Pathological assessment of response to induction chemotherapy in breast cancer.

Macroscopic and microscopic pathology review was used to assess the degree of tumor reduction after preoperative chemotherapy in 90 patients with inflammatory and locally advanced breast cancer. Fifteen (17%) patients had no evident residual macroscopic tumor on gross pathological examination, and 6 of these 15 had no residual tumor on microscopic review either. There was no significant difference in disease-free and overall survival between the six patients with no microscopic disease and the nine patients with only microscopic residual disease but no residual macroscopic tumor. These 15 patients with major reduction after induction chemotherapy had a longer disease-free survival (DFS) (median not reached at 5 yr) than the other 75 patients with lesser degrees of tumor reduction (DFS = 22 mo; P less than 0.01). Clinical evaluation of response to chemotherapy was a less accurate predictor of outcome than was the pathological assessment of response. Complete clinical responders had a 4-yr DFS of 55%, whereas patients with non macroscopic residual tumor following preoperative chemotherapy, less than one-half of whom had been judged to be a complete clinical responder, had a median DFS of greater than 60 mo and a 4-yr DFS of 75%. Patients whose mastectomy specimen had no macroscopic residual disease had a 93% 5-yr survival compared to patients with a less marked response to therapy who had a 5-yr survival of 30% (P less than 0.01). No pretreatment patient or tumor-related variables correlated with the degree of tumor reduction following preoperative therapy. Achievement of a mastectomy specimen free of residual macroscopic tumor after preoperative chemotherapy is an excellent prognostic factor for a prolonged DFS and survival. This information should be considered in the selection of postoperative systemic therapy.

In vitro stimulation of specific RNA polymerase II-mediated transcription by the pseudorabies virus immediate early protein.

Nuclear extracts from human cells infected with pseudorabies virus (PRV) exhibited higher levels of accurate transcription of RNA polymerase II genes than did control extracts from mock-infected cells. Stimulation was maximal at low DNA concentrations and was not gene-specific. It was heat sensitive in extracts from cells infected with a virus containing a temperature sensitive mutation in the immediate early (IE) gene. The stimulatory activity copurified from the IE protein and was also heat sensitive when purified with cells infected with tsG, further indicating that the IE protein was responsible for this stimulation. These results thus demonstrate an in vitro system that mimics, at least in part, the in vivo stimulatory action of the PRV IE protein. They further imply that the IE protein acts not by increasing the amounts of cellular transcription factors, but rather by directly or indirectly altering their activities.

A phase II trial of PCNU in patients with malignant melanoma and central nervous system metastases.

Twelve patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with PCNU. All patients had prior chemotherapy and/or radiation therapy and had progressive brain metastases, documented by computerized tomography. PCNU was given as a single intravenous infusion of 90-110 mg/m2 every 6-8 weeks. There was one partial response and four patients had stable disease. Although no episodes of sepsis or bleeding occurred, seven of 17 courses led to significant granulocytopenia or thrombocytopenia. Nonhematopoietic toxicities were mild. These results indicate that systemic PCNU is unlikely to be more effective than other currently used chemotherapy in patients with malignant melanoma and CNS metastases.

High-dose 1-beta-D-arabinofuranosylcytosine in advanced breast cancer.

Twenty-two patients with metastatic breast cancer refractory to conventional chemotherapeutic agents were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C) at a dose of 2 g/m2 over 2 h every 12 h for 3 doses at 21-day intervals. Two patients achieved partial remission, 3 patients had less than partial response.