Evolving Role for Preoperative Chemo in Breast Cancer

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 response.

"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 postoperatively.

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 tumor response.