Zhang Qingyuan

Immoderate inhibition of estrogen by anastrozole enhances the severity of experimental polyarthritis.

Aromatase inhibitors have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. Meanwhile, more and more breast cancer patients who are treated with aromatase inhibitors as adjuvant therapies often experience arthralgias and musculoskeletal aching, in some cases, have necessitated discontinuation of treatment. We therefore use a rat model of human RA to test the hypothesis that anastrozole, an aromatase inhibitor, could enhance arthritis. The parameters used for analyzing the disease severity included paw volume, radiology, histopathological examination, markers for cytokine profile, immunophenotypic assays, and immune response to type II collagen. Administration of anastrozole significantly increased the severity of arthritis. Anastrozole induced the increased levels of proinflammatory cytokines, IFN-gamma, IL-12, and the decreased levels of IL-4, IL-10 secretion. We further found that anastrozole suppressed the differentiation of naive T cells to Treg cells, and it blocked the balance of IgG2a/IgG1 in peripheral blood. Meanwhile, estradiol concentration was the lowest in the anastrozole group. In a well-established model of postmenopausal RA, anastrozole potently promote the progression of arthritis and the associated development of osteoporosis. This potential problem should alert the oncologists and other health professionals.Aromatase inhibitors have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. Meanwhile, more and more breast cancer patients who are treated with aromatase inhibitors as adjuvant therapies often experience arthralgias and musculoskeletal aching, in some cases, have necessitated discontinuation of treatment. We therefore use a rat model of human RA to test the hypothesis that anastrozole, an aromatase inhibitor, could enhance arthritis. The parameters used for analyzing the disease severity included paw volume, radiology, histopathological examination, markers for cytokine profile, immunophenotypic assays, and immune response to type II collagen. Administration of anastrozole significantly increased the severity of arthritis. Anastrozole induced the increased levels of proinflammatory cytokines, IFN-gamma, IL-12, and the decreased levels of IL-4, IL-10 secretion. We further found that anastrozole suppressed the differentiation of naive T cells to Treg cells, and it blocked the balance of IgG2a/IgG1 in peripheral blood. Meanwhile, estradiol concentration was the lowest in the anastrozole group. In a well-established model of postmenopausal RA, anastrozole potently promote the progression of arthritis and the associated development of osteoporosis. This potential problem should alert the oncologists and other health professionals.

Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment

OBJECTIVE Androgen receptor (AR) plays an important role in male breast cancer (MBC). Additionally, endocrine therapy is the most important treatment in oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to investigate the role of AR in MBC treatment and prognosis and to analyse the relationship between AR and the effect of tamoxifen treatment in MBC patients. METHODS AR protein levels and other tumour characteristics (e.g. expression of ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue from 102 MBC patients were determined using immunohistochemical analysis. Additionally, the relationship between AR status and clinicopathological features was analysed using the χ(2)-test. Association with survival was initially analysed using the Kaplan-Meier method and the log-rank test, and Cox regression analysis was used to adjust for other prognostic indicators. RESULTS High expression of AR was not correlated with T-stage, histological grade, HER2 status and the status of other sex hormone receptors, but was associated with lymph node metastases (P=0.032). AR-positive patients showed significantly shorter 5-year overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS) rates (P=0.026) than AR-negative patients. By contrast, for patients who received tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate than AR-positive patients (P=0.025). Additionally, the median TTP and OS were significantly different (P=0.02 for TTP; P=0.029 for OS). CONCLUSIONS AR expression correlates strongly with both OS and DFS in patients with MBC. AR-positive patients can predict a poorer clinical outcome than AR-negative patients after adjuvant tamoxifen therapy.

Expression of HOXD3 correlates with shorter survival in patients with invasive breast cancer

Hox genes encode a family of homeodomain-containing transcription factors that determine cellular identity during development and which are also expressed in some types of cancer. The HOXD3 gene, a member of the Hox gene family, has been demonstrated to be expressed in several tumor cell lines, which exhibit enhanced invasion and metastasis through coordinate expression of metastasis-associated factors. However, the clinical impact of HOXD3 in breast cancer remains unclear. In the current study, we examined the expression of HOXD3 and integrin β3 by immunohistochemical staining in patients with invasive breast cancer. We found that HOXD3 expression was significantly frequent in high histopathological grade and hormone-receptor negative breast cancer patients. The expression of HOXD3 was closely associated with integrin β3 expression. Furthermore, patients with high HOXD3 expression levels in their breast tumors had significantly shorter survival times than patients in which HOXD3 was weakly expressed in breast tumors. Univariate and multivariate analyses confirmed that increased HOXD3-expression was an independent and significant factor in predicting poor prognosis for patients with breast cancer. In conclusion, HOXD3 expression is a significant unfavorable prognostic factor for patients with invasive breast cancer and as such is a potentially useful prognostic marker for breast cancer.