ASCO--A brief, intensive preoperative chemotherapeutic regimen failed
to improve breast cancer survival over conventional adjuvant chemotherapy
in a 1,500-patient randomized trial, Dr. Eleftherios Mamounas said for
the National Surgical Adjuvant Breast Project (NSABP). However, preoperative
treatment often resulted in complete clinical remission prior to surgery.
Moreover, Dr. Mamounas said, the initial response to preoperative chemotherapy
correlated with disease-free survival, suggesting that preoperative treatment
may provide useful prognostic information to guide follow-up therapy.
The NSABP investigators compared the efficacy of short-term intensive
preoperative chemotherapy with doxorubicin (60 mg/m²) and cyclophosphamide
(600 mg/m²) given every three weeks for four cycles versus the same
regimen after surgery. Women age 50 or older also received tamoxifen (Nolvadex).
About half the patients in each treatment arm were age 49 or younger
at enrollment, and a quarter were ages 50 to 59. Roughly three fourths
of the patients were node negative, and 25% to 30% had tumors smaller than
2 cm; 13% had tumors larger than 5 cm.
"The primary purpose of the study was to determine if preoperative
chemotherapy, as opposed to postoperative chemotherapy, will be more effective
in terms of disease-free survival and overall survival in patients who
have operable breast cancer," Dr. Mamounas said.
Secondary aims related to clinical and pathological responses to preoperative
chemotherapy and to the ability of preoperative therapy to downstage axillary
nodes and increase lumpectomy rates. The investigators also wanted to see
whether tumor response to preopera-tive chemotherapy correlated with disease-free
or overall survival.
At a mean follow-up of six years, patients in each treatment arm had
a 67% disease-free survival rate and 80% overall survival rate, Dr. Mamounas
Preoperative chemotherapy did result in nodal downstaging, as 60% of
patients had negative nodes at surgery versus 42% of patients who had conventional
adjuvant chemotherapy. Preoperative therapy also was associated with a
higher rate of lumpectomy, 68% versus 60%.
Notably, 249 patients given preopera-tive chemotherapy had complete
clinical remissions prior to surgery. In 63 of these patients, no evidence
of tumor could be found on histologic examination of specimens. Another
26 patients had only ductal carcinoma in situ (DCIS).
Evaluation of disease-free survival by initial response to preoperative
chemotherapy revealed a correlation. Disease-free survival exceeded 80%
in the 89 patients who had complete remissions or residual DCIS, but was
about 70% or less in patients who had responses other than complete response
or DCIS after preoper-ative chemotherapy. A similar pattern emerged for
overall survival. The two treatment arms did not differ with respect to
site of first recurrence.
"In patients with operable breast cancer, preoperative chemotherapy
is safe and results in high rates of clinical tumor response and increased
rates of breast preservation," Dr. Mamounas said. "When compared
to postoperative chemotherapy, preoperative treatment results in equivalent
disease-free survival, distant disease-free survival, and overall survival."
On the basis of these results, he continued, "preoperative chemotherapy
may be considered an alternative to standard adjuvant chemotherapy in patients
who are candidates for chemotherapy."
Dr. Mamounas said that the results have led NSABP investigators to launch
another clinical trial to explore the effects of preoperative chemotherapy.
The trial will randomize patients to the doxorubicin-cyclophosphamide combination,
followed by surgery or followed by preoperative or postoperative administration
of docetaxel (Taxotere).
"Preoperative chemotherapy results in equivalent overall and disease-free
survival, and provides additional information that can be useful to guide
further systemic and local intervention," he said. "We plan to
pursue this finding in the upcoming trial."
The purpose of the new trial, he said, is to see whether the addition
of a taxane will prolong disease-free survival and overall survival, and
increase clinical and pathological response rates, rates of axillary node
downstaging, and breast preservation.