Chemotherapy Does Not Add to the Benefits of Tamoxifen in Node-Negative, ER-Positive Older Breast Cancer Patients

March 1, 2003

PITTSBURGH-Long-term follow-up data from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials of tamoxifen plus chemotherapy in node-negative, estrogen receptor (ER)-positive breast cancer patients suggest that chemotherapy does not add to the benefits of tamoxifen among women aged 60 or older. Bernard Fisher, MD, distinguished service professor at the University of Pittsburgh and past chairman and scientific director of the NSABP, reviewed the results of several trials, beginning with NSABP B-20. That trial established the value of combining cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) with tamoxifen in node-negative, estrogen receptor-positive women.

PITTSBURGH—Long-term follow-up data from National Surgical Adjuvant Breast and Bowel Project (NSABP) trials of tamoxifen plus chemotherapy in node-negative, estrogen receptor (ER)-positive breast cancer patients suggest that chemotherapy does not add to the benefits of tamoxifen among women aged 60 or older. Bernard Fisher, MD, distinguished service professor at the University of Pittsburgh and past chairman and scientific director of the NSABP, reviewed the results of several trials, beginning with NSABP B-20. That trial established the value of combining cyclophosphamide (Cytoxan, Neosar), methotrexate, and fluorouracil (CMF) with tamoxifen in node-negative, estrogen receptor-positive women.

A 5-year follow-up analysis found that breast cancer risk reductions were significantly greater among women treated with CMF plus tamoxifen (CMFT) than among those given tamoxifen alone-46% vs 26%. At that time, the researchers noted that these risk reductions were greater among women age 49 or younger than among those age 50 or older.

Dr. Fisher said that with the more prolonged follow-up time, and in view of issues recently raised about the administration of chemotherapy and tamoxifen, the group had updated their findings and had found them compelling. With a median follow-up of approximately 12 years, the influence of age on chemotherapy benefit has come into sharper focus.

Analyzed by Variables

Among women aged 49 or younger and among those age 50 to 59, CMFT was superior to tamoxifen alone for all study endpoints-disease-free survival, relapse-free survival, distant-disease-free survival, and overall survival. This was not true for women aged 60 or older. In this older group, CMF did not improve upon or negate the findings from tamoxifen alone.

When the investigators analyzed the data according to menopausal status, as reported to the NSABP data center, they found similar results. "Patients designated as premenopausal received a remarkably good benefit from CMF plus tamoxifen," Dr. Fisher said. CMFT offered no advantage over tamoxifen alone among those in the postmenopausal group.

When the treatment benefits were analyzed by age or menopausal status, neither variable affected the benefits of tamoxifen alone. But in the CMFT patients, those who were aged 49 or younger, aged 50 to 59, or premenopausal did much better than did those who were aged 60 or older or who were postmenopausal.

Reduced Treatment Failure

To answer "How much has really been accomplished in treating these patients?" the NSABP investigators reviewed the results of the B-14 and B-20 trials together. The B-14 trial, which was the first to examine the value of tamoxifen in node-negative, ER-positive tumors, now has a median follow-up of 15 years. When analyzed together, the trials showed CMFT resulted in a 56% reduction in treatment failure compared to the placebo group in B-14 and a 25% actual difference in benefit among patients age 49 or younger.

Among patients age 50 to 59, the risk reduction was 48% (20% actual difference in benefit). But among patients age 60 or older, the risk reduction was 26% (13% actual difference in benefit, similar to that obtained with tamoxifen).

"Only in our experience with the prevention trial have we seen such a remarkable effect," Dr. Fisher said.

"Our findings suggest that in average clinical practice, age is likely to be a satisfactory discriminant for deciding upon the use of CMFT."