Skip to main content
Erschienen in: Journal of Neuro-Oncology 3/2007

01.12.2007 | Clinical-Patient Studies

Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer

verfasst von: Rupert Bartsch, Andrea Rottenfusser, Catharina Wenzel, Karin Dieckmann, Ursula Pluschnig, Gabriela Altorjai, Margaretha Rudas, Robert M. Mader, Richard Poetter, Christoph C. Zielinski, Guenther G. Steger

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2007

Einloggen, um Zugang zu erhalten

Abstract

Background: Brain metastases are frequently encountered in Her2 positive advanced breast cancer. It is still not clear, if trastuzumab treatment should be continued following their diagnosis. In this analysis we evaluated if trastuzumab was able to influence time to in-brain progression (TTP) and overall survival (OS). For this reason, we compared patients who continued on trastuzumab with a historical control group. Patients and Methods: Seventeen Her2 positive patients receiving whole brain radiotherapy for brain metastases and continuing on trastuzumab were identified. As historical control group, thirty-six patients treated before 2002 were identified from a breast cancer database. We performed a multivariate analysis (Cox regression) to explore which factors were potentially able to significantly influence TTP and OS. Results: Median TTP was 6 months, range 1–33+ months. Median OS was 7 months, range 1–38 months. Seventeen patients received trastuzumab after WBRT. Factors associated with prolonged TTP were KPS (p = 0.001), and intensified local treatment (p = 0.004). A trend towards longer TTP was observed in patients treated with trastuzumab (p = 0.068). OS was significantly influenced by KPS (p < 0.001), and continued antibody therapy (p = 0.001). Conclusion: Two parameters were significantly associated with prolonged OS: KPS and trastuzumab. While there was a trend towards prolonged TTP in patients with trastuzumab treatment after WBRT, this did not reach statistical significance. It appears therefore reasonable to suggest continuation of antibody therapy in patients with good performance status despite disease spreading to the brain. Concerning activity of trastuzumab in brain metastases themselves, no final conclusion is possible.
Literatur
1.
Zurück zum Zitat Boyle P, Ferlay J (2005) Cancer incidence and mortality in Europe, 2004. Ann Oncol 16:481–488PubMedCrossRef Boyle P, Ferlay J (2005) Cancer incidence and mortality in Europe, 2004. Ann Oncol 16:481–488PubMedCrossRef
2.
Zurück zum Zitat Smigal C, Jemal A, Ward E et al (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56:168–183PubMed Smigal C, Jemal A, Ward E et al (2006) Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin 56:168–183PubMed
3.
Zurück zum Zitat Mollick JA, Carlson RW (2004) Rational surveillance programs for early stage breast cancer patients after primary treatment. Breast Dis 21:47–54PubMed Mollick JA, Carlson RW (2004) Rational surveillance programs for early stage breast cancer patients after primary treatment. Breast Dis 21:47–54PubMed
4.
Zurück zum Zitat Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science (Wash. DC) 235:177–182CrossRef Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science (Wash. DC) 235:177–182CrossRef
5.
Zurück zum Zitat Boss JS, Fletcher JA, Linette GP (2003) The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 8:307–325CrossRef Boss JS, Fletcher JA, Linette GP (2003) The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist 8:307–325CrossRef
6.
Zurück zum Zitat Paik S, Hazan R, Fisher ER et al (1990) Pathologic finding from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein expression in primary breast cancer. J Clin Oncol 8:103–112PubMed Paik S, Hazan R, Fisher ER et al (1990) Pathologic finding from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein expression in primary breast cancer. J Clin Oncol 8:103–112PubMed
7.
Zurück zum Zitat Kallioniemi OP, Holli K, Visakorpi T et al (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 4:650–655CrossRef Kallioniemi OP, Holli K, Visakorpi T et al (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 4:650–655CrossRef
8.
Zurück zum Zitat Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRef
9.
