|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
© 2002 American Society for Clinical Oncology
Perioperative Chemotherapy in Patients With Node-Negative Postmenopausal Breast CancerLeiden University Medical Center, Leiden, the Netherlands To the Editor:In the November 1, 2001, issue of the Journal of Clinical Oncology, Colleoni et al1 describe the potential relevance of perioperative chemotherapy for patients with node-negative breast cancer whose tumors do not express steroid hormone receptors. The authors present the Kaplan-Meier plot of disease-free survival comparing perioperative chemotherapy with no adjuvant treatment for 99 postmenopausal patients with node-negative estrogen receptor (ER)–absent disease, demonstrating a significant beneficial effect (relative risk 0.25; P = .0007) of perioperative chemotherapy in this subset of patients. All patients were selected from the International Breast Cancer Study Group Trial V, which enrolled 1,275 eligible breast cancer patients with node-negative disease; patients were randomized between one cycle of perioperative cyclophosphamide, methotrexate, fluorouracil, and leucovorin (commenced within 36 hours after mastectomy) versus no adjuvant treatment.2 The European Organization for Research and Treatment of Cancer (EORTC) Breast Group conducted EORTC Trial 10854 to compare one course of fluorouracil, doxorubicin, and cyclophosphamide versus no perioperative chemotherapy in patients with early-stage breast cancer.3 From 1986 to 1991, 2,793 patients were randomized. In this trial, 196 node-negative postmenopausal ER-negative patients were enrolled. Information on tumor progesterone content was not collected in this study. In our subset of node-negative postmenopausal ER-negative patients, 10-year progression-free survival results are not significantly different between patients who received perioperative chemotherapy and patients who did not (hazard ratio 0.78; P = .30). Patient specifications are listed in Table 1.
Although adjuvant chemotherapy in ER-negative breast cancer patients, regardless of menopausal status and nodal status, has been shown to improve disease outcome,4 the role of early timing of administration remains very much in doubt. Subgroup analyses in small subsets of patients will not yield a clear answer to this problem. In addition, neoadjuvant chemotherapy trials5,6 have not shown a benefit of early administration of chemotherapy with regard to progression-free or overall survival. REFERENCES
1.
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: 4141-4149, 2001 2. The Ludwig Breast Cancer Study Group: Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med 320: 491-496, 1989[Abstract] 3. 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: 2184-2193, 2001 4. Early Breast Cancer Trialists’ Collaborative Group: Polychemotherapy for early breast cancer: An overview of the randomised trials. Lancet 352: 930-942, 1998[CrossRef][Medline]
5.
van der Hage JA, van De Velde CJ, Julien JP, et al: Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Research and Treatment of Cancer Trial 10902. J Clin Oncol 19: 4224-4237, 2001 6. Wolmark N, Wang J, Mamounas E, et al: Preoperative chemotherapy in patients with operable breast cancer: Nine-year results from national surgical adjuvant breast and bowel project B-18. J Natl Cancer Inst Monogr 30: 96-102, 2001
Response
European Institute of Oncology, Milan, Italy In 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. REFERENCES 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: 2184-2193, 2001 2. 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: 4141-4149, 2001
3.
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: 584-590, 2000
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
