubMed
44.
Zurück zum Zitat Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281. doi:10.1200/JCO.2007.14.4147 CrossRefPubMed Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, Cristofanilli M, Hortobagyi GN, Pusztai L (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281. doi:10.​1200/​JCO.​2007.​14.​4147 CrossRefPubMed
45.
Zurück zum Zitat Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16):5678–5685. doi:10.1158/1078-0432.CCR-04-2421 CrossRefPubMed Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11(16):5678–5685. doi:10.​1158/​1078-0432.​CCR-04-2421 CrossRefPubMed
47.
Zurück zum Zitat Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106(33):13820–13825. doi:10.1073/pnas.0905718106 CrossRefPubMed Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC (2009) Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 106(33):13820–13825. doi:10.​1073/​pnas.​0905718106 CrossRefPubMed
49.
Zurück zum Zitat Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA, Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli RM, Pietenpol JA (2010) Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin Cancer Res 16(2):681–690. doi:10.1158/1078-0432.CCR-09-1091 CrossRefPubMed Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, De Matos Granja-Ingram N, Olivares MG, Kelley MC, Mayer IA, Meszoely IM, Means-Powell JA, Johnson KN, Tsai CJ, Ayers GD, Sanders ME, Schneider RJ, Formenti SC, Caprioli RM, Pietenpol JA (2010) Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin Cancer Res 16(2):681–690. doi:10.​1158/​1078-0432.​CCR-09-1091 CrossRefPubMed
50.
Zurück zum Zitat Nishio K, Arioka H, Ishida T, Fukumoto H, Kurokawa H, Sata M, Ohata M, Saijo N (1995) Enhanced interaction between tubulin and microtubule-associated protein 2 via inhibition of map kinase and cdc2 kinase by paclitaxel. Int J Cancer 63(5):688–693CrossRefPubMed Nishio K, Arioka H, Ishida T, Fukumoto H, Kurokawa H, Sata M, Ohata M, Saijo N (1995) Enhanced interaction between tubulin and microtubule-associated protein 2 via inhibition of map kinase and cdc2 kinase by paclitaxel. Int J Cancer 63(5):688–693CrossRefPubMed
52.
Zurück zum Zitat Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9(5):R65. doi:10.1186/bcr1771 CrossRefPubMed Kreike B, van Kouwenhove M, Horlings H, Weigelt B, Peterse H, Bartelink H, van de Vijver MJ (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9(5):R65. doi:10.​1186/​bcr1771 CrossRefPubMed
53.
Zurück zum Zitat Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13(9):1050–1059. doi:10.1038/nm1622 CrossRefPubMed Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, Mignot G, Maiuri MC, Ullrich E, Saulnier P, Yang H, Amigorena S, Ryffel B, Barrat FJ, Saftig P, Levi F, Lidereau R, Nogues C, Mira JP, Chompret A, Joulin V, Clavel-Chapelon F, Bourhis J, Andre F, Delaloge S, Tursz T, Kroemer G, Zitvogel L (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13(9):1050–1059. doi:10.​1038/​nm1622 CrossRefPubMed
56.
Zurück zum Zitat Formenti SC (2010) Immunological aspects of local radiotherapy: clinical relevance. Discov Med 9(45):119–124PubMed Formenti SC (2010) Immunological aspects of local radiotherapy: clinical relevance. Discov Med 9(45):119–124PubMed
57.
Metadaten
Titel
Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival
verfasst von
Sylvia Adams
A. Bapsi Chakravarthy
Martin Donach
Darcy Spicer
Stella Lymberis
Baljit Singh
Joshua A. Bauer
Tsivia Hochman
Judith D. Goldberg
Franco Muggia
Robert J. Schneider
Jennifer A. Pietenpol
Silvia C. Formenti
Publikationsdatum
01.12.2010
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2010
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1181-8

Weitere Artikel der Ausgabe 3/2010

Breast Cancer Research and Treatment 3/2010 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

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