Zurück zum Zitat Pegram MD, Konecny GE, O´Callaghan C et al (2004) Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst 96:739–749PubMedCrossRef Pegram MD, Konecny GE, O´Callaghan C et al (2004) Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J Natl Cancer Inst 96:739–749PubMedCrossRef
10.
Zurück zum Zitat Clynes RA, Towers TL, Presta LG et al (2006) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443 Clynes RA, Towers TL, Presta LG et al (2006) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443
11.
Zurück zum Zitat Nahta R, Yu D, Hung MC et al (2006) Mechanisms of Disease: Understanding resistance to Her2-targeted therapy in human breast cancer. Nat Clin Practice Oncol 3:269–280CrossRef Nahta R, Yu D, Hung MC et al (2006) Mechanisms of Disease: Understanding resistance to Her2-targeted therapy in human breast cancer. Nat Clin Practice Oncol 3:269–280CrossRef
12.
Zurück zum Zitat Bendell JC, Domchek SM, Burstein HJ et al (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977PubMedCrossRef Bendell JC, Domchek SM, Burstein HJ et al (2003) Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 97:2972–2977PubMedCrossRef
13.
Zurück zum Zitat Clayton AJ, Danson S, Jolly S et al (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643PubMed Clayton AJ, Danson S, Jolly S et al (2004) Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer. Br J Cancer 91:639–643PubMed
14.
Zurück zum Zitat Shmueli E, Wigler N, Inbar M (2004) Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 40:379–382PubMedCrossRef Shmueli E, Wigler N, Inbar M (2004) Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. Eur J Cancer 40:379–382PubMedCrossRef
15.
Zurück zum Zitat Herrero A, Grandez R, Puertolas T et al (2004) High incidence of brain metastases at the time of death in women with metastatic breast cancer treated with trastuzumab. J Clin Oncol 22(suppl 14):765s Herrero A, Grandez R, Puertolas T et al (2004) High incidence of brain metastases at the time of death in women with metastatic breast cancer treated with trastuzumab. J Clin Oncol 22(suppl 14):765s
16.
Zurück zum Zitat DiStefano A, Yong Yap Y, Hortobagyii GN et al (1979) The natural history of breast cancer patients with brain metastases. Cancer 44:1913–1918PubMedCrossRef DiStefano A, Yong Yap Y, Hortobagyii GN et al (1979) The natural history of breast cancer patients with brain metastases. Cancer 44:1913–1918PubMedCrossRef
17.
Zurück zum Zitat Lagerwaard FJ, Levendag PC, Nowak PJ et al (1999) Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43:795–803PubMedCrossRef Lagerwaard FJ, Levendag PC, Nowak PJ et al (1999) Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 43:795–803PubMedCrossRef
18.
Zurück zum Zitat Mahmoud-Ahmed AS, Duh JH, Lee SY et al (2002) Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study. Int J Radiat Oncol Biol Phys 54:810–817PubMedCrossRef Mahmoud-Ahmed AS, Duh JH, Lee SY et al (2002) Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study. Int J Radiat Oncol Biol Phys 54:810–817PubMedCrossRef
19.
20.
Zurück zum Zitat Fokstuen T, Wilking N, Rutqvist LE et al (2000) Radiation therapy in the management of brain metastases from breast cancer. Breast Cancer Res Treat 62:211–216PubMedCrossRef Fokstuen T, Wilking N, Rutqvist LE et al (2000) Radiation therapy in the management of brain metastases from breast cancer. Breast Cancer Res Treat 62:211–216PubMedCrossRef
21.
Zurück zum Zitat Hendrickson FR, Lee MS, Larson M et al (1983) The influence of surgery and radiation therapy on patients with brain metastases. In J Radiat Oncol Biol Phys 9:623–627CrossRef Hendrickson FR, Lee MS, Larson M et al (1983) The influence of surgery and radiation therapy on patients with brain metastases. In J Radiat Oncol Biol Phys 9:623–627CrossRef
22.
Zurück zum Zitat Bindal RK, Samaya R, Leavens ME et al (1993) Surgical treatment of multiple brain metastases. J Neurosurg 79:210–216PubMed Bindal RK, Samaya R, Leavens ME et al (1993) Surgical treatment of multiple brain metastases. J Neurosurg 79:210–216PubMed
23.
Zurück zum Zitat Borgelt B, Gelber R, Kramer S et al (1980) The palliation of brain metastases: Final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 6:1–9PubMed Borgelt B, Gelber R, Kramer S et al (1980) The palliation of brain metastases: Final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 6:1–9PubMed
