Impact of residual microcalcifcations on prognosis after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Hormone Receptor Subtype in Ductal Carcinoma in Situ: Prognostic and Predictive Roles of the Progesterone Receptor.

BACKGROUND: We investigated the prognostic and predictive roles of the hormone receptor (HRc) subtype in patients with ductal carcinoma in situ (DCIS). We focused on identifying the roles of the progesterone receptor (PR) independent of estrogen receptor (ER) status. METHODS: Nationwide data of 12,508 female patients diagnosed with DCIS with a mean follow-up period of 60.7 months were analyzed. HRc subtypes were classified as ER-/PR-, ER-/PR+, ER+/PR-, and ER+/PR+ based on ER and PR statuses. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The ER+/PR+ group showed better prognoses than the ER+/PR- and ER-/PR- groups in the patients who received tamoxifen therapy (p = .001 and p = .031, respectively). HRc subtype was an independent prognostic factor (p = .028). The tamoxifen therapy group showed better survival than the patients who did not receive tamoxifen, but only in the ER+/PR+ subgroup (p = .002). Tamoxifen therapy was an independent prognostic factor (HR, 0.619; 95% CI, 0.423 - 0.907; p = .014). PR status was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy (p < .001), and it remained a prognostic factor independent of ER status (HR, 0.576; 95% CI, 0.349 - 0.951; p = .031). CONCLUSION: The HRc subtype can be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Tamoxifen therapy can improve overall survival in the ER+/PR+ subtype. PR status has significant prognostic and predictive roles independent of ER status. Testing for the PR status in addition to the ER status is routinely recommended in patients with DCIS to determine the HRc subtype in clinical settings. IMPLICATIONS FOR PRACTICE: The hormone receptor (HRc) subtype was an independent prognostic factor, and the estrogen receptor (ER)+/progesterone receptor (PR) + subtype showed a better survival in patients with ductal carcinoma in situ (DCIS) who received tamoxifen therapy. PR was an independent prognostic factor independent of ER, and PR was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy. The HRc subtype could be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Testing of PR status in addition to ER status is routinely recommended for patients with DCIS to determine the HRc subtype in clinical settings.

Mammographic breast density, its changes, and breast cancer risk in premenopausal and postmenopausal women.

BACKGROUND: The risk of breast cancer related to changes in breast density over time, including its regression and persistence, remains controversial. The authors investigated the relationship between breast density and its changes over time with the development of breast cancer in premenopausal and postmenopausal women. METHODS: The current cohort study included 74,249 middle-aged Korean women (aged ≥35 years) who were free of breast cancer at baseline and who underwent repeated screening mammograms. Mammographic breast density was categorized according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). A dense breast was defined as heterogeneously dense or extremely dense, and changes in dense breasts between baseline and subsequent follow-up were classified as none, developed, regressed, or persistent dense breast. RESULTS: During a median follow-up of 6.1 years (interquartile range, 4.1-8.8 years), a total of 803 incident breast cancers were identified. Baseline breast density was found to be positively associated with incident breast cancer in a dose-response manner, and this association did not significantly differ by menopausal status. The multivariable-adjusted hazard ratios (HRs) for breast cancer comparing "heterogeneously dense" and "extremely dense" categories with the nondense category were 1.96 (95% confidence interval [95% CI], 1.40-2.75) and 2.86 (95% CI, 2.04-4.01), respectively. With respect to changes in dense breasts over time, multivariable-adjusted HRs for breast cancer comparing persistent dense breast with none were 2.37 (95% CI, 1.34-4.21) in premenopausal women and 3.61 (95% CI, 1.78-7.30) in postmenopausal women. CONCLUSIONS: Both baseline dense breasts and their persistence over time were found to be strongly associated with an increased risk of incident breast cancer in premenopausal and postmenopausal women. LAY SUMMARY: Both baseline breast density and its changes over time were found to be independently associated with the risk of breast cancer in both premenopausal and postmenopausal women. The risk of incident breast cancer increased in women with persistent dense breasts, whereas the breast cancer risk decreased as dense breasts regressed. The findings of the current study support that both dense breasts at baseline and their persistence over time are independent risk factors for developing breast cancer.

Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study.

The impact of variations in serum thyroid hormone concentration within the euthyroid range on breast cancer risk remains unclear. We investigated the effect of serum thyrotropin (TSH) and thyroid hormone concentration on breast cancer risk. This cohort study involved 62,546 Korean women, aged ≥40 years, who were free of breast cancer at baseline and underwent health examination with determination of free thyroxine (FT4) and TSH. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI). During a median follow-up of 4.8 years (interquartile range: 2.8-7.3 years), 834 incident breast cancers were identified. Compared to normal FT4 level, abnormally high serum FT4 level was associated with an increased risk of incident breast cancer with a corresponding multivariable aHR (95% CI) of 1.98 (1.02-3.83). This association tended to be stronger in postmenopausal women than in premenopausal women. Within the euthyroid range, the highest TSH tertile was associated with a lower risk of breast cancer than the lowest TSH tertile with a corresponding aHR (95% CI) of 0.68 (0.55-0.84). In contrast, highest FT4 tertile was associated with a higher risk of breast cancer than the lowest FT4 tertile. Abnormally high FT4 as well as higher FT4 within the euthyroid range were positively associated with breast cancer risk, while higher TSH concentration within the euthyroid range was negatively associated with breast cancer risk. Our findings indicate that thyroid function within both the abnormal and euthyroid ranges may contribute to the development of breast cancer.

Optimal treatment of breast cancer in women older than 75 years: a Korea Breast Cancer Registry analysis.

PURPOSE: The aim of this study was to investigate the therapeutic efficacy of adjuvant modalities for elderly Asian breast cancer patients using population-based data from the Korean Breast Cancer Registry database. METHODS: We identified 53,582 patients who underwent curative surgery between January 2005 and December 2010. The primary end point was the comparison of overall survival between the administration or omission of adjuvant treatment modalities, including endocrine treatment, radiation therapy, and chemotherapy, in the elderly group (older than 75 years) compared with the control group (younger than 75 years). RESULTS: Of the 53,582 patients analyzed, the total number of elderly patients was 901 (1.7%), and the number of control patients was 52,681 (98.3%). Although elderly patients were found to have larger tumor sizes (p = 0.024) and higher pathological stages (p < 0.001) than the control group, elderly patients were less likely to undergo adjuvant treatment compared to the control group. However, use of endocrine treatment in elderly patients with HR-positive breast cancer is associated with improved overall survival (OS) (adjusted OR 0.417; 95% confidence interval [CI] 0.240-0.726; p = 0.002). Furthermore, chemotherapy was associated with a significant improvement in OS in patients with stage II and III breast cancer (adjusted OR 0.657; 95% CI 0.462-0.934; p = 0.019). CONCLUSION: Endocrine treatment and chemotherapy for elderly patients are associated with improved OS. Therefore, personalized decision-making based on the potential survival benefit of adjuvant treatment modalities should be made with the careful counseling of all elderly patients with breast cancer.

Predictive factors for the presence of invasive components in patients diagnosed with ductal carcinoma in situ based on preoperative biopsy.

BACKGROUND: In patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively. METHODS: Patients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens. RESULTS: Of the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR = 0.26, C.I. = 0.07-0.93, p = 0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR = 2.39, C.I. = 1.05-5.42, p = 0.038 in univariate analysis, HR = 2.86, C.I. = 1.14-7.14, p = 0.025 in multivariate analysis). CONCLUSIONS: Mass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.

Chronologically changing patterns in the survival of korean patients with breast cancer and related clinical factors: a nationwide registry-based study.

