Postmenopausal women with lymph node-negative breast cancers—or breast cancers that have not spread to the lymph nodes—accounted for nearly half of all women who underwent breast cancer surgery between 1992 and 1996 in the United States. While adjuvant therapy with tamoxifen has been shown to reduce the risk of breast cancer recurrence among women with ER-positive breast cancers, there is little information about whether adding chemotherapy to tamoxifen would be of benefit. Past studies have suggested that combining chemotherapy with tamoxifen improves survival of postmenopausal women with lymph node-positive breast cancer.
To examine the benefit of such combined therapy on postmenopausal women with lymph node-negative breast cancer, Monica Castiglione-Gertsch, M.D., of the International Breast Cancer Study Group, and her colleagues from Dana-Farber Cancer Institute and several other institutions, randomly assigned 1,669 postmenopausal women to receive either chemotherapy followed by tamoxifen or tamoxifen alone for 5 years. Because women with ER-positive breast cancers (breast cancers that express the estrogen receptor and are dependent on estrogen) are more likely to respond to tamoxifen, the women were divided into two groups according to their estrogen receptor status.
Among women with lymph node-negative, ER-negative breast cancer, chemotherapy before tamoxifen increased their 5-year disease-free survival rate from 69% to 84% and their 5-year overall survival from 81% to 89% compared with tamoxifen alone. However, women with lymph node-negative, ER-positive breast cancer received no survival benefit from the addition of chemotherapy.
Despite study limitations (such as a short course of chemotherapy) that may have benefited patients with ER-positive tumors, the authors maintain that "postmenopausal women with lymph node-negative breast cancer should be treated with a much more individualized adjuvant program than is currently prescribed."
They say that results from this and other studies indicate that postmenopausal patients with lymph node-negative, ER-negative disease benefit substantially from adjuvant chemotherapy. In contrast, the benefit of adjuvant chemotherapy for postmenopausal patients with lymph node-negative, ER-positive disease is less clear, although these patients should continue to receive tamoxifen alone, the authors say.
In an accompanying editorial, Antonio C Wolff, M.D., and Martin D. Abeloff, M.D., of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, say that the true benefit from any therapy must take into account the impact of therapy on quality of life, especially among older patients. They point out that although the study showed a modest decrease in quality of life during chemotherapy, these findings do not justify withholding therapy.
They add that these findings reinforce the cautionary tone that exists in recent clinical practice guidelines and is a "wake-up call" to the research community to increase accrual of older women to clinical trials and focus on the development of new chemotherapy and molecularly targeted agents with more selectivity and reduced toxicity.
Contact: Monica Castiglione-Gertsch, M.D., International Breast Cancer Study Group, +41 31 389 91 91; fax: +41 31 389 92 00, mcastiglione@sakk.ch.
Coauthors from Dana-Farber Cancer Institute may be contacted through Bill Schaller, (617) 632-5357; fax: (617) 632-4069, william_schaller@dfci.harvard.edu.
Editorial: Vanessa Wasta, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, (410) 955-1287.
Castiglione-Gertsch M, Price K, Goldhirsch A, Coates A, Colleoni M, Nasi M, et al. Endocrine responsiveness and tailoring adjuvant therapy for postmenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 2002;94:1054–65.
Wolff A, Abeloff M. Adjuvant chemotherapy for postmenopausal lymph node-negative breast cancer: it ain't necessarily so. J Natl Cancer Inst 2002;94:1041–3.
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JNCI Journal of the National Cancer Institute