24.
Zurück zum Zitat Lohr F, Pirzkall A, Hof H et al (2001) Adjuvant treatment of brain metastases. Semin Surg Oncol 20:50–56PubMedCrossRef Lohr F, Pirzkall A, Hof H et al (2001) Adjuvant treatment of brain metastases. Semin Surg Oncol 20:50–56PubMedCrossRef
25.
Zurück zum Zitat Sneed PK, Larson DA, Wara WM (1996) Radiotherapy for cerebral metastases. Neurosurg Clin N Am 7:505–515PubMed Sneed PK, Larson DA, Wara WM (1996) Radiotherapy for cerebral metastases. Neurosurg Clin N Am 7:505–515PubMed
26.
Zurück zum Zitat Broadbent AM, Hruby G, Tin MM et al (2004) Survival following whole brain radiation treatment for cerebral metastases: an audit of 747 patients. Radiother Oncol 71:259–265PubMedCrossRef Broadbent AM, Hruby G, Tin MM et al (2004) Survival following whole brain radiation treatment for cerebral metastases: an audit of 747 patients. Radiother Oncol 71:259–265PubMedCrossRef
27.
Zurück zum Zitat Lutterbach J, Bartelt S, Stancu E et al (2002) Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3. Radiother Oncol 263:399–345 Lutterbach J, Bartelt S, Stancu E et al (2002) Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3. Radiother Oncol 263:399–345
28.
Zurück zum Zitat Shaw E, Scott C, Souhami L et al (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumours and brain metastases: final report of RTOG protocol 90–05. Int J Radiat Oncol Biol Phys 47:291–298PubMedCrossRef Shaw E, Scott C, Souhami L et al (2000) Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumours and brain metastases: final report of RTOG protocol 90–05. Int J Radiat Oncol Biol Phys 47:291–298PubMedCrossRef
29.
Zurück zum Zitat Loeffler JS, Kooy HM, Wen PY et al (1990) The treatment of recurrent brain metastases with stereotactic radiosurgery. J Clin Oncol 8:576–582PubMed Loeffler JS, Kooy HM, Wen PY et al (1990) The treatment of recurrent brain metastases with stereotactic radiosurgery. J Clin Oncol 8:576–582PubMed
30.
Zurück zum Zitat Lederman G, Wronski M, Fine M (2001) Fractionated radiosurgery for brain metastases in 43 patients with breast carcinoma. Breast Cancer Res Treat 65:145–154PubMedCrossRef Lederman G, Wronski M, Fine M (2001) Fractionated radiosurgery for brain metastases in 43 patients with breast carcinoma. Breast Cancer Res Treat 65:145–154PubMedCrossRef
31.
Zurück zum Zitat Noel G, Simon JM, Valery CA et al (2003) Radiosurgery for brain metastasis: impact of CTV on local control. Radiother Oncol 2068:15–21CrossRef Noel G, Simon JM, Valery CA et al (2003) Radiosurgery for brain metastasis: impact of CTV on local control. Radiother Oncol 2068:15–21CrossRef
32.
Zurück zum Zitat Becker G, Jeremic B, Engel C et al (2002) Radiosurgery for brain metastases: the Tuebingen experience. Radiother Oncol 62:233–237PubMedCrossRef Becker G, Jeremic B, Engel C et al (2002) Radiosurgery for brain metastases: the Tuebingen experience. Radiother Oncol 62:233–237PubMedCrossRef
33.
Zurück zum Zitat Lower EE, Dosick DR, Blau R et al (2003) Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer 4:114–119PubMedCrossRef Lower EE, Dosick DR, Blau R et al (2003) Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival. Clin Breast Cancer 4:114–119PubMedCrossRef
34.
Zurück zum Zitat Kirsch DG, Ledezma CJ, Mathews CS et al (2005) Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 39:2114–2116CrossRef Kirsch DG, Ledezma CJ, Mathews CS et al (2005) Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 39:2114–2116CrossRef
35.
Zurück zum Zitat Leyland-Jones B, Gelmon K, Ayoub JP et al (2003) Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 21:3965–3971PubMedCrossRef Leyland-Jones B, Gelmon K, Ayoub JP et al (2003) Pharmacokinetics, safety, and efficacy of trastuzumab administered every three weeks in combination with paclitaxel. J Clin Oncol 21:3965–3971PubMedCrossRef
36.
Zurück zum Zitat Fazeny-Dorner B, Wenzel C, Veitl M et al (2003) Survival and prognostic factors of patients with unresectable glioblastoma multiforme. Anticancer Drugs 14:305–312PubMedCrossRef Fazeny-Dorner B, Wenzel C, Veitl M et al (2003) Survival and prognostic factors of patients with unresectable glioblastoma multiforme. Anticancer Drugs 14:305–312PubMedCrossRef
37.
