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ADJUVANT SYSTEMIC THERAPY FOR NODE-NEGATIVE BREAST CANCER.

Nearly 15 years ago, clinical trials first demonstrated the benefit of adjuvant chemotherapy in breast cancer patients with positive axillary nodes but without clinically evident distant metastases. The next logical step was to perform similar trials in patients with negative nodes. This issue of the New England Journal of Medicine reports four such studies, which yielded remarkably similar results. Subjects in all studies were node-negative, had had standard surgery for the primary tumor prior to adjuvant therapy, and were followed for an average of three to four years. The National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized 679 patients with estrogen receptor (ER)- negative breast cancer to receive 12 courses of chemotherapy (methotrexate, fluorouracil, and leucovorin) or no additional treatment. Chemotherapy increased disease-free survival rates from 71 to 80 percent. In a second NSABP study, 2644 patients with ER-positive tumors received either tamoxifen or placebo. Disease-free survival was better with tamoxifen than with placebo (83 versus 77 percent).

Mansour and colleagues randomized 536 women with ER- negative cancer or large (greater than 3 cm) ER-positive tumors to receive six cycles of chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone) or no treatment. Disease-free survival again favored the treatment group (84 versus 69 percent). This was the most aggressive of the four treatment regimens and toxicity was accordingly the highest (33 percent incidence of leukopenia and one treatment-associated death).

And finally, an international group based in Switzerland randomized 1275 patients to receive either a single cycle of chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and leucovorin) initiated 36 hours after surgery or no treatment. A small difference in disease-free survival favored chemotherapy (77 versus 73 percent).

All the differences cited above were statistically significant. The results taken collectively thus make a strong case for adjuvant systemic therapy in node-negative breast cancer. One should note, however, that overall survival (as opposed to disease-free survival) was not improved in any treatment group, possibly because of the relatively short follow-up periods. Moreover, historical data indicate that roughly 70 percent of node-negative patients survive for long periods without adjuvant therapy. Many patients destined to do well must therefore be treated in order to benefit relatively few. Researchers are attempting to devise more reliable methods of identifying subgroups of patients most likely to benefit from adjuvant therapy.

— ASB

Published in Journal Watch General Medicine March 3, 1989

Citation(s):

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 1989 Feb 23 320 491-496.

• Medline abstract (Free)

Mansour EG et al. Efficacy of adjuvant chemotherapy in high-risk node- negative breast cancer: an intergroup study. N Engl J Med 1989 Feb 23 320 485-490.

• Medline abstract (Free)

Fisher B et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 1989 Feb 23 320 479-484.

• Medline abstract (Free)

Fisher B et al. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor- negative tumors. N Engl J Med 1989 Feb 23 320 473-478.

• Medline abstract (Free)