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Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are the key factors mediating neo-vascularization. They are often coexpressed in breast cancer. Sex steroids may stimulate angiogenesis via the estrogen receptor (ER) pathway. We investigated to compare the effects of the addition of tamoxifen to epirubicin versus epirubicin alone on VEGF and VEGFR2 expression in breast cancer patients. The expression of VEGF and VEGFR2 was assessed on tissue microarray by immunohistochemistry at baseline conditions and after treatments in the case of 191 patients with T2-4 N0-1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin plus tamoxifen as primary systemic treatment. Epirubicin alone failed to induce changes in VEGF expression (P = 0.54), while the addition of tamoxifen to epirubicin resulted in a significant reduction in VEGF expression (P < 0.001). As a consequence, baseline VEGF had a negative prognostic role in patients who received epirubicin alone but not in patients receiving epirubicin plus tamoxifen (interaction test P < 0.05). VEGFR2 expression increased at residual tumor histology in both treatment arms, with a lesser extent in patients receiving tamoxifen plus epirubicin. Decrease in VEGFR2 expression was significantly associated with response rate (P = 0.02). The addition of tamoxifen to epirubicin resulted in a suppression of a key angiogenic pathway. These data suggest a potential synergism of these two drugs.

Purpose: To investigate whether magnetic resonance imaging (MRI) is superior to clinical palpation in the assessment of response of breast cancer to primary chemotherapy (PC)., Patients and Methods: Seventy-three patients with T2-4, N0, M0 breast cancer were treated with 3-4 cycles of single agent epirubicin before definitive surgery. MRI was performed at baseline condition and at the end of chemotherapy., Results: According to the WHO criteria, 20 (27.4%) patients attained a complete response (CR) by clinical palpation and 41 (56.2%) a partial response. The corresponding response rate by MRI was 11 (15.1%) and 34 (46.6%), respectively. Residual tumor assessed by MRI better correlated with pathologic measurements (Spearman r : 0.72) than residual tumor assessed by clinical palpation (Spearman r : 0.58). Post-chemotherapy histology evaluation revealed pathologic CR in three cases, only one of them was considered as complete responder by MRI. Residual disease consisted in in situ carcinoma in four cases, one of them was complete responder at MRI, the remaining three showed residual abnormal contrast enhancement indistinguishable from that of invasive tumors., Conclusions: As compared to pathology specimens, MRI is able to represent the extent of cancer more accurately than clinical palpation. It constitutes a promising technique in assessing the BC response to PC. The current limit of MRI is the scarce specificity in predicting the nature of residual disease., (Copyright 2004 Kluwer Academic Publishers)

The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0) submitted to primary chemotherapy. A low relationship was recorded between tumor size assessed clinically and that evaluated by either mammography: Spearman R = 0.38 or echography: R = 0.24, while a greater correlation was found between the tumor dimension obtained by the two imaging techniques (R = 0.62). According to the WHO criteria, the grade of response of breast cancer to primary chemotherapy, showed by mammography and echography, was less marked than the grade of response seen at clinical examination. Residual tumor size assessed clinically depicted a stronger correlation with pathological findings (R = 0.68) than the residual disease assessed by echography (R = 0.29) and mammography (R = 0.33). Post-chemotherapy histology evaluation revealed pathological complete response in three cases (2.1%). Two of these cases were judged as complete responders by clinical palpation but only one was recognized by mammography, and none by echography. Clinical response, but not the response obtained by the two imaging techniques, was a significant predictor for longer disease free survival (p = 0.04). To conclude, physical examination measurements remain the method of choice in evaluating preoperatively the disease response in trials of primary chemotherapy. Prediction of pathological outcome is not improved by echography and mammography.