Metastatic axillary node ratio predicts recurrence and poor long-term prognosis in patients with advanced stage IIIC (pN3) breast cancer

PURPOSE: Patients with stage IIIC breast cancer are classified as having pathologic nodal stage 3 (pN3) according to the 7th American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) staging system. However, the prognosis of patients with this stage is still highly variable. This study was carried out to investigate the validity of metastatic axillary lymph node ratio (mALNR) as a predictor of long-term prognosis in stage IIIC breast cancer. METHODS: Medical records of 297 patients who underwent surgery with more than level II axillary dissection for breast cancer and who were diagnosed with pN3 by pathology between 1990 and 2010, were reviewed. Clinicopathologic variables were evaluated as prognostic factors of disease-free and overall survival by univariate and multivariate analyses. RESULTS: A preliminary analysis revealed the cutoff value of mALNR to be 0.65 (Low65 group vs. High65 group). The mean mALNR was 0.62 (0.16–1.0) and was the most significant independent predictor of disease-free and overall survival on multivariate analysis. The rates of recurrence were significantly different according to mALNR (Low65, 40.3%; High65, 63.0%; P < 0.001). The 10-year disease-free (Low65, 57.0%; High65, 35.0%) and overall (Low65, 64.2%; High65, 38.3%) survival rates decreased significantly with increased mALNR (P < 0.001). CONCLUSION: Patients with stage IIIC breast cancer can be subdivided into subgroups with significantly different long-term prognoses. Our data suggest that the mALNR is an independent risk factor of recurrence and mortality. The mALNR is a valuable prognostic factor to predict the long-term prognosis of stage IIIC breast cancer patients.

The Usefulness of Intraoperative Circumferential Frozen-Section Analysis of Lumpectomy Margins in Breast-Conserving Surgery / 한국유방암학회지

PURPOSE: Intraoperative frozen-section analysis of the lumpect-omy margin during breast-conserving surgery (BCS) is an excellent method in obtaining a clear resection margin. This study aimed to investigate the usefulness of intraoperative circumferential frozen-section analysis (IOCFS) of lumpectomy margin during BCS for breast cancer, and to find factors that increase the conversion into mastectomy. METHODS: From 2007 to 2011, 509 patients with breast cancer underwent IOCFS during BCS. The outer surfaces of the shaved lumpectomy margins were evaluated. A negative margin was defined as no ink on the tumor. All margins were evaluated using the permanent section analysis. RESULTS: Among the 509 patients, 437 (85.9%) underwent BCS and 72 (14.1%) finally underwent mastectomy. Of the 483 pathologically confirmed patients, 338 (70.0%) were true-negative, 24 (5.0%) false-negative, 120 (24.8%) true-positive, and 1 (0.2%) false-positive. Twenty-four patients (4.7%) among total 509 patients had undetermined margins as either atypical ductal hyperplasia or ductal carcinoma in situ in the first IOCFS. The IOCFS has an accuracy of 94.8% with 83% sensitivity, 99.7% specificity, 93.4% negative predictive value, and 99.2% positive predictive value. Sixty-three cases (12.4%) were converted to mastectomy, the first intraoperatively. Of the 446 (87.6%) patients who successfully underwent BCS, 64 patients received additional excisions and 32 were reoperated to achieve clear margin (reoperation rate, 6.3%). Twenty-three of the reoperated patients underwent re-excisions using the second intraoperative frozen section analysis, and achieved BCS. Nine cases were additionally converted to mastectomy. No significant differences in age, stage, and biological factors were found between the BCS and mastectomy cases. Factors such as invasive lobular carcinoma, multiple tumors, large tumor, and multiple excisions increased the conversion to mastectomy. CONCLUSION: The IOCFS analysis during BCS is useful in evaluating lumpectomy margins and preventing reoperation.

The Role and Regulatory Mechanism of 14-3-3 Sigma in Human Breast Cancer / 한국유방암학회지

PURPOSE: 14-3-3 sigma (sigma) is considered to be an important tumor suppressor and decreased expression of the same has been reported in many malignant tumors by hypermethylation at its promoter or ubiquitin-mediated proteolysis by estrogen-responsive ring finger protein (Efp). In this study, we investigated the significance of 14-3-3 sigma expression in human breast cancer and its regulatory mechanism. METHODS: Efp was silenced using small interfering RNA (siRNA) in the MCF-7 breast cancer cell line in order to examine its influence on the level of 14-3-3 sigma protein. The methylation status of the 14-3-3 sigma promoter was also evaluated by methylation-specific polymerase chain reaction (PCR). The expression of Efp and 14-3-3 sigma in 220 human breast carcinoma tissues was assessed by immunohistochemistry. Other clinicopathological parameters were also evaluated. RESULTS: Silencing Efp in the MCF-7 breast cancer cell line resulted in increased expression of 14-3-3 sigma. The Efp-positive human breast cancers were more frequently 14-3-3 sigma-negative (60.5% vs. 39.5%). Hypermethylation of 14-3-3 sigma was common (64.9%) and had an inverse association with 14-3-3 sigma positivity (p=0.072). Positive 14-3-3 sigma expression was significantly correlated with poor prognosis: disease-free survival (p=0.008) and disease-specific survival (p=0.009). CONCLUSION: Our data suggests that in human breast cancer, the regulation of 14-3-3 sigma may involve two mechanisms: ubiquitin-mediated proteolysis by Efp and downregulation by hypermethylation. However, the inactivation of 14-3-3 sigma is probably achieved mainly by hypermethylation. Interestingly, 14-3-3 sigma turned out to be a very significant poor prognostic indicator, which is in contrast to its previously known function as a tumor suppressor, suggesting a different role of 14-3-3 sigma in breast cancer.