Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trialsEarly Breast Cancer Trialists’ Collaborative Group (EBCTCG)Lancet201137817071716325425222019144

The Lancet (Impact Factor: 45.22). 11/2011; 378(9804):1707-16. DOI: 10.1016/S0140-6736(11)61629-2
Source: PubMed


After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.
We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.
Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7-17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6-6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2-17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8-5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (≥20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1-12·5), 1·1% (-2·0 to 4·2), and 0·1% (-7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5-27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8-15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.
After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.
Cancer Research UK, British Heart Foundation, and UK Medical Research Council.

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Available from: Rodrigo Arriagada, Aug 25, 2015
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    • "Radiotherapy is recommended for most patients for local control following breast conserving surgery, as well as following mastectomy in patients who are at high risk of recurrence345. However, some patients are resistant to radiotherapy and the failure of local control in breast cancer decreases the overall survival rate of patients[6,7]. Thus, identifying both a molecular signature to predict the outcome of radiotherapy and targets to sensitize radioresistant cells is essential for improving the efficacy of radiotherapy in breast cancer. "
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    ABSTRACT: Although radiotherapy resistance is associated with locoregional recurrence and distant metastasis in breast cancers, clinically relevant molecular markers and critical signaling pathways of radioresistant breast cancer are yet to be defined. Herein, we show that HER2-STAT3-survivin regulation is associated with radiotherapy resistance in HER2-positive breast cancers. Depletion of HER2 by siRNA sensitized HER2-positive breast cancer cells to irradiation by decreasing STAT3 activity and survivin, a STAT3 target gene, expression in HER2-positive breast cancer cells. Furthermore, inhibition of STAT3 activation or depletion of survivin also sensitized HER2-positive breast cancer cells to irradiation, suggesting that the HER2-STAT3-survivin axis is a key pathway in radiotherapy resistance of HER2-positive breast cancer cells. In addition, our clinical analysis demonstrated the association between HER2-positive breast cancers and radiotherapy resistance. Notably, we found that increased expression of phosphorylated STAT3, STAT3, and survivin correlated with a poor response to radiotherapy in HER2-positive breast cancer tissues. These findings suggest that the HER2-STAT3-survivin axis might serve as a predictive marker and therapeutic target to overcome radiotherapy resistance in HER2-positive breast cancers.
    Full-text · Article · Jan 2016 · Oncotarget
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    • "Les femmes âgées sont sous-traitées par tous les modes, y compris le traitement systémique (Bouchardy et al., 2007;Sostelly et al., 2013;Townsley et al., 2005). Ceci est peut-être dû à la susceptibilité perçue ou réelle à la toxicité, à la comorbidité , ainsi qu'aux croyances des médecins ou aux préférences des patientes concernant la qualité de vie et les bénéfices absolus (Bouchardy et al., 2007;Elkin et al., 2006;Ring et al., 2013)Darby et al., 2011;Peto et al., 2012). Le premier essai clinique aléatoire effectué chez des patientes de 65 ans et plus atteintes d'un cancer du sein au stade précoce a montré que les patientes traitées par capécitabine présentaient des probabilités de rechute deux fois supérieures (RR : 2,09, 95 %; IC : 1,38-3,17; p < 0,001), et présentaient presque deux fois plus de risques de mourir (RR : 1,85, 95 %; IC : 1,11-3,08; P = 0,02) comparativement à celles traitées par la chimiothérapie standard (cyclophosphamide , méthrotexate et fluoroucacil[CMF]ou cyclophosphamideMuss et al., 2009). "

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    • "Radiotherapy improved survival in breast cancer after breast conservation surgery and mastectomy [1] [2] [3] [4]. However, cardiovascular disease and lung cancer mortality rates had significantly increased after radiotherapy with more than 15 years follow-up [5]. "
    F.Chi · S.Wu · J.Zhou · F.Li · J.Sun · Q Lin · H.Lin · X.Guan · Z.He
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    ABSTRACT: Purpose. - This study determined the dosimetric comparison of moderate deep inspiration breath-hold (mDIBH) using active breathing control (ABC) and free-breathing (FB) intensity-modulated radiotherapy (IMRT) after breast-conserving surgery (BCS) for left-sided breast cancer. Patients and methods. - 31 patients were enrolled. One free breathe (FB) image and two mDIBH images were obtained. A field in field (FIF) -IMRT FB plan, a FIF-IMRT mDIBH1 plan and a FIF-IMRT mDIBH2 plan were compared the dosimetry to target volume (TV) coverage of the glandular breast tissue and organs at risks (OARs) for each patient. Results. - The breath-holding time under mDIBH extended significantly after breathing training (P < 0.05). There was no significant difference between the FB mDIBH1 and mDIBH2 in the TV coverage. The volume of the ipsilateral lung in the FB were significantly smaller than the mDIBH1 and mDIBH2 (P < 0.05); however, there was no significant difference between the mDIBH1 and mDIBH2. There were no significant differences in TV coverage between the FIF-IMRT FB, FIF-IMRT mDIBH1 and FIF-IMRT mDIBH2 (all P > 0.05). The dose to ipsilateral lung, coronary artery and heart in the FIF-IMRT FB plans were significantly lower than FIF-IMRT mDIBH1 and FIF-IMRT mDIBH2 (all P < 0.05); however, there were no significant differences between the FIF-IMRT mDIBH1 and the FIF-IMRT mDIBH2. Conclusion. - The whole-breast FIF-IMRT under mDIBH with ABC after BCS in left-sided breast cancer can reduce the irradiation volume and dose to OARs. There are no significant differences between various mDIBH states in the dosimetry of irradiation to the FIF-IMRT TV coverage and OARs.
    Full-text · Article · Apr 2015 · Cancer/Radiothérapie
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