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 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.
    Cancer/Radiothérapie 04/2015; DOI:10.1016/j.canrad.2015.01.003 · 1.41 Impact Factor
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    • "<0.001 Table 3 The TCP outcome of patients with a median 10 year follow-up in the EBCTCG dataset [17] and the EORTC dataset [15]. (BCS = Breast Conserving Therapy, RT = Radiation Therapy, CI = Confidence Interval). "
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    ABSTRACT: Age is an important prognostic marker of patient outcome after breast conserving therapy; however, it is not clear how age affects the outcome. This study aimed to explore the relationship between age with the cell quantity and the radiosensitivity of microscopic disease (MSD) in relation to treatment outcome. We employed a treatment simulation framework which contains mathematic models for describing the load and spread of MSD based on a retrospective cohort of breast pathology specimens, a surgery simulation model for estimating the remaining MSD quantity and a tumor control probability model for predicting the risk of local recurrence following radiotherapy. The average MSD cell quantities around the primary tumor in younger (age⩽50years) and older patients were estimated at 1.9∗10(8)cells and 8.4∗10(7)cells, respectively (P<0.01). Following surgical simulation, these numbers decreased to 2.0∗10(7)cells and 1.3∗10(7)cells (P<0.01). Younger patients had smaller average surgical resection volume (118.9cm(3)) than older patients (162.9cm(3), P<0.01) but larger estimated radiosensitivity of MSD cells (0.111Gy(-1) versus 0.071Gy(-1), P<0.01). The higher local recurrence rate in younger patients could be explained by larger clonogenic microscopic disease cell quantity, even though the microscopic disease cells were found to be more radiosensitive. Copyright © 2015. Published by Elsevier Ireland Ltd.
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    • "While these figures are quite striking, it has to be taken into account that at the time these studies were performed, adjuvant systemic therapy was less often used and was less effective together with less optimal surgery compared to the present time. Unfortunately, these studies did not distinguish between true recurrences and second primary breast cancers [2]). "
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    ABSTRACT: Occurrence of breast cancer is a well-known long-term side effect of ionizing radiation (both diagnostic and therapeutic). The radiation-induced breast cancer risk increases with longer follow-up, higher radiation dose and younger age of exposure. The risk for breast cancer following irradiation for lymphomas is well known. Although data regarding the carcinogenic risk of adjuvant radiotherapy for a primary breast cancer are sparse, an increased risk is suggested with longer follow-up mainly when exposed at younger age. Particularly, patients with a BRCA1/2 mutation might be more sensitive for the deleterious effects of ionizing radiation due to an impaired capacity of repairing double strand DNA breaks. This might have consequences for the use of mammography in breast cancer screening, as well as the choice between breast conserving therapy including radiotherapy and mastectomy at primary breast cancer diagnosis in young BRCA1/2 mutation carriers. Good data regarding this topic, however, are scarce, mainly due to constraints in the design of performed studies. In this review, we will discuss the current literature on the association between ionizing radiation and developing breast cancer, with particular attention to patients with a BRCA1/2 mutation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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