BETHESDA, MdAdjuvant therapy should be offered as an option
to node-negative breast cancer patients, even those with tumors smaller than 1
cm, said Bernard Fisher, MD, scientific director of the National Surgical
Adjuvant Breast and Bowel Project (NSABP).
At the National Institutes of Health (NIH) Consensus
Development Conference on Adjuvant Therapy for Breast Cancer, Dr. Fisher
reviewed progress made in NSABP studies on early-stage breast cancer since the
first NIH consensus conference on the subject in 1985.
In 1985, the panel recommended no therapy other than surgery
for breast cancer patients with no lymph node involvement. By the next
conference, in 1990, new trial results convinced the consensus panel that the
likelihood of a recurrence decreased in node-negative breast cancer with
adjuvant combination chemotherapy or with adjuvant tamoxifen (Nolvadex) in
node-positive patients. But the panel stated that patients with tumors of 1 cm
or less had an excellent prognosis and did not require adjuvant therapy outside
of clinical trials.
In 1990, questions remained regarding the effects of tamoxifen
in estrogen-receptor (ER)-negative tumors, and about combination chemotherapy
plus tamoxifen in ER-positive, node-negative breast cancer. Ten years later,
data from six NSABP randomized trials with 11,620 node-negative patients and 8
to 14 years of follow-up are confirming some of the earlier panels’
conclusions, refuting others, and answering the previously unanswerable
questions, Dr. Fisher said.
For ER-negative, node-negative breast cancer, improvements in
disease-free survival and overall survival have persisted in the NSABP B-13
trial for 14 years with use of methotrexate followed by 5-fluorouracil and
leucovorin (M->F) and, in NSABP B-19, for 8 years with use of
cyclophosphamide/methotrexate/fluorouracil (CMF). CMF is clearly better for
women under age 50, Dr. Fisher said.
A later study, NSABP B-23, compared four treatments: CMF plus
placebo; CMF plus tamoxifen; doxorubicin (Adriamycin) and cyclophosphamide
(AC) plus placebo; and AC plus tamoxifen. After 5 years of follow-up, no
significant differences in relapse-free survival, event-free survival, or
overall survival were found among the four groups. Tamoxifen provided no
benefit for these ER-negative patients.
Dr. Fisher reviewed results of NSABP B-14, which studied 5
years of tamoxifen for node-negative patients with positive estrogen receptors.
With data now 14 years out, he said, "in young and old, tamoxifen
works." Benefit was not enhanced when tamoxifen therapy was extended
beyond 5 years.
To improve on tamoxifen’s therapy, NSABP B-20 tested
tamoxifen alone vs tamoxifen with M->F or CMF in ER-positive patients. At
8 years of follow-up, chemotherapy significantly improved disease-free as well
as overall survival.
Recently reported results from NSABP B-21 indicate that
tamoxifen cannot replace radiation after lumpectomy for controlling ipsilateral
breast tumor recurrence (IBTR) in patients with tumors 1 cm or less, Dr. Fisher
For women who received tamoxifen alone, the rate of IBTR was
23.3 per 1,000 patients per year. Those who received radiation therapy plus
placebo had a recurrence rate of 11.7 per 1,000 patients. The recurrence rate
for women who received radiation therapy plus tamoxifen was 3.4 per 1,000
patients per year.
With the expanding use of screening mammography, more women are
being diagnosed with tumors 1 cm or smaller. Dr. Fisher reviewed a combined
analysis of five NSABP randomized trials in patients with small tumors. At 8 years, in ER-negative patients, recurrence-free survival
improved by almost 10 percentage points when chemotherapy was added after
surgery; overall survival was similar in both groups. For patients with
ER-positive tumors, tamoxifen plus chemotherapy significantly improved both
recurrence-free survival and overall survival, he noted.
"As the prognosis for breast cancer becomes better,
treatment decisions become more difficult," Dr. Fisher said. Women may
have a sufficiently good prognosis that negates the need for treatment, but
knowing who should defer adjuvant treatment is difficult.
Dr. Fisher concluded that prognosis, although favorable, is not
sufficiently so for all women with tumors 1 cm or smaller to warrant dismissing
systemic therapy as a possible option.
Based on presentations by Dr. Fisher and others, the November
2000 NIH consensus panel stated that, for women with tumors 1 cm or smaller,
the decision to consider chemotherapy should be individualized.
The panel concluded that adjuvant hormonal therapy is
appropriate for ER-positive patients, regardless of tumor size, but that
premenopausal women with tumors less than 10 mm in size who wish to avoid the
symptoms of estrogen deprivation may decide against taking the