PURPOSE: Advances in breast cancer treatment have contributed to marked improvements in patient outcomes over the past three decades. This study aims to chronologically evaluate the survival of patients with breast cancer and investigate the observed changes over time. METHODS: Statistics from the Korean National Cancer Registry, based on all 60,571 patients with invasive breast cancer during the 21 year period, were analyzed. We divided the study interval into four periods (P1: 1988-1992, P2: 1993-1997, P3: 1998-2002, P4: 2003-2008). RESULTS: The patients treated during P4 showed significantly better 5-year overall survival (OS) than did those treated during P1 (5Y OS; P1 = 79.0 vs. P4 = 92.2, p < 0.001). In the multivariate analyses, younger age, mastectomy, high stage, high tumor grade, lymphovascular invasion, and hormone receptor negativity were poor prognostic factors. The multivariate analysis demonstrated that diagnosis periods significantly and independently associated with OS in the overall group of patients. In our analysis of age-period-interaction models, the hazard ratio (HR) for death for patients who were under 35 years of age, compared to those who were older, tended to decrease over time (HR of age < 35 vs. 35 ~ 50; P1 = 0.739, p = 0.007; P2 = 0.744, p < 0.001; P3 = 0.886, p = 0.041; P4 = 0.983, p = 0.813). The survival rate of patients who underwent breast conserving surgery (BCS) has recently gotten better than that of mastectomy (HR of mastectomy vs. BCS; P1 = 0.957, p = 0.790; P2 = 0.542, p < 0.001; P3 = 0.543, p < 0.001; P4 = 0.425, p < 0.001). CONCLUSIONS: The clinical factors related to the changes in breast cancer survival have improved and increased patient OS over the past 20 years in Korea. In addition, we provided new insights into the effects of age and surgery methods on prognosis in each period.

The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer.

BACKGROUND: Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. METHODS: Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.

Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients Before Neoadjuvant Chemotherapy: A Preliminary Study.

BACKGROUND: The aim of this study was to determine the feasibility of image-guided marker-clip placement in axillary lymph nodes (ALNs) for breast cancer upon initial presentation and to assess the reliability of this method with sentinel lymph node biopsy (SLNB) for axillary restaging after neoadjuvant chemotherapy (NAC). METHODS: Between June 2015 and August 2016, a marker clip was placed at a clinically positive ALN under ultrasonography (US) guidance before initiation of NAC in 20 patients. Preoperative localization of marker-clipped LNs was performed, and the localized LNs were removed by SLNB. We compared the postoperative results of the marker-clipped LNs, SLNs and ALNs. RESULTS: Image-guided marker-clip placements and localization of marker-clipped LNs were performed successfully in 20 patients. A total of 24 marker clips were inserted, and 23 marker-clipped LNs were successfully retrieved during surgery (identification rate, 23/24, 95.8%). In the 11 patients with pathologically confirmed metastatic marker-clipped LNs, four became negative after NAC, and seven maintained metastatic residues on the marker-clipped LNs. Three of the seven patients had metastatic residues on the ALNs, and two of the three patients also had negative SLNs. Marker-clipped nodes accurately predicted the axillary nodal status in these two patients compared with SLNs alone. CONCLUSION: Image-guided marker-clip placement on positive ALNs before NAC and removal with SLNB is technically feasible. This technique can improve the accuracy of the residual disease evaluation on the axilla, especially in patients with negative SLNB results, and can identify candidates for limited axillary surgery after NAC.

Expression of epithelial-mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer.

Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

High Ki67/BCL2 index is associated with worse outcome in early stage breast cancer.

AIMS: Breast cancers are heterogeneous, making it essential to recognise several biomarkers for cancer outcome predictions. Ki67 proliferation index and B cell lymphoma 2 (BCL2) proteins are widely used as prognostic indicators in many types of malignancies. While Ki67 is a marker of normal or tumour cell proliferation, BCL2 plays a central role in antiproliferative activities. A combination of these two biomarkers with contrary purposes can provide enhanced prognostic accuracy than an analysis using a single biomarker. METHODS: We evaluated Ki67 and BCL2 expression with 203 cases of breast cancer. The relative expression of each biomarker named as Ki67/BCL2 index was divided into two groups (low vs high) with the use of area under receiver operating characteristic curves. RESULTS: There were significant correlations between Ki67/BCL2 index and clinicopathological findings such as age, tumour stage, size and necrosis, histological grade, extensive intraductal component, lymphatic and vascular invasion, oestrogen receptor, progesterone receptor, human epithelial growth factor receptor 2 and p53 expression (all p<0.05). In univariate and multivariate analyses, high Ki67/BCL2 index correlated with shorter disease-free survival and overall survival in patients with early stage invasive ductal carcinoma (all p<0.05). CONCLUSIONS: The Ki67/BCL2 index should be considered as a prognostic predictor in patients with early stage invasive ductal carcinoma.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).

