Factors associated with disease upgrading in patients with papillary breast lesion in core-needle biopsy.

BACKGROUND: Traditionally, surgical excision is recommended for benign papillary lesions in core-needle biopsy (CNB) because of their malignant potency. The aim of this study was to identify factors associated with disease upgrading to malignancy in patients with benign papillary lesions in CNB. METHODS: A total of 179 female patients were evaluated retrospectively who were diagnosed as having a benign papillary lesion in CNB and underwent a subsequent surgical excision between January 2007 and December 2016. Ultrasonography-guided CNB was performed using a 14-gauge needle gun method. RESULTS: The rate of upgrade to malignancy was 10.6% (7.6% in papillary lesions without atypia vs. 33.3% in papillary lesions with atypia; P=0.001). The univariable analysis revealed that older age at diagnosis (≥50 years old), menopause, lesion size on ultrasonography, palpability, multifocality, and atypia in CNB were associated with upgrading. The multivariable analysis revealed that age ≥50 years (OR, 4.6; 95% CI, 1.5-14.1; P=0.008), lesion size of ≥2 cm (OR, 6.4; 95% CI, 1.9-21.1; P=0.002), and atypia in CNB (OR, 5.1; 95% CI, 1.5-18.2; P=0.011) were significantly associated with upgrading to malignancy. CONCLUSIONS: Upgrading to malignancy in patients with benign papillary lesions in CNB was associated with age ≥50 years, lesion size ≥2 cm, and atypia in CNB.

Parity Differently Affects the Breast Cancer Specific Survival from Ductal Carcinoma In Situ to Invasive Cancer: A Registry-Based Retrospective Study from Korea.

PURPOSE: Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma. METHODS: We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC. RESULTS: The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group (P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients (P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04). CONCLUSIONS: Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.

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

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.

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 role and regulatory mechanism of 14-3-3 sigma in human breast cancer.

PURPOSE: 14-3-3 sigma (σ) 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 σ 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 σ protein. The methylation status of the 14-3-3 σ promoter was also evaluated by methylation-specific polymerase chain reaction (PCR). The expression of Efp and 14-3-3 σ 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 σ. The Efp-positive human breast cancers were more frequently 14-3-3 σ-negative (60.5% vs. 39.5%). Hypermethylation of 14-3-3 σ was common (64.9%) and had an inverse association with 14-3-3 σ positivity (p=0.072). Positive 14-3-3 σ 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 σ may involve two mechanisms: ubiquitin-mediated proteolysis by Efp and downregulation by hypermethylation. However, the inactivation of 14-3-3 σ is probably achieved mainly by hypermethylation. Interestingly, 14-3-3 σ 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 σ in breast cancer.

Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea--a report from the Korean Breast Cancer Society.

PURPOSE: Breast cancer in very young women (age < 35 years) is uncommon and poorly understood. We sought to evaluate the prognosis and treatment response of these patients compared with women ages 35 to 50 years. PATIENTS AND METHODS: We analyzed data from 9,885 breast cancer patients age < or = 50 years who were part of the Korean Breast Cancer Society registration program between 1992 and 2001. The overall survival (OS) and breast cancer-specific survival (BCSS) were compared between age groups. RESULTS: One thousand four hundred forty-four patients (14.6%) were younger than age 35 and 8,441 (85.4%) patients were between 35 and 50 years of age. Younger patients had significantly higher T-stage and higher lymph node positivity and lower hormone receptor expression than older patients. Younger patients had a greater probability of death than older patients, regardless of tumor size or lymph node status. The survival difference was significant for patients with positive or unknown hormone receptor status (P < .0001), but not for patients with negative hormone receptor status. In a multivariate analysis, the interaction term of young age and hormone receptor positivity was significant for OS and BCSS with a hazard ratio for OS of 2.13 (95% CI, 1.52 to 2.98). The significant survival benefit from adjuvant hormone therapy after chemotherapy observed in older patients (hazard ratio for OS, 0.61; 95% CI, 0.47 to 0.79; P = .001) could not be seen in younger patients (P > .05). CONCLUSION: Younger patients (age < 35) showed worse prognosis than older patients (age, 35 to 50 years) only in the hormone receptor-unknown or hormone receptor-positive subgroups. Adjuvant tamoxifen therapy might provide less survival benefit when added to chemotherapy in very young breast cancer patients.

The significance of c-erbB-2 overexpression and p53 expression in patients with axillary lymph node--negative breast cancer: a tissue microarray study.

We conducted this study to examine whether the expression of c-erbB-2 and p53 is the prognostic indicator for patients with early-stage breast cancer in which axillary lymph node metastasis is absent. We examined 326 patients with early-stage breast cancer in which axillary lymph node metastasis is absent. Tissue microarrays were constructed. Following this, immunohistochemical staining was done for estrogen receptor (ER), progesterone receptor (PR), c-erbB2, and p53. The results were as follows: (1) expression of c-erbB-2 was correlated with other clinicopathologic factors (eg, patient's age, presence of menopause, tumor size, histologic and nuclear grade, and presence of hormone receptors such as ER and PR); and (2) expression of p53 was correlated with survival rate, patient's age, presence of menopause, and tumor size. However, these results were not statistically significant. In conclusion, our results indicate that expression of c-erbB-2 and p53 did not have any prognostic value in patients with early-stage breast cancer in which axillary lymph node metastasis is absent.

Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-beta (ERbeta) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERbeta in BC development and progression. ERbeta expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERbeta mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERbeta mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERbeta expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERbeta expression. Collectively, ERbeta mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.