Correspondence

1846 www.thelancet.com Vol 384 November 22, 2014

Findings from the meta-analysis by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)1 seem to have settled the debate about the role of postmastectomy radiotherapy in patients with low axillary nodal burden. In this study,1 patients with breast cancer with one to three positive nodes were reported to benefit from postmastectomy radiotherapy in terms of locoregional recurrence, overall recurrence, and disease-specifi c mortality.

However, after 20 years, radio-therapy was not associated with improved overall survival; a survival gain from breast cancer of 7·9% only translated into a non-significant 3% gain in overall survival.1 This fi nding continues to suggest that in patients with a low nodal burden, other causes of death, particularly cardiovascular mortality, might counteract the gains of breast cancer survival conferred by radiotherapy.2 Loss of these gains is problematic in populations with a high prevalence of risks for cardiovascular disease, such as in southeast Asia,3,4 and in resource-restricted settings with low technologically advanced facilities for radiation (heart–lung sparing treatment). In these settings, the balance between the benefits and harms of radiotherapy in terms of overall survival could be tipped to the opposite direction.

In the era of personalised medicine, indications for adjuvant treatment should not only be based on cancer-specific characteristics, but also should take into account the cardiovascular risk profile of patients and the heart–lung sparing capabilities of treatment with radiation. Development of rules for clinical predictions incorporating breast cancer-specific factors5 and cardiovascular risk profiles, ethnic origin, and radiation techniques could be the way forward in prediction of the absolute overall survival gains conferred by adjuvant radiotherapy.We declare no competing interests.

*Nirmala Bhoo-Pathy, Jean-Philippe Pignol, Helena M Verkooijenovenjjay@gmail.com

Julius Centre University of Malaya, Faculty of Medicine, 50603 Kuala Lumpur, Malaysia (NB-P); Department of Radiation Oncology, Erasmus MC Cancer Institute, Netherlands (J-PP); and Imaging Division, University Medical Center Utrecht, Utrecht, Netherlands (HMV)

1 EBCTCG (Early Breast Cancer Trialists’ Collaborative Group). Eff ect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 2014; 383: 2127–35.

2 Harris EER, Correa C, Hwang W, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol 2006; 24: 4100–06.

3 Reid CM, Yan B, Wan Ahmad WA, et al. The Asia Pacifi c Evaluation of Cardiovascular Therapies (ASPECT) collaboration—improving the quality of cardiovascular care in the Asia Pacifi c Region. Int J Cardiol 2014; 172: 72–75.

4 Selvarajah S, Haniff J, Kaur G, et al. Clustering of cardiovascular risk factors in a middle-income country: a call for urgency. Eur J Prev Cardiol 2013; 20: 368–75.

5 Mukesh MB, Duke S, Parashar D, Wishart G, Coles CE, Wilson C. The Cambridge post-mastectomy radiotherapy (C-PMRT) index: a practical tool for patient selection. Radiother Oncol 2014; 110: 461–66.

Authors’ replyOur meta-analysis1 of individual patient data from trials in women given mastectomy and axillary clearance to at least level ll showed that radiotherapy reduced mortality from breast cancer by 20% in women with one to three positive lymph nodes (rate ratio [RR], irradiated vs not, 0·80, 95% CI 0·67–0·95; 2p=0·01) and by 13% in women with at least four positive lymph nodes (RR 0·87, 95% CI 0·77–0·99; 2p=0·04). Little reason of how radiotherapy works exists to think that this treatment for breast cancer has any appreciable abscopal effect and so, as Ismail Jatoi suggests, these results1 showed that a proportion of the deaths avoided by radiotherapy would have arisen from cells localised within the areas targeted by radiotherapy (ie, the chest wall and, for most trials, the regional lymph nodes).

We agree with Rajni Sethi and colleagues that doctors who use these results1 in clinical practice need to take

account of the low absolute risk of recurrence in women being considered for postmastectomy radiotherapy today compared with the women who participated in these trials. However, the proportional reductions in risk that we noted could reasonably be applied to women today who have between one and three positive nodes if they have appreciable risk of recurrence. We also agree with Nirmala Bhoo-Pathy and colleagues that clinical prediction rules incorporating both breast cancer-specifi c and other factors might be helpful in the future.

We noted that in any node positive disease, about one death due to breast cancer was avoided in the 20 years after radiotherapy for every 1·5 breast cancer recurrences of any type (ie, locoregional or distant) avoided during the fi rst 10 years. This results differs from our estimate of one death due to breast cancer avoided by 15 years for every four recurrences avoided in the first 10 years in the trials of radiotherapy after breast-conserving surgery.2 However, the women with node positive disease in the trials of postmastectomy radiotherapy generally had more advanced cancers and more extensive radiotherapy than did the women in the trials of radiotherapy after breast-conserving surgery.

Information about recurrence available for analysis in these trials is the time to first recurrence and whether that recurrence was locoregional or distant in the patient. This availability of such information enables estimations to be made of the size of the effect of radiotherapy on breast cancer recurrence of any type (ie, locoregional or distant) of cancer. However, women who are at a high risk of locoregional recurrence (eg, because they have more aggressive cancers) are also at an increased risk of distant recurrence, so rates of locoregional and distant recurrence are correlated, and additional analyses cannot remove this correlation. Radiotherapy substantially reduces the rate of local