BACKGROUND: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. METHODS/DESIGN: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. DISCUSSION: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01589367.

Diagnostic and prognostic relevance of MMP-11 expression in the stromal fibroblast-like cells adjacent to invasive ductal carcinoma of the breast.

BACKGROUND: Matrix metalloproteinase 11 (MMP-11) is a matrix degrading enzyme known to be involved in the remodeling of extracellular matrix proteins. This enzyme recently has been reported to play a key role in tumor progression and results in poor clinical outcomes for several different types of tumors. METHODS: A total of 192 patients diagnosed with invasive ductal carcinoma between 2000 and 2005 were included in this study. MMP-11 expression in tumors and stromal fibroblast-like cells was analyzed by immunohistochemical staining on a tissue microarray. Subsequently, evaluation of the associations between MMP-11 expression and clinicopathological characteristics was performed. RESULTS: MMP-11 expression of stromal fibroblast-like cells was correlated with prognostic factors, including tumor size, metastasis, histological grade, central tumor fibrosis, p53 expression, and luminal A subtype and was linked to therapeutic markers, such as ER and HER2 (all p < 0.05). There was a significant relationship between worse overall survival and MMP-11 expression in both tumors and stromal fibroblast-like cells (all p < 0.05). In multivariate analysis, MMP-11 expression of stromal fibroblast-like cells was still significantly associated with poor prognosis (p = 0.043). CONCLUSIONS: MMP-11 expression was significantly related to clinicopathological parameters, which may be essential to the prediction of disease outcome in patients with invasive ductal carcinoma of the breast.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

E2F1 expression predicts outcome in Korean women who undergo surgery for breast carcinoma.

BACKGROUND: The transcriptional factors E2F1 and E2F2 have been reported to be associated with improved chemosensitivity in various cancers. We aimed to investigate whether E2F1 and E2F2 can be used as predictors of chemosensitivity in hormone-receptor-negative breast cancers (HRNBCs), which are common in Korean women. METHODS: A total of 183 patients with primary breast cancer who had undergone surgical resection were evaluated on the basis of hormonal status, age, histological subtype and grade, tumor size, lymph node metastasis, and stage. The immunohistochemical expressions of E2F1 and E2F2 were analyzed for these histopathological data and patient survival. RESULTS: E2F1 expression was associated with low histological grade (grade 1) and larger tumor size (>2 cm), while E2F2 expression was correlated only with large tumor size (>2 cm). The E2F1-positive group had less tumor recurrences, lymph node metastases during follow-up, and distant metastases than the E2F1-negative group; E2F1 expression was found to be an independent predictive factor of more favorable survival among HRNBC patients on univariate and multivariate analyses, but E2F2 expression was not. CONCLUSIONS: E2F1 may be a potential prognostic and predictive factor for clinical outcome and therapeutic results following adjuvant chemotherapy in HRNBC patients.

Menopausal Transition, Body Mass Index, and Prevalence of Mammographic Dense Breasts in Middle-Aged Women.

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35-65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend < 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96-1.00) in early transition, 0.89 (0.86-0.92) in late transition, and 0.55 (0.52-0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87-0.98), 0.83 (0.77-0.90) and 0.36 (0.31-0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women.

Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors.

