AMELIA ISLAND, Fla--Systemic chemotherapy has emerged as an integral
part of the treatment of operable breast cancer. Now, researchers are
investigating whether variations in the timing of chemotherapy may
further influence patient outcomes.
"It is important to evaluate these issues of timing and
specifically consider the advantages of preoperative
chemotherapy," Terry Mamounas, MD, medical director, Mt. Sinai
Center for Breast Health, Cleveland, said at the 11th annual meeting
of the Southern Association for Oncology.
Giving chemotherapy before breast cancer surgery results in shrinkage
of primary tumors, allowing more patients to be candidates for
breast-conserving surgery. But more important from a clinical
standpoint, he said, preoperative chemotherapy separates patients
into different groups, based on their clinical and pathologic tumor
"A correlation between tumor response with preoperative
chemotherapy and relapse-free survival has been suggested by earlier
studies and confirmed by recent larger prospective clinical
trials," he said. "That means that response to preoperative
chemotherapy can be used as a prognostic marker for outcomes and as a
guide to choosing further loco-regional and systemic therapy."
Results of NSABP B-18
A 1988 National Surgical Adjuvant Breast Project randomized trial
(NSABP B-18) sought to determine whether preoperative chemotherapy
with AC (Adriamycin/cyclophosphamide) more effectively prolonged
disease-free and overall survival than the same regimen given
Of the preoperative patients, 36% had a complete response and 43% had
a partial response, for an overall response rate of 79%. Of those
with a complete response, 9% had no tumor present at surgery and 4%
had nonin-vasive tumors.
There was also clear evidence that preoper-ative chemotherapy
resulted in pathologic axillary lymph node down-staging: 58% of
patients receiving postoperative chemotherapy had positive axillary
nodes at surgery vs 40% of the preoperative chemotherapy patients.
In addition, preoperative patients were more likely to receive
breast-conserving surgery than patients getting postoperative
chemotherapy. There was, however, no difference in survival rates
between the two groups.
"The role of preoperative chemotherapy is still evolving,"
Dr. Mamounas concluded, "but according to these results,
preoperative chemotherapy may be considered as an alternative
treatment, since it results in equivalent outcomes, compared with
postoperative chemotherapy, and also offers response information that
could be used as an intermediate endpoint and a guide for future therapy."
Subgroups Might Benefit
He suggested, for example, that subgroups of patients with high
likelihood of pathologic complete tumor response after preoperative
chemotherapy could perhaps be spared radiation or surgical resection.
Finally, he said, response to preoperative chemotherapy, in addition
to serving as a prognostic marker itself, could play a role in
determining the value of other tumor markers.
"Serially monitoring tumor marker changes during preoperative
chemotherapy may provide biologic insight into the nature and
function of proven prognostic tumor markers," Dr. Mamounas said,
including their prognostic value for disease-free and overall
survival and their predictive value for clinical and path-ologic