her2+ER- can change to her2+ER+, allowing other treatment options

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free open access article
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Reverting estrogen-receptor-negative phenotype in HER-2-overexpressing advanced breast cancer patients exposed to trastuzumab plus chemotherapy
Elisabetta Munzone1 , Giuseppe Curigliano1 , Andrea Rocca1 , Giuseppina Bonizzi2 , Giuseppe Renne3 , Aron Goldhirsch1 and Franco Nolè1
1Department of Medicine, Division of Medical Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
2Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy
3Division of Pathology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy

Breast Cancer Research 2006, 8:R4 doi:10.1186/bcr1366




© 2005 Munzone et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction

The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer.

Methods

Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy.

Results

Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression.



Therapeutic targets enabling the appearance of an endocrine responsive disease may increase treatment options for patients with breast cancer. Furthermore, these clinical data suggest that an ER-negative phenotype is a multi-step process with a reversible repression modality, and that some ER-negative tumors may either revert to an ER-positive phenotype, allowing an endocrine treatment to be effective.