Journal of the National Cancer Institute Advance Access originally published online on September 11, 2007
JNCI Journal of the National Cancer Institute 2007 99(18):1416; doi:10.1093/jnci/djm109
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Re: Polychemotherapy for Early Breast Cancer: Results From the International Adjuvant Breast Cancer Chemotherapy Randomized Trial
Affiliations of authors: Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy
Correspondence to: Gianluigi Ferretti, MD, PhD, Division of Medical Oncology A, Regina Elena Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy (e-mail: gia.fer{at}flashnet.it).
According to the Adjuvant Breast Cancer Trials Collaborative Group (ABCTCG) trial (1), improvements (non–statistically significant in relapse-free survival but statistically significant in overall survival) with chemotherapy combined with tamoxifen were seen especially among women younger than age 50 years and in particular premenopausal women who did not receive ovarian ablation or suppression (usually delivered after chemotherapy by radiation or surgery). However, the finding that patients younger than 40 years benefited less from chemotherapy than those aged 40–49 years (1) is consistent with the possibility that, in premenopausal women, polychemotherapy can mediate a part of its effects through chemical castration. Consequently, women with hormone receptor–positive breast cancer who did not experience amenorrhea after chemotherapy could be the ones who benefit most from the addition of a luteinizing hormone–releasing hormone (LHRH) agonist. In addition, according to the LHRH agonists in Early Breast Cancer Overview group’s study (2), among women aged 40 years or younger; the addition of an LHRH agonist to chemotherapy with or without tamoxifen statistically significantly reduced rates for recurrence by 25.2% (P = .01), death after recurrence by 28.3% (P = .01), and all deaths by 27.4% (P = .01). Furthermore, a subgroup analysis of the International Breast Cancer Study Group Trial VIII (3) found that younger women (<40 years), who are least likely to develop chemotherapy-induced amenorrhea, experienced a statistically significant benefit with combined treatment (cyclophosphamide–methotrexate–fluorouracil followed by goserelin) versus cyclophosphamide–methotrexate–fluorouracil alone. Moreover, in the Eastern Cooperative Oncology Group phase III intergroup trial (4), hypothesis-generating subgroup analyses suggested that women younger than 40 years and those with premenopausal estradiol levels or menses after chemotherapy benefited the most from the addition of goserelin.
According to Cuzick et al. (2), LHRH agonists compared with no systemic treatment did not have a statistically significant effect on recurrence, death after recurrence, or death from any cause in hormone receptor–positive cancers. But the effect of goserelin has been reported to be greatest in patients with estrogen receptor (ER)–positive tumors who had not received chemotherapy (5). Another ABCTCG trial (6) suggested that younger women (aged <40 years) who did not receive chemotherapy could experience a clinical benefit from ovarian ablation or suppression that was slightly greater if women with ER-negative breast cancer were excluded. According to the Zoladex in Premenopausal Patients Trial (7), the effect of goserelin (Zoladex) was greatest in patients with ER-positive tumors who had not received chemotherapy.
In the LHRH agonists in Early Breast Cancer Overview group's study, no trial had assessed an LHRH agonist versus chemotherapy with tamoxifen in both arms (2). Thus, in patients with hormone receptor–positive breast cancer, the question immediately arises as to what additional benefit is achievable by an LHRH agonist after chemotherapy in women without amenorrhea with respect to the use of an LHRH agonist upfront as the only systemic adjuvant treatment, in younger women who did not receive adjuvant chemotherapy. Further investigations are needed to address this specific issue.
REFERENCES
(1) The Adjuvant Breast Cancer Trials Collaborative Group. Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized trial. J Natl Cancer Inst (2007) 99:506–15.
(2) Cuzick J, Ambroisine L, Davidson N, Jakesz R, Kaufmann M, Regan M, Sainsbury R, LHRH-agonists in Early Breast Cancer Overview group;. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet (2007) 369:1711–23.[CrossRef][Web of Science][Medline]
(3) Castiglione-Gertsch M, O'Neill A, Price KN, Goldhirsch A, Coates AS, Colleoni M, et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst (2003) 95:1833–46.
(4) Davidson NE, O'Neill AM, Vukov AM, Osborne CK, Martino S, White DR, et al. Chemoendocrine therapy for premenopausal women with axillary lymph node-positive, steroid hormone receptor-positive breast cancer: results from INT 0101 (E5188). J Clin Oncol (2005) 23:5973–82.
(5) Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, et al. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study. J Clin Oncol (2002) 20:4628–35.
(6) The Adjuvant Breast Cancer Trials Collaborative Group. Ovarian ablation or suppression in premenopausal early breast cancer: results from the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial. In: J Natl Cancer Inst (2007) 99:516–25.
(7) Baum M, Hackshaw A, Houghton J, Rutqvist LE, Fornander T, Nordenskjold B, et al. ZIPP International Collaborators’ Group. Adjuvant goserelin in pre-menopausal patients with early breast cancer: results from the ZIPP study. Eur J Cancer (2006) 42:895–904.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2007 99: 506-515.
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