Abstract
This is preliminary study assessing the efficacy and safety of concurrent use of radiation therapy (RT) and T-DM1 for the treatment of brain metastases (BM) in patients with HER2-positive metastatic breast cancer (BC). We retrospectively studied 12 patients treated for BM at the Institut Curie in 2014–2015 with T-DM1 and concurrent (4) or sequential (8) radiosurgery with or without whole brain irradiation. The following variables were studied: local control, clinical and radiological response as well as early and late side effects. The mean age of the population was 38 years at the time of diagnosis of BC and 46 years at of BM. All patients were with good PS. The response rate of the concurrent treatment group was 75 % with 1 complete response, 1 partial response, one stable disease and 1 progression. Comparatively, the response rate in the sequential group was as follows: two complete responses, two partial responses, six cases of stable disease and two cases of local progression. No patient experienced interruption of irradiation because of side effects. About 50 % of patients were asymptomatic after treatment. Radiation necrosis was observed in 50 % of patients in the concurrent group and 28.6 % of patients in the sequential group with a similar rate of oedema in the two groups. We found that the combination of T-DM1 and radiosurgery was feasible but can increase the incidence of radiation necrosis. Larger prospective studies with longer follow-up are needed to more clearly evaluate this association.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Rossi S, Baili P, Capocaccia R, Caldora M, Carrani E, Minicozzi P et al (2015) The EUROCARE-5 study on cancer survival in Europe 1999–2007: database, quality checks and statistical analysis methods. Eur J Cancer Oxf Engl. doi:10.1016/j.ejca.2015.08.001
Yardley DA, Kaufman PA, Huang W, Krekow L, Savin M, Lawler WE et al (2015) Quantitative measurement of HER2 expression in breast cancers: comparison with “real-world” routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival. Breast Cancer Res BCR 17:41
Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by her2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182
Biswas G, Bhagwat R, Khurana R, Menon H, Prasad N, Parikh PM (2006) Brain metastasis–evidence based management. J Cancer Res Ther 2(1):5–13
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672
Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol Off J Am Soc Clin Oncol 23(19):4265–4274
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792
Junttila TT, Li G, Parsons K, Phillips GL, Sliwkowski MX (2011) Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res Treat 128(2):347–356
Krop IE, Lin NU, Blackwell K, Guardino E, Huober J, Lu M et al (2015) Trastuzumab emtansine (T-DM1) vs. lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol Off J Eur Soc Med Oncol ESMO 26(1):113–119
Chargari C, Idrissi HR, Pierga J-Y, Bollet MA, Diéras V, Campana F et al (2011) Preliminary results of whole brain radiotherapy with concurrent trastuzumab for treatment of brain metastases in breast cancer patients. Int J Radiat Oncol Biol Phys 81(3):631–636
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367(19):1783–1791
Shoji Yomo MH (2013) Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer. J Neurooncol 112(2):199–207
Borges GS, Rovere RK, Dias SMK, Chong FH, Morais M dos S (2015) Safety and efficacy of the combination of T-DM1 with radiotherapy of the central nervous system in a patient with HER2-positive metastatic breast cancer: case study and review of the literature. ecancermedicalscience [Internet] [cited 2016 Jan 27]; 9. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631578/
Bartsch R, Rottenfusser A, Wenzel C, Dieckmann K, Pluschnig U, Altorjai G et al (2007) Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer. J Neurooncol 85(3):311–317
Géraud A, Xu HP, Beuzeboc P, Kirova YM (2016) Preliminary results of the concurrent use of radiotherapy for bone metastases and trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. Cancer Radiother 20(4):312–313
Le Rhun E, Dhermain F, Vogin G, Reyns N, Metellus P (2016) Radionecrosis after stereotactic radiotherapy for brain metastases. Expert Rev Neurother 16(8):903–914
Carlson JA, Nooruddin Z, Rusthoven C, Elias A, Borges VF, Diamond JR et al (2014) Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema. Neuro-Oncol 16(7):1006–1009
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflicts of interest.
Rights and permissions
About this article
Cite this article
Geraud, A., Xu, H.P., Beuzeboc, P. et al. Preliminary experience of the concurrent use of radiosurgery and T-DM1 for brain metastases in HER2-positive metastatic breast cancer. J Neurooncol 131, 69–72 (2017). https://doi.org/10.1007/s11060-016-2265-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11060-016-2265-z