previously set out to be. There are Durable complete responses of Stage IV patients and this article set out to examine them. Shows how important it is to include herceptin in first line treatment of Stage IV and how important it is to continue it-- feel free to show this to governments/insurance companies who don't want to pay for herceptin!
From Annals of Oncology Ann Oncol. 2012 Jul 5. [Epub ahead of print]
Durable complete response following chemotherapy and trastuzumab for metastatic HER2-positive breast cancer
G. Gullo1,*, M. Zuradelli2, F. Sclafani1, A. Santoro2 and J. Crown1
+ Author Affiliations
1Department of Oncology, St Vincent's University Hospital, Dublin, Ireland;
2Oncology and Haematology Unit, Humanitas Cancer Center, Rozzano, Italy
↵*(E-mail:
g.gullo@svuh.ie)
Individual cases of prolonged complete response (CR) of HER2-positive metastatic breast cancer (MBC) have been reported following treatment with trastuzumab/chemotherapy, but the frequency of durable remission is unknown [1, 2].
We carried out a retrospective study of long-term outcome of all patients with HER2-positive MBC treated in our institutions with chemotherapy and trastuzumab before March 2007. All patients had histology-proven, HER2-positive (3+ on immunohistochemistry and/or HER2/neu gene amplification on FISH) breast cancer. None had received adjuvant trastuzumab.
Eighty-four patients were treated from May 2000 to March 2007 (Table 1). Thirteen (15%) achieved CR as defined according to RECIST 1.0 criteria [3]. As part of different institutional practices, patients in Dublin continued on trastuzumab until progression or at least for five years. In Milan trastuzumab was generally stopped in CR patients within two years of achieving remission. As of March 17, 2012, (median follow up 7 years, range 2.5–11.8 years), six of these patients remain alive and continuously cancer free at 142, 139, 122, 101, 84, and 84 months. Two additional patients are alive and continuously free of metastatic cancer at 107 and 105 months, having received curative locoregional therapy for new primary breast cancers. Five patients who achieved CR have developed relapsed MBC, at 44, 37, 35, 30, and 15 months, two while receiving maintenance trastuzumab (at 44 and 37 months, respectively). Three others had discontinued trastuzumab (21, 8, and 4 months after cessation).
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Table 1.
Characteristics of patients
All of the eight DCR patients received trastuzumab together with their first chemotherapy for metastatic disease. Five (63%) DCR patients had estrogen receptor (ER) negative disease, and five had metastases limited to liver. All but one received a taxane-containing regimen with trastuzumab (docetaxel and carboplatin-4 and single agent taxane-3).
The median duration of trastuzumab for CR patients in the two institutions was 67 months (range: 49 to 107+) in Dublin and 14 months (range 5–26) in Milan. Interestingly, although the frequency of CR was very similar in the two institutions (Milan 16% and Dublin 15%), the proportion of patients with DCR was higher in Dublin than Milan (11% versus 6%, respectively), prompting speculation that the duration of trastuzumab therapy might be important.
This is the first reported series of long-term follow-up of patients with HER2-positive MBC who achieved CR following chemotherapy and trastuzumab. Our data suggest that a meaningful minority of patients achieve very prolonged complete remissions. Although the small numbers and the retrospective nature of the study preclude definitive statistics, the data also suggest that the impact of trastuzumab might be greater in patients with ER-negative disease (14% DCR—an observation consistent with trials conducted in earlier stage disease [4, 5]) and possibly in those with metastases confined to the liver. Furthermore, the complete absence of DCR among patients who received trastuzumab with their second or subsequent chemotherapy for metastatic disease suggests that this agent should be a component of initial treatment. For patients with ER-negative disease who received trastuzumab with first line chemotherapy, the DCR rate is 16%.
At present we are conducting a comprehensive molecular and cytogenetic study of these patients' tumor samples to identify a subset of patients with HER2-positive MBC who are more likely to achieve DCR following chemotherapy plus trastuzumab.
We hypothesize that overtly HER2-positive MBC may be a potentially curable disease.
The authors declare no conflicts of interest.
© The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email:
journals.permissions@oup.com.
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references
↵ Beda M, Basso U, Ghiotto C, et al. When should trastuzumab be stopped after achieving complete response in HER2-positive metastatic breast cancer patients? Tumori 2007;93:491-492.
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↵ Maciá Escalante S, Rodr*guez Lescure Á, Pons Sanz V, et al. A patient with breast cancer with hepatic metastases and a complete response to herceptin as monotherapy. Clin Transl Oncol 2006;8:761-763.
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↵ Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors: European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216.
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↵ Gianni L, Eiermann W, Semiglazov V, et al. 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 2010;375:377-384.
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↵ Baselga J, Bradbury I, Eidtmann H, et al. First results of the NeoALTTO Trial (BIG 01-06 / EGF 106903): 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 2011;70:24. abstr S3–3.
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MUST READ-- metastatic her2+ breast cancer not necessarily the death sentence it was
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