Myoepithelial carcinoma of the breast treated with surgery and chemotherapy.

Myoepithelial carcinoma (malignant myoepithelioma) of the breast is a rare tumor, for which only a limited number of reports have been published. Most of the reports emphasized diagnosis and pathology but not biological behavior and treatment. We report a 61-year-old patient with breast myoepithelial carcinoma who developed locoregional and distant metastases and received many chemotherapy regimens. She presented with an elastic hard mass of the left breast. Breast conserving surgery was performed as part of both diagnosis and treatment. From the results of histological and immunohistochemical examinations, this case was considered to be a myoepithelial carcinoma. Fifteen months after the completion of adjuvant radiotherapy, distant metastasis of the left parasternal lymph node metastasis developed. She was treated by further excision and received a total of four regimens of chemotherapy including a combination of doxorubicin and cyclophosphamide. She received chemotherapy for 20 months after the diagnosis of metastasis.

miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer.

Recent analyses have identified heterogeneity in estrogen receptor α (ERα)-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis, are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissue were compared between ER(high) Ki67(low) tumors and ER(low) Ki67(high) tumors by miRNA and mRNA microarrays. Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs in these groups. We identified a downregulation of miR-1290 in ER(high) Ki67(low) tumors. Among 11 miRNAs that were upregulated in ER(high) Ki67(low) tumors, quantitative RT-PCR detection analysis using 64 samples of frozen breast cancer tissue identified six miRNAs (let-7a, miR-15a, miR-26a, miR-34a, miR-193b, and miR-342-3p). We picked up 11 genes that were potential target genes of the selected miRNAs and that were differentially expressed in ER(high) Ki67(low) tumors and ER(low) Ki67(high) tumors. Protein expression patterns of the selected target genes were analyzed in 256 ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its putative targets, BCL2, FOXA1, MAPT, and NAT1, were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased expression of NAT1 and FOXA1. Our results suggest that miR-1290 and its potential targets might be associated with characteristics of ER-positive breast cancer.

High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients.

OBJECTIVE: MicroRNAs have emerged as a new class of non-coding genes involved in regulating cell proliferation, differentiation and viability. Recent studies have identified miR-210 as one of a set of hypoxia-regulated microRNAs and demonstrated a direct regulatory role of HIF-1 alpha for its transcription. Here, we assessed miR-210 expression in Japanese triple-negative breast cancers and determined its clinical significance. METHODS: TaqMan MicroRNA assays for miR-210 expression were performed on 161 samples of Japanese breast cancer tissue (58 triple-negative breast cancer and 103 estrogen receptor positive/HER2 negative). Correlations between miR-210 expression and clinicopathological factors were analyzed. The effects of several variables on survival were tested by a Cox proportional hazards regression analysis. RESULTS: miR-210 expression in triple-negative breast cancers was significantly higher than in estrogen receptor-positive/HER2-negative breast cancers (P < 0.001). Patients whose triple-negative breast cancers showed low miR-210 expression experienced significantly better disease-free and overall survival than those with high miR-210 expression (P = 0.02 and P = 0.05, respectively). Although the prognosis of patients with triple-negative breast cancers is poor, Cox univariate and multivariate analyses demonstrated that a higher expression of miR-210 was an independent factor indicating a worse prognosis than for patients with a low level of miR-210. CONCLUSIONS: The degree of miR-210 expression might be a clinically useful prognostic factor for decision-making regarding treatment in the adjuvant setting, especially in node-negative triple-negative breast cancer patients.

Genetic and environmental predictors, endogenous hormones and growth factors, and risk of estrogen receptor-positive breast cancer in Japanese women.

