PURPOSE: The purpose of this study was to investigate the non-inferiority of omitting radiotherapy (RT) after breast-conserving surgery (BCS) for hormone receptor (HR)‒positive T1N0 breast cancer in elderly women. MATERIALS AND METHODS: From 2004 to 2014, HR-positive T1N0 breast cancer patients aged 50 years or older and receiving BCS were retrieved from the Surveillance, Epidemiology, and End RESULTS: 18 database. After propensity score matching between the no-RT and RT groups, univariate and multivariate analyses were performed. Identified prognostic factors were used to stratify the risk groups. In each risk group, 10-year cancer-specific survival (CSS) rates were compared between the no-RT and RT groups. RESULTS: After propensity score matching, the numbers of patients in the no-RT and RT groups were both 18,586. For patients who satisfied both a tumor size of 1-10 mm and a tumor grade of 1-2, omitting RT did not decrease the CSS rate at any age group, ranging from ≥ 50 to ≥ 85 years; for patients aged ≥ 50 years, the 10-year CSS rates in the no-RT and RT groups were 97.2% and 96.8%, respectively (adjusted hazard ratio, 0.862; p=0.312). However, for patients with a tumor size of 11-20 mm or tumor grade of 3-4, RT significantly increased the CSS rate irrespective of age. CONCLUSION: RT after BCS for HR-positive T1N0 breast cancer in elderly women might be omitted without causing a decrease in the CSS rate, but only in patients who satisfy both a small tumor size (≤ 10 mm) and low tumor grade (1-2).
Aged ; Breast Neoplasms* ; Breast* ; Epidemiology ; Female ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Propensity Score* ; Radiotherapy ; Radiotherapy, Adjuvant* ; Receptors, Estrogen ; Receptors, Progesterone

PURPOSE: In breast cancer, response to endocrine therapy depends on estrogen receptor and progesterone receptor status. However, poor prognosis is conferred on patients with hormone receptor (HR)-positive breast cancer. We aimed to examine weakly positive HR breast cancer by comparing weakly positive HR to strongly positive HR and negative HR breast cancer. METHODS: We examined the clinical and biological features of 1,496 women with breast cancer, and these patients were categorized according to HR status as weakly positive, strongly positive, and negative HR breast cancer. RESULTS: In this study, among 1,496 patients with breast cancer, negative HR breast cancer was found in 374, weakly positive HR breast cancer in 90 and strongly positive HR breast cancer in 1,032 patients. Our multivariate analysis showed that there were differences in T stage, tumor-node-metastasis stage, vascular invasion, histologic grade and type, and Ki-67 index. Patients with weakly positive HR breast cancer had an increased risk of death and recurrence compared with those with strongly positive HR breast cancer and had similar prognosis as patients with negative HR breast cancer. CONCLUSION: Patients with weakly positive HR breast cancer received endocrine therapy because they were regarded as having positive HR breast cancer. However, their prognosis of overall survival and relapse-free survival was similar to that in patients with negative HR breast cancer. Therefore, we need to closely observe and consider active treatment for patients with weakly positive breast cancer.
Breast Neoplasms ; Breast ; Estrogens ; Female ; Humans ; Multivariate Analysis ; Prognosis ; Receptors, Estrogen ; Receptors, Progesterone ; Recurrence ; Triple Negative Breast Neoplasms

PURPOSE: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. METHODS: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. RESULTS: KBCS registry data (2006–2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p < 0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p < 0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p < 0.001). CONCLUSION: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.
Breast Neoplasms* ; Breast* ; Estrogens ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Phenobarbital ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Registries ; Retrospective Studies ; Seoul ; Trastuzumab ; Treatment Outcome

