Search Results
Search for other papers by W R Miller in
Google Scholar
PubMed
Search for other papers by Glorianne Lazaro in
Google Scholar
PubMed
Search for other papers by Chris Smith in
Google Scholar
PubMed
Search for other papers by Lindy Goddard in
Google Scholar
PubMed
Search for other papers by Nicola Jordan in
Google Scholar
PubMed
Search for other papers by Richard McClelland in
Google Scholar
PubMed
Search for other papers by Peter Barrett-Lee in
Google Scholar
PubMed
Search for other papers by Robert I Nicholson in
Google Scholar
PubMed
Search for other papers by Stephen Hiscox in
Google Scholar
PubMed
Introduction Molecular and biological profiling has identified a subset of oestrogen receptor-positive (ER+) luminal breast cancers that co-expresses the epidermal growth factor receptor 2 (ERBB2/‘HER2’) protein ( Guiu et al . 2012 ). HER2
Department of Biostatistics, School of Public Health and Key Lab of Health Technology Assessment, National Health and Family Planning Commission of the People’s Republic of China, Fudan University, Shanghai, People’s Republic of China
Search for other papers by Minlu Zhang in
Google Scholar
PubMed
Search for other papers by Peng Peng in
Google Scholar
PubMed
Search for other papers by Kai Gu in
Google Scholar
PubMed
Search for other papers by Hui Cai in
Google Scholar
PubMed
Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai, People’s Republic of China
Search for other papers by Guoyou Qin in
Google Scholar
PubMed
Search for other papers by Xiao Ou Shu in
Google Scholar
PubMed
Search for other papers by Pingping Bao in
Google Scholar
PubMed
node status ( Arriagada et al . 2006 ), clinical stage ( Zahl & Tretli 1997 , Natarajan et al . 2009 ), oestrogen receptor (ER) status ( Hess et al . 2003 , Dignam et al . 2009 ) and molecular subtypes ( Mulligan et al . 2008 , O’Brien et al
Department of Pharmacy, Tongren hospital affiliated to Wuhan University (the third hospital of Wuhan), Wuhan, China
Search for other papers by Xiong Wang in
Google Scholar
PubMed
Search for other papers by Li Ma in
Google Scholar
PubMed
Search for other papers by Qiao-yan Ding in
Google Scholar
PubMed
Search for other papers by Wen-yu Zhang in
Google Scholar
PubMed
Search for other papers by Yong-gang Chen in
Google Scholar
PubMed
Search for other papers by Jin-hu Wu in
Google Scholar
PubMed
Search for other papers by Hong-feng Zhang in
Google Scholar
PubMed
Search for other papers by Xiu-li Guo in
Google Scholar
PubMed
Institute, Beijing, China. Prolactinoma animal models Oestrogen-treated rats and intragastric administration The oestrogen-treated rat is a well-known model of pituitary lactotroph hyperplasia and hyperprolactinaemia ( Heaney et al. 1999 ). The
Search for other papers by J Marsden in
Google Scholar
PubMed
Search for other papers by N P M Sacks in
Google Scholar
PubMed
Search for other papers by M P Schrey in
Google Scholar
PubMed
Search for other papers by K V Patel in
Google Scholar
PubMed
Search for other papers by T J Powles in
Google Scholar
PubMed
Search for other papers by J Chang in
Google Scholar
PubMed
Search for other papers by W R Miller in
Google Scholar
PubMed
Both mammary adipose tissue and breast cancers have the ability to aromatize androgens into oestrogens. Such potential may maintain the growth of hormone-dependent tumours. It has therefore been important to determine the effects of new aromatase inhibitors such as formestane, exemestane, anastrozole and letrozole on oestrogen biosynthesis and concentrations of endogenous hormones within the breast. Studies based on in vitro incubations of breast cancer and cultures of mammary adipose tissue fibroblasts demonstrate that these drugs are highly effective inhibitors, with IC50 values ranging between 1 and 50 nM (although the relative efficacy varies between tissues and test systems). Despite this potential, in vitro incubations of breast tissues from patients treated with type II inhibitors such as aminoglutethimide and letrozole can display paradoxically high aromatase activity; this appears to be caused by the reversible nature of the inhibition, coupled with induction/stabilization of the aromatase enzyme. To assess in situ effects within the breast, postmenopausal women with large primary breast cancers have been treated neoadjuvantly with aromatase inhibitors using a protocol that included (i) breast biopsy before treatment, (ii) definitive surgery after 3 months of treatment and (iii) infusion of [3H]androstenedione and [14C]oestrone in the 18 h immediately before biopsy and surgery. With this study design, it has been shown that drugs such as letrozole profoundly inhibit in situ aromatase activity and reduce endogenous oestrogens within the breast.