The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We have recently shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive subtype. It is necessary to establish risk factors capable of predicting the risk of ER-positive breast cancer that will enable the efficient selection of candidates for preventive therapy. We analyzed genetic factors, including 14 single nucleotide polymorphisms (SNPs), environmental risk factors (body mass index, age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake, and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 [IGF1] and IGF binding protein 3 [IGFBP3]), and mammographic density in 913 women with breast cancer and 278 disease-free controls. To identify important risk factors, risk prediction models for ER-positive breast cancer in both pre- and postmenopausal women were created by logistic regression analysis. In premenopausal women, one SNP (CYP19A1-rs10046), age, pregnancy, breastfeeding, alcohol intake, serum levels of prolactin, testosterone, and IGFBP3 were considered to be risk predictors. In postmenopausal women, one SNP (TP53-rs1042522), age, body mass index, age at menopause, serum levels of testosterone, and IGF1 were identified as risk predictors. Risk factors may differ between women of different menopausal status, and inclusion of common genetic variants and serum hormone measurements as well as environmental factors might improve risk assessment models. Further validation studies will clarify appropriate risk groups for preventive therapy.

Distinct expressions of microRNAs that directly target estrogen receptor α in human breast cancer.

Estrogen receptor (ER) α is essential for estrogen-dependent growth, and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ERα-positive breast cancer. Breast cancer patients show a wide range of ERα expression levels and the levels of expression in individual patients change during disease progression and in response to systemic therapies. However, little is known about how the expression of ERα in human breast cancer is regulated. Recently, several microRNAs (miRNAs) that directly target ERα have been identified, and we previously demonstrated that miR-206 expression was downregulated in ERα-positive human breast cancer. In this study, expression levels of miRNAs that directly target ERα, including miR-18a, miR-18b, miR-22, miR-193b, miR-221/222 and miR-302c, were analyzed in human breast cancer samples by quantitative reverse transcription-PCR analysis. Correlations between the expression levels of these miRNAs and clinicopathological factors, including prognosis, were analyzed. miR-18a expression was much higher in ERα-negative than in ERα-positive tumors (P < 0.0001), with the expression levels of miR-18a not differing in ERα-positive breast cancer as a function of ERα protein level. Surprisingly, the expression levels of miR-193b and miR-221 were significantly lower in ERα-negative than in ERα-positive tumors (P = 0.0015 and P = 0.0045, respectively), and the levels of these miRNAs gradually increased as ERα protein expression increased. There was no statistically significant association between miR-22 and ERα expression, and miR-302c expression was minimal in human breast cancer samples. Prognostic analysis showed that low miR-18b expression was significantly associated with improved survival in HER2-negative breast cancer, although miR-18b expression was not correlated with ERα protein expression. Our results suggest that miRNAs that directly target ERα have distinct roles in not only regulating ERα but also regulating other target genes in human breast cancer.

High estrogen receptor expression and low Ki67 expression are associated with improved time to progression during first-line endocrine therapy with aromatase inhibitors in breast cancer.

BACKGROUND: Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)-positive breast cancer in postmenopausal women. However, many breast cancer patients with tumors expressing ER are unresponsive to aromatase inhibitors, and all patients with advanced disease eventually develop resistance to the therapy. METHODS: Twenty-one postmenopausal women with Stage II to IV breast cancer were treated with aromatase inhibitors as first-line endocrine therapy without surgery. Expression levels of ER, progesterone receptor, HER2 and Ki67 were examined by immunohistochemistry, and correlations between response and duration of the therapy and these levels were analyzed. RESULTS: Patients whose tumors contained two thirds or more ER-positive cells effectively responded to aromatase inhibitors (P = 0.006) and displayed longer time to progression during first-line endocrine therapy (P = 0.003) and longer time to endocrine therapy failure (P = 0.02). Patients whose tumors showed less than 15% Ki67 labeling index also displayed longer time to progression (P = 0.003). CONCLUSION: High ER expression and low Ki67 expression were associated with improved time to progression with aromatase inhibitors as first-line endocrine therapy. Our findings will be helpful when endocrine therapy is planned in either early stage or advanced breast cancer.