Annals of Oncology Advance Access originally published online on September 4, 2007
Annals of Oncology 2007 18(12):1963-1968; doi:10.1093/annonc/mdm417
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© 2007 European Society for Medical Oncology
breast cancer |
Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin® are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study
1 Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Torino, Torino, Italy
2 Divisione Universitaria di Oncologia Medica ed Ematologia, Istituto per la Ricerca e la Cura del Cancro, Candiolo Torino, Italy
3 Divisione di Anatomia Patologica e Medicina di Laboratorio, Istituto Europeo di Oncologia e Università degli Studi, Milano, Italy
4 Budapest Faculty of Medicine, Semmelweis University, Hungary
5 Centro Onco-Ematologico Subalpino, Ospedale San Giovanni Battista, Molinette, Torino, Italy
6 Breast Unit, Istituti Ospitalieri, Cremona, Italy
7 Istituto Nazionale Tumori, Fondazione Senatore Pascale, Napoli, Italy
8 Dipartimento di Patologia, Ospedale Regionale, Treviso, Italy
9 Royal Surrey County Hospital, Guildford, Surrey, UK
10 Istituto Nazionale per la Ricerca sul Cancro (IST), Genova, Italy
11 Divisione di Oncologia Medica, Istituto Europeo di Oncologia, Milano, Italy
* Correspondence to: Prof. A. Sapino, Department of Biomedical Sciences and Human Oncology, Via Santena 7, Turin, Italy. Tel: +39 011-6334127; Fax: +39 011-6635267; E-mail: anna.sapino{at}unito.it
Background: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab.
Patients and methods: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes.
Results: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%–81%] and 47% (95% CI 36%–58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952–7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303–0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368–0.870) by multivariate analysis.
Conclusion: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.
Key words: biotin-labeled trastuzumab, breast neoplasms, HER2
These authors contributed equally to this work. Received for publication June 14, 2007. Revision received July 16, 2007. Accepted for publication July 18, 2007.