ASCO--Women with estrogen receptor (ER)-positive breast cancer who have no evidence of lymph node involvement should be added to the list of breast cancer patients who can benefit from adjuvant chemotherapy, Bernard Fisher, MD, said at the plenary session of the 33rd Annual ASCO Meeting.
In his presentation of the results of NSABP protocol B-20, Dr. Fisher said that no subgroup of patients could be identified who failed to derive a benefit from the addition of chemotherapy to tamoxifen(Drug information on tamoxifen) (Nolvadex).
The findings support a "unified approach to systemic adjuvant therapy," said Dr. Fisher, scientific director of the NSABP. "The findings permit the conclusion that all patients who meet NSABP protocol criteria, regardless of age, nodal status, or ER status, are candidates for chemotherapy."
Since the trial excluded women with nonpalpable, mammographically detected lesions or very small tumors, the appropriateness of chemotherapy in these subgroups is still unclear.
The 2,363 women who participated in the trial, all with ER-positive, node-negative disease, were randomly assigned to one of three regimens: tamoxifen alone; tamoxifen plus six cycles of sequential methotrexate(Drug information on methotrexate) and fluorouracil(Drug information on fluorouracil) followed by leucovorin rescue; or tamoxifen plus cyclophosphamide(Drug information on cyclophosphamide), methotrexate, and fluorouracil.
Women treated with either combination regimen had a significantly higher five-year disease-free survival rate than those given tamoxifen alone (90% vs 85%; P = .002). A difference in overall survival between women who did and did not receive chemotherapy also has begun to emerge, with five-year survival rates of 97% and 94%, respectively (P = .02).
Moreover, both chemotherapy regimens decreased the risk of locoregional, distant, and ipsilateral breast tumor recurrence. "For each treatment for each comparison . . . the risk was reduced between 25% and 50%," Dr. Fisher said. In women aged 49 or younger, chemotherapy decreased the risk of treatment failure, distant disease, and death by about 50%, he said. Although the magnitude of risk reduction was somewhat smaller in women over 50, they, too, derived benefit from the addition of chemotherapy.
Node Dissection Questioned
One controversial implication of NSABP-B-20 relates to the necessity of performing lymph node dissection. "The current findings eliminate the need for knowing axillary status in order to make decisions regarding the use of systemic therapy," Dr. Fisher said.
Another reason for dissecting the nodes--helping to determine prognosis--may eventually be rendered obsolete by new predictors, he said at a press briefing. Likewise, the use of node dissection to achieve better local control may be supplanted by other therapies, such as tamoxifen and chemotherapy. Such findings, Dr. Fisher said, are rapidly leading to "more rational decision-making" about the need for axillary node dissection.
Should All Women Receive Chemo?
In his discussion of the trial at the plenary session, Dr. Trevor Powles, Royal Marsden Hospital, London, agreed with Dr. Fisher that current prognostic markers fail to differentiate between women who will and will not benefit from chemotherapy, and concurred that most women with breast cancer probably should receive chemotherapy. However, he warned that the indiscriminate use of chemotherapy has the potential for "substantial overtreatment with toxicity."
The trial, he said, probably represents the "end of the road" for large, indiscriminate chemotherapy trials. Instead, he argued, researchers need to incorporate predictive diagnostic tests into chemotherapy trials, in order to select and optimize adjuvant therapy.