Prescription Refill Gap of Endocrine Treatment from Electronic Medical Records as a Prognostic Factor in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Discontinuation of hormone therapy is known to lead to a poorer prognosis in breast cancer patients. We aimed to investigate the prescription gap as a prompt index of medication adherence by using prescription data extracted from patient electronic medical records. METHODS: A total of 5,928 patients diagnosed with invasive, non-metastatic breast cancer, who underwent surgery from January 1, 1997 to December 31, 2009, were enrolled retrospectively. The prescription data for 4.5 years of hormonal treatment and breast cancer-related events after treatment completion were analyzed. We examined the characteristics and prognoses of breast cancer in patients with and without a 4-week gap. RESULTS: Patients with a gap showed a significantly higher risk of breast cancer recurrence, distant metastasis, breast cancer-specific death, and overall death after adjustment (hazard ratio [HR], 1.389; 95% confidence interval [CI], 1.089–1.772; HR, 1.568; 95% CI, 1.158–2.123; HR, 2.108; 95% CI, 1.298–3.423; and HR, 2.102; 95% CI, 1.456–3.034, respectively). When patients were categorized based on gap summation, the lower third (160 days) and fourth (391 days) quartiles showed a significantly higher risk of distant metastasis (HR, 1.758; 95% CI, 1.186–2.606 and HR, 1.844; 95% CI, 1.262–2.693, respectively). CONCLUSION: A gap of > 4 weeks in hormonal treatment has negative effects on breast cancer prognosis, and can hence be used as a sentinel index of higher risk due to treatment non-adherence. Further evaluation is needed to determine whether the gap can be used as a universal index for monitoring the adherence to hormonal treatment.

Marked Individual Variation in Isoflavone Metabolism After a Soy Challenge Can Modulate the Skeletal Effect of Isoflavones in Premenopausal Women

Soy-isoflavones may act as estrogenic agonists or antagonists depending on the endogenous hormone status. These clinical effects can be exerted variably in individuals by the metabolic ability to produce a more potent metabolite than precursors. The objective of this randomized, double-blind, placebo-controlled study was to investigate the skeletal effect of isoflavones according to their metabolic variability in premenopausal women. Volunteers were randomly assigned to receive either soy-extract isoflavones (n=32) or lactose (n=21) once a day for three menstrual cycles. After intervention, the urinary excretions of isoflavones and their metabolites were significantly higher in the soy group than in the placebo group and showed a large inter-individual variation. Women in the soy group were divided into subgroups according to their ability to excrete more potent metabolites. Serum osteocalcin and urine deoxypyridinoline showed a tendency to increase after a challenge in equol high-excretors. Serum osteocalcin concentration in the genistein high-excretors increased significantly after a challenge (P=0.04) but did not increase in either the placebo or genistein low-excretors. An estrogenic antagonistic effect of isoflavones on bone turnover was observed in premenopausal women who are able to produce more potent metabolites.

Terapia médica de la ginecomastia con tamoxifeno. Influencia del volumen y duración de la ginecomastia en el resultado terapéutico / Influence of size and duration of gynecomastia on its response to treatment with tamoxifen

Background. Gynecomastia is treated when it is painful, there are psychosocial repercussions or it does not revert in less tan two years. It is treated with the antiestrogenic drug tamoxifen, but there are doubts about its effectiveness in high volume gynecomastias or in those lasting more than two years. Aim. To assess the effectiveness and safety of tamoxifen for gynecomastia and the influence of its volume and duration on the response to treatment. Patients and methods. Forty three patients with gynecomastia, aged 12 to 62 years, were studied. Twenty seven patients had a pubertal physiological gynecomastia, in eight it was caused by medications, in four it was secondary to hypogonadism, in three it was idiopathic and in one it was due to toxic exposure. Twenty patients had mastodynia and in 33, gynecomastia had a diameter over 4 cm. It lasted less than two years in 30 patients, more than two years in nine and four did not recall its duration. All were treated with tamoxifen 20 mg/dayfor 6 months. A follow up evaluation was performed at three and six months of treatment. Results. Mastodynia disappeared in all patients at three months. At six months gynecomastia disappeared in 26 patients (62 percent), but relapsed in 27 percent. All gynecomastias caused by drugs with antiandrogen activity disappeared. Fifty two percent of gynecomastias over 4 cm and 90 percent of those of less than 4 cm in diameter disappeared (p<0.05). Fifty six percent of gynecomastias lasting more than two years and 70 percent of those of a shorter duration disappeared (p=NS). Two patients had diarrhea or flushes associated to the therapy. Conclusions: Tamoxifen is safe and effective for the treatment of gynecomastia. Larger lesions have a lower response to treatment.

Effect of estradiol benzoate on the heat shock protein 70, 90 expressions in endometrial glandular epithelial cell / 中华妇产科杂志

Objective To explore the effect of estradiol benzoate on the expressions of heat shock protein (HSP)70, 90 in endometrial glandular epithelial cell. Methods Normal endometrial glandular epithelial cells were isolated, and cultured by enzymolysis method and identified by electron microscopy and immunohistochemical analysis. The normal endometrial glandular epithelial cells were treated with culture medium only, estradiol benzoate (10 -9 , 10 -8 , 10 -7 or 10 -6 mol/L), estradiol benzoate(10 -9 , 10 -8 , 10 -7 or 10 -6 mol/L) and antiestrogen ICI 182780(fulvestrant,faslodex, 1?mol/L)and ICI 182780 only for 6, 12, 18, 24 hours respectively. The dose-and time-related effect of estradiol benzoate and ICI 182780 on the cell growth was measured by mononuclear cell direct cytotoxicity assay (methyl thiazolyl tetrazolium assay), and that on the expression of HSP70 and HSP90 in normal endometrial glandular epithelial cell in vitro was measured by immunohistochemical analysis and computerized image analysis system. Results Estradiol benzoate stimulated cell growth in a time-and dose-dependent manner and the effect was attenuated by the antiestrogen ICI 182780. The average cell growth rates of 10 -9 , 10 -8 , 10 -7 , 10 -6 mol/L estradiol benzoate for 24 hours were(170?9)%,(207?11)%,(231?12)%,(257?10)%, which were significantly higher than those of 6 hours (117?13)%, (129?10)%, (146?10)%, (176?6)%, P