Zurück zum Zitat Fernandez-Vicioso E, Suh JH, Kupelian PA et al (1997) Analysis of prognostic factors for patients with single brain metastases treated with stereotactic radiosurgery. Radiat Oncol Investig 5:31–37PubMedCrossRef Fernandez-Vicioso E, Suh JH, Kupelian PA et al (1997) Analysis of prognostic factors for patients with single brain metastases treated with stereotactic radiosurgery. Radiat Oncol Investig 5:31–37PubMedCrossRef
38.
Zurück zum Zitat Serizawa T, Saeki N, Higuchi Y et al (2005) Gamma knife surgery for brain metastases: indications for and limitations of a local treatment protocol. Acta Neurochir (Wien) 147:721–726CrossRef Serizawa T, Saeki N, Higuchi Y et al (2005) Gamma knife surgery for brain metastases: indications for and limitations of a local treatment protocol. Acta Neurochir (Wien) 147:721–726CrossRef
39.
Zurück zum Zitat Gaspar K, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three RTOG brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751PubMedCrossRef Gaspar K, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three RTOG brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751PubMedCrossRef
40.
Zurück zum Zitat Bartsch R, Fromm S, Rudas M et al (2006) Intensified local treatment and sytemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer – A retrospective analysis. Radiother Oncol 80:313–317PubMedCrossRef Bartsch R, Fromm S, Rudas M et al (2006) Intensified local treatment and sytemic therapy significantly increase survival in patients with brain metastases from advanced breast cancer – A retrospective analysis. Radiother Oncol 80:313–317PubMedCrossRef
41.
Zurück zum Zitat Tham YL, Sexton K, Kramer R et al (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704PubMedCrossRef Tham YL, Sexton K, Kramer R et al (2006) Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 107:696–704PubMedCrossRef
42.
Zurück zum Zitat Rosner D, Nemoto T, Lane WW (1986) Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 58:832–839PubMedCrossRef Rosner D, Nemoto T, Lane WW (1986) Chemotherapy induces regression of brain metastases in breast carcinoma. Cancer 58:832–839PubMedCrossRef
43.
Zurück zum Zitat Boogerd W, Dalesio O, Bais EM et al (1992) Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 69:972–980PubMedCrossRef Boogerd W, Dalesio O, Bais EM et al (1992) Response of brain metastases from breast cancer to systemic chemotherapy. Cancer 69:972–980PubMedCrossRef
44.
Zurück zum Zitat Lin NU, Bellon BR, Winer EP (2004) CNS Metastases in breast cancer. J Clin Oncol 22:3608–3617PubMedCrossRef Lin NU, Bellon BR, Winer EP (2004) CNS Metastases in breast cancer. J Clin Oncol 22:3608–3617PubMedCrossRef
45.
Zurück zum Zitat Stemmler HJ, Schmitt M, Willems A et al (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impaired blood-brain-barrier. Anticancer Drugs 18:23–28PubMedCrossRef Stemmler HJ, Schmitt M, Willems A et al (2007) Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impaired blood-brain-barrier. Anticancer Drugs 18:23–28PubMedCrossRef
46.
47.
Zurück zum Zitat Patchell RA, Tibbs PA, Walsh JW et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500PubMedCrossRef Patchell RA, Tibbs PA, Walsh JW et al (1990) A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322:494–500PubMedCrossRef
48.
Zurück zum Zitat Noordijk EM, Vecht CJ, Haaxma-Reiche H et al (1994) The choice of treatment of single brain metastasis should be based on extracranial tumor activity and stage. Int J Radiat Oncol Biol Phys 29:711–717PubMed Noordijk EM, Vecht CJ, Haaxma-Reiche H et al (1994) The choice of treatment of single brain metastasis should be based on extracranial tumor activity and stage. Int J Radiat Oncol Biol Phys 29:711–717PubMed
Metadaten
Titel
Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer
verfasst von
Rupert Bartsch
Andrea Rottenfusser
Catharina Wenzel
Karin Dieckmann
Ursula Pluschnig
Gabriela Altorjai
Margaretha Rudas
Robert M. Mader
Richard Poetter
Christoph C. Zielinski
Guenther G. Steger
Publikationsdatum
01.12.2007
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2007
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-007-9420-5

Weitere Artikel der Ausgabe 3/2007

Journal of Neuro-Oncology 3/2007 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

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