Search for other papers by A O Mueck in
Google Scholar
PubMed
Search for other papers by H Seeger in
Google Scholar
PubMed
Endometrial carcinoma is listed under the absolute contraindications to hormone therapy (HT). According to current opinion, HT after stage I or II is still considered an option, and continuous combined oestrogen/progestogen replacement therapy (CCEPT) would be recommended. However, up to now, only observational studies have been put forward. Although none of these studies have established an increased rate of recurrence or mortality, alternatives such as phytopreparations and tibolone, or particular psychotherapeutic drugs, such as venlafaxine, should be considered for the relief of climacteric complaints. Progestogen-only therapy (PT) particularly has been considered. However, the currently discussed possible progestogen effects regarding an increased risk of breast cancer have to be taken into account. Indeed, the wider discussion about the gestagen effects regarding the risk of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches or gels) instead of CCEPT, and this is also now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinoma, such as hypertension, obesity, polycystic ovary syndrome (PCO) and diabetes mellitus. However, each form of HT should be only exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.
Search for other papers by C Ferlini in
Google Scholar
PubMed
Search for other papers by M Di Stefano in
Google Scholar
PubMed
Search for other papers by M Marone in
Google Scholar
PubMed
Search for other papers by C Gaggini in
Google Scholar
PubMed
Search for other papers by G Ferrandina in
Google Scholar
PubMed
Search for other papers by A Riva in
Google Scholar
PubMed
Search for other papers by E Bombardelli in
Google Scholar
PubMed
Search for other papers by A De Pasqua in
Google Scholar
PubMed
Search for other papers by S Mancuso in
Google Scholar
PubMed
Search for other papers by G Scambia in
Google Scholar
PubMed
Abstract
Docetaxel is a semi-synthetic drug that has been shown to be effective in refractory advanced breast cancer. Its main mechanism of action seems to be to block microtubule depolymerisation. In this study we investigated the interaction between docetaxel and the pure anti-oestrogen ICI 182,780 on different oestrogen receptor-negative cancer cells, some of which express the classical multi-drug resistance (MDR) phenotype. ICI 182,780 potentiated the anti-proliferative effect of docetaxel only in the MDR-positive cells. Isobolic analysis demonstrated that this chemosensitising effect was a synergism. In the same conditions where synergism was detected, cell cycle analysis demonstrated an augmentation of cells blocked at the G2/M phase of the cell cycle, suggesting that ICI 182,780 increases the activity of docetaxel. In order to test this hypothesis, we performed bcl-2 western blot analysis and demonstrated that the addition of ICI 182,780 to docetaxel induced bcl-2 phosphorylation only in MDR-positive cells. The functional inactivation of bcl-2 is probably responsible for the commitment to apoptosis, since the combined docetaxel/ICI 182,780 treatment was able to foster a massive apoptosis in MDR-bearing cells as demonstrated by morphological analysis.
Our results suggest that the synergism between docetaxel and ICI 182,870 is due to a block in P-glycoprotein activity, thus determining cell cycle block, bcl-2 inactivation and apoptosis induced by docetaxel accumulation.
