Study supports tailoring adjuvant therapy for early-stage breast cancer

Premenopausal women with lymph node-negative breast cancer should receive adjuvant therapy tailored according to the estrogen receptor status of the primary tumor, concludes a study by the International Breast Cancer Study Group (IBCSG) reported in the December 17 issue of the Journal of the National Cancer Institute.

Patients with estrogen receptor (ER)-negative (i.e., endocrine nonresponsive) breast cancer should receive adjuvant chemotherapy, according to the study, whereas for patients with ER-positive (i.e., endocrine responsive) tumors, the use of endocrine therapy alone or in combination with adjuvant chemotherapy requires further study.

Some studies have suggested that cytotoxic chemotherapy benefits premenopausal women with breast cancer because it causes premature menopause. The new study addresses whether adjuvant ovarian function suppression can be used as a replacement for or as a supplement to cytotoxic adjuvant chemotherapy for premenopausal women with early-stage breast cancer.

These findings support the idea that ovarian suppression “is a viable treatment alternative for at least some premenopausal women with breast cancer,” comment Joseph L. Pater, M.D., and Wendy R. Parulekar, M.D., of the National Cancer Institute of Canada Clinical Trials Group at Queen’s University in Kingston, Ontario, in an accompanying editorial.

In the study, Monica Castiglione-Gertsch, M.D., and her colleagues from the IBCSG, compared outcomes of 1,063 pre- and perimenopausal women who were previously treated for lymph-node negative (early-stage) breast cancer and randomly assigned to receive adjuvant chemotherapy, adjuvant therapy with the ovarian function suppression drug goserelin, or adjuvant chemotherapy followed by goserelin. The women were tested to determine the estrogen receptor status of their tumors.

After a median follow-up of 7 years, there was no difference in disease-free survival or overall survival among patients in the three treatment groups. However, a subgroup analysis revealed that patients with ER-negative tumors who received chemotherapy alone or followed by goserelin had better disease-free survival than patients who received goserelin alone. By contrast, among patients with ER-positive tumors, results were similar after chemotherapy alone or goserelin alone. Sequential use of chemotherapy followed by goserelin resulted in a statistically nonsignificant benefit that was limited to younger women.

The authors caution that their findings “should not alter current patient care, but rather emphasize the relevance of current studies of chemotherapy and endocrine agents.” The editorialists agree, recommending that future studies examine the selective use of ovarian suppression in women who are not rendered menopausal by chemotherapy.

Contact: Monica Castiglione-Gertsch, M.D., International Breast Cancer Study Group, 41-31-389-9191; fax: 41-31-389-9200, monica.castiglione@siak.ch.

To interview coauthor Richard Gelber, contact Janet Haley-Dubow, Dana-Farber Cancer Institute, 617-632-5665, janet_haley@dfci.harvard.edu.

Editorial: Nancy Dorrance, Queen’s University, 613-533-2869, dorrance@post.queensu.ca.
International Breast Cancer Study Group. 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.

Editorial: Pater JL, Parulekar WR. Ovarian ablation as adjuvant therapy for premenopausal women with breast cancer–another step forward. J Natl Cancer Inst 2003;95:1811–2.

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