The aim of the present study was to compare the efficiency of tissue microarray (TMA) results using immunohistochemistry markers applied to a variety of core sizes and full sections of gastrointestinal stromal tumors (GIST) using performance measures such as core loss rate and concordance rate. Six primary antibody markers (c-Kit, CD34, smooth muscle actin (SMA), S-100, p53, and Ki-67) were used with the TMA technique to analyze 0.6 mm, 2 mm, and 3 mm punch cores of GIST samples from 67 patients. No statistical association was found between core size and loss rate (P= 0.512). TMA results for the 0.6 mm, 2 mm, and 3 mm core showed that all core sizes could statistically significantly reflect full sections with regard to c-Kit, SMA, and S-100 antibodies, but that the 3 mm core section was the most representative except for CD34. With regard to p53 and Ki-67 staining, the 0.6 mm core section was not representative, but the 2 mm and 3 mm core sections could statistically significantly represent full section results. Among them, the 3 mm core section was more accurate than the 2 mm core section. Use of a single 3 mm core size in TMA is suitable for evaluating large numbers of protein and nuclear stains with regard to immunohistochemistry for GIST.

Different prognostic values of individual hematologic parameters in papillary thyroid cancer due to age-related changes in immunity.

PURPOSE: Several studies have reported the plausible association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of papillary thyroid cancer (PTC), but the results are inconsistent. In PTC, chronic inflammation is closely related to tumor progression, and the age of the patient has a great influence on prognosis. Therefore, considering the changes in the immune system with aging, we classified the patients according to age and assessed the prognostic value of individual hematologic parameters. METHODS: This retrospective analysis included 1,921 patients who underwent thyroidectomy for PTC. Patients were divided into 2 groups based on their age: Y-group (age < 45) and O-group (age ≥ 45). Blood counts were measured within 14 days before surgery. RESULTS: The Y-group consisted of 914 patients aged < 45 years and the O-group consisted of 932 patients aged ≥ 45. In both groups, the common prognostic factors related to disease recurrence were only 6 or more metastatic lymph node and grossly extrathyroidal extension, and hematologic parameters were different between the 2 groups. High Platelet-lymphocyte ratio (PLR) in the Y-group and high NLR in the O-group were identified as independent predictors of disease recurrence (NLR: hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.23-8.73; P = 0.018; PLR: HR, 3.08; 95% CI, 1.26-7.52; P = 0.014). CONCLUSION: The results suggest that changes in immunity with aging may affect prognosis in patients with PTC, and thus hematologic parameters might be employed as prognostic markers depending on the age of the patients.

Contrast enhanced digital mammography versus magnetic resonance imaging for accurate measurement of the size of breast cancer.

OBJECTIVE: To compare the accuracy of contrast-enhanced digital mammography (CEDM) and MRI, including maximal intensity projection (MIP) images, for measuring the tumour size of breast cancer. METHODS: We included 52 females (mean age, 50.9 years) with surgery due to breast cancer, and measured maximum diameter of main mass on mediolateral oblique (MLO) and craniocaudal (CC) views of mammography and CEDM; sagittal, axial MIP images, and early dynamic contrast-enhanced MRI (CEMRI) before surgery. Bland-Altman plot, intraclass correlation coefficient, and univariate linear regression analysis were used to evaluate the maximum size between imaging and pathology including only invasive component (OPinvasive) or with carcinoma in situ (OPmax). RESULTS: Mean OPinvasive was 15.5 mm, and overestimation rate was similar or higher than underestimation rate on all images except CC view of mammography and axial MIP image of CEDM. Mean OPmax was 21.7 mm, and underestimation rate was higher than the overestimation rate. All parameters of CEDM and CEMRI showed good agreement ( k > 0.75) with OPinvasive, with the most favourable result being the CC view of CEDM and axial MIP image of CEMRI. CONCLUSION: All views of CEDM and MRI provided accurate measurements of tumour size. Axial plane CEDM and MRI would be the first choice for image review and treatment planning, with the highest accuracy obtained by using CC view of CEDM. ADVANCES IN KNOWLEDGE: Previous studies have not compared the measurement of the tumour size using detailed sequences; in our study, we discovered that CEDM can be an alternative modality to CEMRI.