Concurrent hormone and radiation therapy in patients with breast cancer: what is the rationale?

Endocrine therapy is often given together with postoperative radiotherapy in patients with breast cancer and positive hormone-receptor status. However, few experimental or clinical studies address the combined effects of hormone and radiation therapy. Preclinical models have shown changes in tumour cell kinetics with the addition of tamoxifen, and some show reduced tumour cell death with concurrent anti-oestrogen treatment and radiotherapy. Although data from in-vitro studies support the notion of antagonistic effects of concurrent tamoxifen and radiotherapy on tumour cells, in-vivo research suggests a synergistic effect that could be attributable to micro-environmental changes in tumour responsiveness to ionising radiation and hormone therapy. Retrospective studies suggest that in practical application, concurrent administration of tamoxifen with radiotherapy does not compromise local control but might increase toxicity. Preliminary results from simultaneous treatment with aromatase inhibitors and radiation indicate that this combination of endocrine and radiation therapy could enhance cytotoxicity and improve tumour response. Further studies are needed to clarify the physiological mechanisms activated by oestrogens, which will allow a more thorough understanding of the complex interactions between 17beta-oestradiol and P53/P21WAF1/CIP1/Rb pathways and of the interaction between endocrine therapy and radiotherapy. © 2009 Elsevier Ltd. All rights reserved.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Interaction between the Kansas City Cardiomyopathy Questionnaire and the Pocock’s clinical score in predicting heart failure outcomes

Purpose: Heart failure (HF) is a complex syndrome. Its appropriate management should combine several health measurements. We assessed the relationship between the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Pocock’s clinical score. // Methods: We conducted a prospective registry of HF outpatients. The main outcome was occurrence of death or hospitalization during a 6-month follow-up. A multivariate logistic regression was performed, including the KCCQ overall summary score, the Pocock’s clinical score and their interaction in the model. // Results : From January 2008 to December 2010, 143 patients were involved. Mean age of patients was 68 years, and 74 % were men. KCCQ’s overall summary score and Pocock’s clinical score were inversely correlated (r = −0.24, p = 0.026). A total of 61 (42.7 %) events occurred. There was a high proportion of events (77.8 %) in patients with a Pocock’s clinical score >50 %, whatever the KCCQ score value. When the KCCQ score was ≤50 %, there was a low increase in risk as the Pocock’s clinical score increased (OR 2.0 [0.6; 6.6]). However, when the KCCQ score was between 50 and 75 or ≥75 %, there was a high increase in risk as the Pocock’s clinical score increased (OR 6.9 [1.2; 38.9] and OR 7.4 [0.8; 69.7], respectively). // Conclusions : Patients with a high Pocock’s clinical score are at a high risk of death or hospitalization. For patients with a low Pocock’s clinical score, the KCCQ score can identify those at risk of these events

Une nouvelle ère pour la radiothérapie avec des avancées prometteuses = A new area for radiotherapy with favourable features

Radiotherapy is a complex medical speciality involving technology research, biology research and clinical research. All these basic researches are performed in order to optimise the management of cancer treatment patients. The aim of the present review is to present radiotherapy as a moving speciality whatever the concerned section. It will be particularly described the new approaches in terms of technology but also clinical developments.English AbstractJournal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Estrogens decrease γ-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53

Purpose: Sequential administration of radiotherapy and endocrine therapy is considered to be a standard adjuvant treatment of breast cancer. Recent clinical reports suggest that radiotherapy could be more efficient in association with endocrine therapy. The aim of this study was to evaluate the estrogen effects on irradiated breast cancer cells (IR-cells). Methods and Materials: Using functional genomic analysis, we examined the effects of 17-β-estradiol (E2, a natural estrogen) on MCF-7 breast cancer cells. Results: Our results showed that E2 sustained the growth of IR-cells. Specifically, estrogens prevented cell cycle blockade induced by γ-rays, and no modification of apoptotic rate was detected. In IR-cells we observed the induction of genes involved in premature senescence and cell cycle progression and investigated the effects of E2 on the p53/p21waf1/cip1/Rb pathways. We found that E2 did not affect p53 activation but it decreased cyclin E binding to p21waf1/cip1 and sustained downstream Rb hyperphosphorylation by functional inactivation of p21waf1/cip1. We suggest that Rb inactivation could decrease senescence and allow cell cycle progression in IR-cells. Conclusion: These results may help to elucidate the molecular mechanism underlying the maintenance of breast cancer cell growth by E2 after irradiation-induced damage. They also offer clinicians a rational basis for the sequential administration of ionizing radiation and endocrine therapies. © 2007 Elsevier Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe