Chemo Benefits ER+, Node-Negative Women

ASCO--Women with estrogen receptor (ER)-positive breast cancer who haveno evidence of lymph node involvement should be added to the list of breastcancer patients who can benefit from adjuvant chemotherapy, Bernard Fisher,MD, said at the plenary session of the 33rd Annual ASCOMeeting.

In his presentation of the results of NSABP protocol B-20, Dr. Fishersaid that no subgroup of patients could be identified who failed to derivea benefit from the addition of chemotherapy to tamoxifen (Nolvadex).

The findings support a "unified approach to systemic adjuvant therapy,"said Dr. Fisher, scientific director of the NSABP. "The findings permitthe conclusion that all patients who meet NSABP protocol criteria, regardlessof age, nodal status, or ER status, are candidates for chemotherapy."

Since the trial excluded women with nonpalpable, mammographically detectedlesions or very small tumors, the appropriateness of chemotherapy in thesesubgroups 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 andfluorouracil followed by leucovorin rescue; or tamoxifen plus cyclophosphamide,methotrexate, and fluorouracil.

Women treated with either combination regimen had a significantly higherfive-year disease-free survival rate than those given tamoxifen alone (90%vs 85%; P = .002). A difference in overall survival between women who didand did not receive chemotherapy also has begun to emerge, with five-yearsurvival 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 treatmentfor each comparison . . . the risk was reduced between 25% and 50%,"Dr. Fisher said. In women aged 49 or younger, chemotherapy decreased therisk of treatment failure, distant disease, and death by about 50%, hesaid. Although the magnitude of risk reduction was somewhat smaller inwomen over 50, they, too, derived benefit from the addition of chemotherapy.

Node Dissection Questioned

One controversial implication of NSABP-B-20 relates to the necessityof performing lymph node dissection. "The current findings eliminatethe need for knowing axillary status in order to make decisions regardingthe use of systemic therapy," Dr. Fisher said.

Another reason for dissecting the nodes--helping to determine prognosis--mayeventually be rendered obsolete by new predictors, he said at a press briefing.Likewise, the use of node dissection to achieve better local control maybe supplanted by other therapies, such as tamoxifen and chemotherapy. Suchfindings, 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 prognosticmarkers fail to differentiate between women who will and will not benefitfrom chemotherapy, and concurred that most women with breast cancer probablyshould receive chemotherapy. However, he warned that the indiscriminateuse of chemotherapy has the potential for "substantial overtreatmentwith toxicity."

The trial, he said, probably represents the "end of the road"for large, indiscriminate chemotherapy trials. Instead, he argued, researchersneed to incorporate predictive diagnostic tests into chemotherapy trials,in order to select and optimize adjuvant therapy.