Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Coxankylometer nach Prof. C. Heine in Innsbruck

Ohne Zusammenfassung (Hierzu Tafel VIII.)     

PR35THE INCIDENCE OF NON‐MELANOMA SKIN CANCER IN NEW ZEALAND

Background It is estimated that skin cancers cost $33 million per annum to the New Zealand healthcare system. Basal cell carcinoma and squamous cell carcinoma are the commonest types of non melanoma skin cancers (NMSCs). Anecdotal evidence indicates that there has been a doubling in the incidence of NMSCs in New Zealand over the last decade. Because of the high incidence mandatory reporting of NMSCs to the National Cancer Registry is not required. This lack of accurate data has led to poor health care policies and strategies including funding and workforce planning. Aims The aims of this study are to (1) present the latest statistics on NMSCs in New Zealand, including the incidence across different regions over the last decade, patient demographics, anatomic distribution of NMSCs, incidence and sites of metastasis, and disease‐specific survival; to (2) the histopathology of NMSCs, including surgical margins, histologic grade, and perineural, lymphatic, and vascular invasion; and (3) the relative role of different faculties treating NMSCs. Method This project has been approved by the multi‐centre ethics committee. A retrospective review was conducted from patients’ histology records from public and private pathology laboratories within defined catchment areas. Criterion for analysis is a confirmed diagnosis of NMSC treated surgically. A Microsoft Access database is created that will facilitate subsequent data retrieval and analysis. Results and Conclusion It is hoped that this up‐to‐date data will form the framework for the development of sound and sustainable healthcare policies of management of NMSCs including management strategies and workforce planning, and research direction on this common disease.     

Orbital hydatid cysts: Report of four cases

Hydatid cysts of central nervous system are rare and comprise only 2% to 3% of all hydatid cysts reported. Orbital localization is very uncommon and has been reported less than 1 % of all hydatid diseases. The primary treatment of hydatid disease is surgical. The most important complication of the surgical treatment is secondary hydatidosis due to spillage of the cyst contents. Because of the difficulties of the orbital localization, total extirpation of the cysts without rupture is almost impossible. Preventing spontaneous rupture of the cysts during surgery and postoperative antihelmintic treatment should be taken into consideration in these cases.This study includes four cases who underwent surgery for orbital hydatid cysts. Radiological characteristics, operative technique and postoperative medical therapy are discussed.     

类粘蛋白的遗传表型对阿米替林血浆游离型药物浓度和蛋白结合率的影响

目的：探讨类粘蛋白(orosomucoid, ORM)表型对弱碱性药物阿米替林血浆游离浓度和蛋白结合率的影响. 方法：对28名健康受试者的去唾液酸血清ORM用等电聚焦电泳、免疫印迹法进行表型分型.ORM1的三种表型分别为纯合子ORM1 F1 (n=10)、ORM1 S (n=8)和杂合子ORM1 F1S(n=10).受试者口服单剂量的硫酸阿米替林片50 mg,测定服药后不同时间血浆阿米替林总浓度(RP-HPLC)和游离浓度(微超滤离心/RP-HPLC). 结果：给药后12和24 h,三组不同ORM1表型者阿米替林血浆总浓度的经时过程、血浆t1/2、Cmax和tmax值相似.与ORM1 S表型组比较,ORM1 F1表型组的阿米替林游离浓度较高;而蛋白结合率较低,12 h为(82.77±4.05)%,24 h为(79.99±4.39)% (P<0.01).杂合子ORM1 F1S表型组的游离药物浓度和蛋白结合率介于两组纯合子表型之间. 结论：不同ORM1表型,将明显影响弱碱性药物阿米替林的血清游离药物浓度和蛋白结合率;ORM1 F1表型者药物的血浆蛋白结合率最低,而游离型药物浓度最高.临床用药中应予以注意,并适当调整给药剂量.