Objective: To investigate the expression of the G-protein coupled estrogen receptor (GPER) in the testis of the male mouse with kidney yin or kidney yang deficiency and its influence on the reproductive function of the mouse. METHODS: We randomized 30 six-week-old male Kunming mice into three groups of equal number: kidney yang deficiency, kidney yin deficiency, and normal control, and established the models of kidney yang deficiency and kidney yin deficiency by peritoneal injection of hydrocortisone at 50 mg/kg for 5 days and 25 mg/kg for 10 days, respectively. We observed the behavioral changes of the mice using the elevated plus-maze, exhaustive swimming and field experiment, examined the semen quality with the automatic sperm quality analyzer, calculated the average number of the offspring, measured the serum testosterone (T) and estradiol (E2) levels and T/E2 ratio by Roche electrochemiluminescence assay, and determined the localization and expression of GPER in the testis by immunohistochemistry and immunofluorescence staining. RESULTS: Compared with the mice with kidney yin deficiency, those with kidney yang deficiency showed remarkably fewer entries into the open arm and central area (P <0.05) and shorter time of exhaustive swimming (P <0.05), but no statistically significant difference in the time spent in the open arm or the central area (P >0.05); the latter group also exhibited significant decreases in the epididymal sperm count (［7.27 ± 1.30］ vs ［3.05 ± 1.06］ ×108/g, P <0.01), sperm motility (［54.15 ± 13.52］ vs ［51.57 ± 8.75］ %, P <0.01) and average number of the offspring (6.46 vs 4.33, P <0.05), a slight increase in the rate of morphologically abnormal sperm (［13.42 ± 2.32］ vs ［15.39 ± 2.48］ %, P >0.05), and markedly reduced serum T (［24.96 ± 6.18］ vs ［16.72 ± 5.92］ ng/dl,P <0.05), E2 (［19.81 ± 4.01］ vs ［15.24 ± 1.11］ pg/ml,P <0.05) and T/E2 ratio (1.41 vs 1.25, P <0.05). The expression of GPER was found in the cytoplasm of the Leydig cells, negative in the nuclei and cell membrane, significantly higher in the kidney yang than in the kidney yin deficiency group (P <0.05). CONCLUSIONS The numbers of sperm and offspring decreased while the percentage of morphologically abnormal sperm increased in both the kidney yang and kidney yin deficiency mice, even more significantly in the former, which might be associated with the up-regulated expression of GPER in the testis of the mouse with kidney yang deficiency and consequently the reduced serum T level and T/E2 ratio.
Animals ; Drugs, Chinese Herbal ; Kidney Diseases ; metabolism ; Male ; Mice ; Random Allocation ; Receptors, Estrogen ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Reproduction ; physiology ; Semen Analysis ; Testis ; metabolism ; Yang Deficiency ; metabolism ; Yin Deficiency ; metabolism

Aggressive angiomyxoma is a rare mesenchymal tumor. To discuss the clinicopathological characteristics, treatment and prognosis of aggressive angiomyxoma, four cases of aggressive angiomyxoma of soft tissue in abdominopelvic cavity were collected from January 2015 to August 2017 in Peking University International Hospital. The clinical data, imaging examination, histopathological features, immunophenotype, therapy and prognosis were analysed. The related literatures were reviewed. All of the patients were adult females, age range from 27 to 49 years and mean 33 years. The clinical complaint was abdominal distention with no definite predisposing factor, or occasional physical-exam finding with no obvious discomfort. Three cases were primary and one case was recurrent. Typical layered or swirled structural sign was presented by CT and MRI scanning of three cases. All tumors located in the pelvic cavity, and attached to the uterus, vagina, rectum, bladder or ureter. One case was involved in the abdominal cavity simultaneously,adhesive to the spine, inferior vena cava and spleen. The gross appearance of tumors was from 5 to 22 cm in maximum diameter. The sectioned surfaces were soft, solid, white or yellow-gray, focally accompanied by edema, mucoid degeneration or cystic change. Microscopic observation showed that tumor cells were short spindle shaped and little atypical, the stroma was loose like edematous mucus or collagen, and the vessels were rich in thin and thick-wall. Partially the vessel wall expressed hyaline degeneration. Also tumors might infiltrate surrounding tissue, such as fat or nerve. The immunohistochemistry results of all cases were estrogen receptor and progesterone receptor diffusely moderate positive, Desmin and smooth muscle actin mostly positive, whereas CD34 expressed only in vessel and S-100 protein, CD117 and Dog1 all negative. All the tumors were complete surgical excision. During follow-up, one case recurred the second time. Our conclusions are the diagnosis of aggressive angiomyxoma is based on pathological morphology supplemented by immunohistochemistry, and the tumor may relapse after surgical resection.
Adult ; Desmin/analysis* ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Myxoma/pathology* ; Neoplasm Recurrence, Local ; Receptors, Estrogen/analysis*

PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99–7.80; p < 0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80–46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11–165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29–17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Disease Progression ; Disease-Free Survival ; Embryonic Development ; Estrogens* ; Female ; Glycoproteins ; Humans ; Multivariate Analysis ; Pregnancy ; Prognosis ; Receptors, Estrogen ; Wnt Proteins

Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3, and c-erbB-4 receptors. The investigation developed and validated quantitative reverse transcriptase polymerase chain reaction assays for each transcript to provide rapid assessment of breast cancer phenotypes for canine cancers, based on ER1, PR, and c-erbB-2/HER2 expressions, similar to those in human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expressions in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR, and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of CMT-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.
Breast Neoplasms* ; Breast* ; Cell Line ; Classification ; Epithelial Cells ; Estrogen Receptor alpha ; Estrogens* ; Humans ; Phenobarbital ; Phenotype* ; Progesterone* ; Proto-Oncogenes ; Receptors, Progesterone* ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger* ; Sequence Analysis, DNA

OBJECTIVETo explore the association of mitogen-activated protein kinase kinase-4 (MAP2K4) with the pathological features, prognosis and expression of estrogen receptor (ER) in patients with breast cancer.

METHODSThe expression of MAP2K4 was detected immunohistochemically in 102 breast cancer tissues. Chi square test was used to analyze the correlation of MAP2K4 expression with the clinicopathological features of the patients. Kaplan-Meier and log rank test were used for survival analysis of the patients. Multivariate survival analysis was performed using Cox proportional hazard regression model. The correlation between the expressionsof MAP2K4 and ER was investigated using Spearman rank correlation test.

RESULTSImmunohistochemical analysis revealed low MAP2K4 expression in 55.9%(57/102) and high MAP2K4 expression in 44.1%(45/102) of the breast cancer tissues. The expression of MAP2K4 was significantly correlated with the pathological grades of breast cancer (P=0.011). Kaplan-Meier survival analysis showed that patients with a high expression of MAP2K4 had a shorter overall survival rate than those with low MAP2K4 expressions (P=0.009). Multivariate analysis identified high expression of MAP2K4 as the independent predictor of a poor outcome of patients with breast cancer. The expressions of MAP2K4 and ER were not significantly correlated, but ER-negative patients with a high MAP2K4 expressionshowed the shortest overall survival time.

CONCLUSIONOverexpression of MAP2K4 promotes the progression in breast cancer and is associated with a poor outcome of the patients. TheER-negativepatients with a high MAP2K4 expression have the shortest overall survival time, suggestingthe value of combined examination of MAP2K4 and ER in accurate estimation of the prognosis of breast cancer patients.

Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Female ; Humans ; Kaplan-Meier Estimate ; MAP Kinase Kinase 4 ; metabolism ; Prognosis ; Proportional Hazards Models ; Receptors, Estrogen ; metabolism ; Survival Analysis

Fox transcription factors play a critical role in the regulation of a variety of biological processes. While FoxM1 behaves like the oncogenic transcription factor, FoxO3a is known as a tumor suppressor by inhibiting FoxM1. This study aimed to investigate the clinicopathological significance of FoxM1 and FoxO3a expression in breast cancer. Expression of FoxM1 and FoxO3a were analyzed by immunohistochemical staining on tissue microarray sections from 236 breast cancer patients, and correlated with various clinicopathological characteristics. Overexpression of FoxM1 correlated with adverse clinicopathological features, such as larger tumor size, lymph node metastasis, advanced tumor stage, and lymphovascular invasion. The Kaplan-Meier survival curves revealed no prognostic significance of FoxM1 expression. However, in subgroup analyses with patients of estrogen receptor (ER) positive breast cancers, FoxM1 overexpression associated with poor disease free and overall survival. No association was found between FoxO3a and FoxM1 expression. Regarding clinicopathological variables, the only association between histologic grade and FoxO3a was observed. In conclusion, FoxM1 overexpression was significantly associated with aggressive phenotypes and poor prognosis of ER-positive breast cancer. These findings suggest the possible role of FoxM1 as a prognostic biomarker and putative target of anti-cancer therapy.
Breast Neoplasms/chemistry/mortality/*pathology ; Female ; Forkhead Transcription Factors/*analysis ; Humans ; Phenotype ; Prognosis ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/*analysis

No abstract available.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/*analysis ; Biopsy ; Carcinoma, Ductal, Breast/*chemistry/*secondary/therapy ; Chemotherapy, Adjuvant ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Lymph Node Excision ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Mastectomy ; Neoadjuvant Therapy ; Neoplasm Staging ; Receptors, Estrogen/*analysis ; Skin Neoplasms/*chemistry/*secondary ; Time Factors ; Treatment Outcome ; Triple Negative Breast Neoplasms/*chemistry/*pathology/therapy