Pathologic Response and Tumor Thickness at Tumor-Normal Interface (TNI): Potential Prognostic Factors of Disease-Free Survival (DFS) in Liver Metastases of Breast Cancer (LMBC).
Jane Zhou, Daniel Rosen, Antoine Brouquet, Daniel Abbott, Evelyne M Loyer, Funda Meric-Bernstam, Henry M Kuerer, Steven A Curley, Eddie K Abdalla, Kelly K Hunt, Jean-Nicolas Vauthey, Aysegul Sahin, Dipen Maru. The University of Texas M.D.Anderson Cancer Center, Houston
Background: Pathologic response to preoperative chemotherapy defined as percentage of residual tumor cells and tumor thickness at TNI are independent predictors of survival in hepatic colorectal metastases. Pathologic predictors of survival after resection of LMBC are unknown. This study evaluated these two parameters by blinded independent review and correlated them with DFS.
Design: Thirty eight patients (average age 43 yrs. range 25-63 yrs., 2000-2010) who underwent resection of LMBC after preoperative chemotherapy were analyzed. H&E sections from LMBC were independently reviewed by two pathologists (JZ, DR) who were blinded to the clinical data and patient outcomes. The pathologic response was defined as complete (no tumor cells)/major (<50% residual tumor cells), or minor (≥50% residual tumor cells). The maximum thickness of uninterrupted tumor cells was measured perpendicular to the TNI. Other parameters including tumor size, margin status and clinical parameters including radiologic response using RECIST criteria, survival outcome were derived from the surgical oncology database. ROC analysis was used to determine the ability of TNI to predict pathologic response. Kappa statistics were used to determine interobserver agreement of pathologic response and TNI criteria between pathologists. Univariate analysis was used to determine predictors of DFS.
Results: The mean ± SD for number of LMBC was 1.6 ± 1.8, and mean ± SD for tumor size was 2.4 ± 2 cm. Twenty-seven patients (71%) had complete or partial radiologic response. Pathologic response to chemotherapy by residual tumor cell category was major in 16 (including complete in 11) and minor in 22 patients. Mean ± SD tumor thickness at TNI was 3.9 ± 4.1 mm and 17 patients had tumor thickness at TNI > 3 mm. Interobserver agreement was good among two pathologists for both pathologic response (k = 0.87) and TNI assessments (k = 0.49). TNI predicted pathologic response with excellent accuracy (AUROC = 0.974). There was a trend toward association of complete/partial radiologic response with major pathologic response (p = 0.07) and with tumor thickness at TNI (p = 0.07). By univariate analyis, positive surgical margins (p < 0.001), tumor size > 5cm (p = 0.001), TNI > 3 mm (p = 0.04), and minor pathologic response (p = 0.04) were associated with worse DFS.
Conclusions: Tumor size, pathologic response, tumor thickness at TNI and positive margin are potential predictors of DFS after resection of LMBC and should be studied in a larger patient population.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 38, Tuesday Morning