O(6)-methylguanine-DNA methyl transferase gene expression and prognosis in breast carcinoma.

O(6)-methylguanine-DNA methyl transferase (MGMT) in human carcinomas has been associated with tumor resistance to alkylating agents. The aims of this study were: i) to correlate tumor MGMT expression and patient and tumor characteristics in malignant breast carcinomas treated with induction chemotherapy including cyclophosphamide (CPM) and ii) to study the predictive and prognostic values of tumor MGMT gene expression. We used RT-PCR to measure the levels of tumor MGMT expression in 107 patients with breast carcinomas prior to neoadjuvant chemotherapy. Sixty patients (56%) received anthracyclines and CPM and 47 (44%) received only anthracyclines. Low levels of MGMT expression correlated with Scarff-Bloom-Richardson grade III (p<0.005), elevated S-phase (p<0.05), negative estrogen receptors (p<0.05), metastatic status (p<0.05) and occurrence of death (p=0.01). MGMT expression was not predictive of treatment response. Unexpectedly, survival was longer when tumor MGMT expression was high (p<0.005). The 4-year survival rate was 76% for high level MGMT patients and only 55% for others. This difference is also significant using the COX model (p<0.05). In breast cancer, tumor MGMT expression was not predictive of response to CPM. A low MGMT expression was significantly related to poor survival.

Single static view 99mTc-sestamibi scintimammography predicts response to neoadjuvant chemotherapy and is related to MDR expression.

We examined the relevance of a pre-treatment single static view 99mTc-sestamibi scintimammography and expression of multidrug resistance proteins as predictors of response to neoadjuvant chemotherapy for invasive breast cancer. Forty-five patients affected by primary breast cancer underwent clinical examination, mammography, sonography, 99mTc-sestamibi scintimammography, and biopsy for histopathological diagnosis before neoadjuvant chemotherapy. Expression of MDR1 and MRP mRNA were determined by RT-PCR on fine-needle aspirations. Following completion of anthracycline-based chemotherapy, clinical, mammographic, sonographic and pathological responses were determined. 99mTc-sestamibi scintimammography predicted the reduction of tumor size measured by sonography and the pathological response according to Sataloff classification (p<0.05) and tend to predict pathological response according to Chevallier (p<0.1). A negative 99mTc-sestamibi scintimammography predicted chemoresistance with a specificity of 100%. Uptake of 99mTc-sestamibi was inversely correlated to the expression of MDR1 (p<0.05) in invasive ductal carcinoma. A pre-treatment single-view 99mTc-sestamibi scintimammography is an excellent predictor of MDR1 chemoresistance and was highly specific of a lack of pathological response to chemotherapy.