Perioperative Chemotherapy in Patients With Node-Negative Postmenopausal Breast Cancer
Authors: Jos A. van der Hage, Cornelis J.H. van de Velde, Marco Colleoni, Aron Goldhirsch, Alan S. Coates, Richard D. Gelber, Shari Gelber, Monica Castiglione-Gertsch
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.8.2210 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11956284 Perioperative Chemotherapy in Patients With Node-Negative Postmenopausal Breast Cancer Jos A. van der HagexJos A. van der HageSearch for articles by this author , Cornelis J.H. van de VeldexCornelis J.H. van de VeldeSearch for articles by this author Marco ColleonixMarco ColleoniSearch for articles by this author , Aron GoldhirschxAron GoldhirschSearch for articles by this author , Alan S. CoatesxAlan S. CoatesSearch for articles by this author , Richard D. GelberxRichard D. GelberSearch for articles by this author , Shari GelberxShari GelberSearch for articles by this author , Monica Castiglione-GertschxMonica Castiglione-GertschSearch for articles by this author , Show More Leiden University Medical Center, Leiden, the NetherlandsEuropean Institute of Oncology, Milan, ItalyAustralian Cancer Society, University of Sidney, Sidney, AustraliaInternational Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Boston, MAInternational Breast Cancer Study Group Coordination Center, Bern, Switzerland https://doi.org/10.1200/JCO.2002.20.8.2210 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15042002In Reply:We thank Drs van der Hage and van de Velde for providing the data on their short-duration, perioperative cytotoxic adjuvant treatment for a so-called postmenopausal population with estrogen receptor (ER)–negative, node-negative breast cancer.1 This gives us the opportunity to reemphasize that the key feature for our observation2 is the precise selection of the population in which we performed the retrospective analysis. Our patients were all postmenopausal based on absence of ovarian function, whereas the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854 “postmenopausal” cohort included all women older than 50 years, some of whom are likely to have residual ovarian function. Our analysis focused on patients with tumors expressing no steroid hormone receptors (ER and progesterone receptor [PgR]–absent group), whereas the EORTC analysis included all patients with ER-negative tumors, some of which presumably expressed receptor levels between 1 and 9 fmol/mg of cytosol protein. In fact, we observed a slightly larger effect of the one course of chemotherapy in the subpopulation with both ER and PgR absent (77 patients, hazard ratio [HR] 0.18; P = .0009) compared with the effect observed when the subpopulation was selected only on the basis of the absence of ER (99 patients, HR 0.25; P = .0007). We would therefore interpret the results of the EORTC Trial 108541 as follows: the subpopulation of 196 patients, older than age 50 years (of whom many may have been premenopausal or perimenopausal), and with “ER-negative” disease (ER either absent or measured to be between 1 and 9 fmol/mg of cytosol protein), showed a similar outcome to ours (HR 0.78), although the degree of statistical uncertainty is much larger because of the lesser magnitude effect of therapy. It is entirely consistent with the data that their observation would have been much more similar to ours if they had more rigorously defined the subgroup of interest as indicated in our discussion.2 The more definitive attempt to reproduce our retrospective observation would have been to identify a subpopulation with no residual ovarian function and to limit participation to those whose tumors on immunohistochemical evaluation showed no expression of ER and PgR, then to assess responsiveness to brief early cytotoxic treatment in this more comparable group. Similarly, the neoadjuvant chemotherapy trials presented as evidence against the role of early initiation have never been evaluated specifically for the steroid hormone receptor–absent cohort.Finally, we agree that a prospective evaluation of early timing of adjuvant cytotoxics in a population for which timing is predicted to be important (eg, patients with tumors not expressing any steroid hormone receptor) would be valuable. We foresee, however, some reluctance in proposing a delayed treatment for these patients due to other observations made by our group suggesting the importance of timing and duration of chemotherapy.3 We recommend that other groups with information on early initiation of chemotherapy evaluate their treatment results within the “evidence-based” subset of breast cancer patients with ER- and/or PgR-absent tumors.1. van der Hage JA, van de Velde CJ, Julien JP, et al: Improved survival after one course of perioperative chemotherapy in early breast cancer patients: Long-term results from the European Organization for Research and Treatment of Cancer (EORTC) Trial 10854. Eur J Cancer 37:: 2184,2001-2193, Crossref, Medline, Google Scholar2. Colleoni M, Gelber S, Coates AS, et al: Influence of endocrine-related factors on response to perioperative chemotherapy for patients with node-negative breast cancer. J Clin Oncol 19:: 4141,2001-4149, Link, Google Scholar3. Colleoni M, Bonetti M, Coates AS, et al: Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. J Clin Oncol 18:: 584,2000-590, Link, Google Scholar