Pathologic Response and Microvascular Surface Area in Breast Cancer Treated with Neoadjuvant Chemotherapy
AD Corben, R Abi-Raad, R Boutrus, DC Sgroi, A Taghian, EF Brachtel. Massachusetts General Hospital, Boston, MA
Background: Breast cancer may be treated with neoadjuvant chemotherapy (NACT) to reduce locally advanced disease and evaluate response to treatment. Chemotherapy-induced response ranges from complete to absent, and is assessed histologically after excision. Vascular parameters such as microvessel density (MVD) and microvascular surface area (MVSA) may be associated with the tissue response to chemotherapeutic agents, but their role is not well defined.
Design: 62 patients enrolled in a phase II clinical trial for sequential NACT with doxorubicin (A) and paclitaxel (T) were randomized into two groups (A/T and T/A). H&E sections of tumors were examined from all patients before, during and after treatment. Pathologic response evaluation included size, cellularity, viability, histologic type and grade of residual carcinoma, and lymph node metastases. Tumors were assessed following NSABP-B18, Miller-Payne Grade system (MPG), Modified Nottingham Prognostic Index (MNPI), and Sataloff post-treatment pathologic evaluation. Immunohistochemical staining for the vascular marker CD31 was done on 10 representative samples (5 from each group). MVD was calculated at magnification x200, and MVSA  determined by Image J software.
Results: Tumor size decreased from 3 (2.8) cm mean (median) before treatment, to 1.9 (1.5) cm after treatment. NSABP-B18 pathological response was complete in 9%, partial in 68% and none in 23%. 39% of cases showed 30-90% tumor cell reduction (MPG-3), 19% no reduction (MPG-1) and 7% no invasive tumor cells (MPG-5). Lymph nodes were negative in 49% (Sataloff N-A, N-B); nodal metastases with (N-C) and without treatment effect (N-D) were present in 21% and 30%. 96% of residual tumors appeared viable; 38% showed mitoses. MNPI was most favorable for 57%. MVSA decreased from 253 to 872 in group A/T, and increased from 50 to 1452 in group T/A. Average MVD was 13 and 16/field before NACT, 17 and 19/field after NACT in groups A/T and T/A, respectively.
Conclusions: This morphometric study shows MVSA to be variable in sequential chemotherapy regimens with paclitaxel and doxorubicin. This finding contrasts with stable MVD and overall decrease of tumor cellularity. While it is still unclear how certain chemotherapeutic drugs may influence vascular patency and possibly drug delivery, this study supports that vascular dynamics and pathological response both are important factors in the effects of chemotherapy.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 25, Monday Morning