Abstract:
Background The role of radiotherapy after mastectomy in patients with breast cancer is a topic of heated debates. Although international consensus supports the routine use of post-mastectomy radiotherapy (PMRT) for breast tumours of more than 5 cm in diameter, or with four or more histologically involved lymph nodes, the value of PMRT among women who are at intermediate risk for loco-regional recurrence (LRR), such as patients with 1-3 involved nodes, is still unclear. Aims 1) To study the effect of radiotherapy after a mastectomy in breast cancer patients and in specific subgroups defined by demographic and tumour factors 2) To determine the factors influencing the receipt of radiotherapy after a mastectomy in breast cancer patients for whom radiotherapy was strongly indicated. Methods This is a population-based cohort study involving patients who were diagnosed with invasive breast cancer and had undergone a mastectomy in the four District Health Board regions (Auckland, Waitemata, Counties Manukau and Waikato). Eligible patients were identified from the Auckland and Waikato Breast Cancer Registers (ABCR and WBCR), and included in the study, if they were recorded in the ABCR with the date of diagnosis between 1st January, 2000 and 30th June, 2014, or if they were recorded in the WBCR with the date of diagnosis between 1st January, 1991 and 30th June, 2014. A total of 6654 patients were included in analyses for Aim I. Cox proportional hazards regression modelling was performed to compare the hazard ratios of LRR, primary study outcome, between patients who received PMRT and those who did not. Sub-group analyses were undertaken by stage, RT indication status, site of register, age, receptor status, tumour size, and the number of involved lymph nodes. Logistic regression models were then used to identify factors that could influence LRR at 10 years in patients who received PMRT and those who did not. The study also investigated the breast cancer specific mortality, and overall mortality as secondary outcomes. For Aim II, analyses were restricted to 668 patients registered from 2010 onward for whom radiotherapy is recommended by the New Zealand guidelines. Logistic regression models were used to identify demographic and tumour factors that could influence the receipt of PMRT in New Zealand. Results Analyses for Aim I indicated that PMRT reduced the risk of LRR in all groups, and sub-groups of patients. The risk of LRR at 10 years was lowest (<8%) in patients with stage I and II, with no routine indication for PMRT, aged 50-70, ER and PR both positive or the node negative particularly in those who did not receive PMRT. In patients who did not receive PMRT, age, the number of involved nodes, grade 3 tumours, lymphovascular invasion (LVI), double-negative tumours, and systemic treatment predicted LRR at 10 years whereas in patients who received PMRT, only the number of involved nodes, and double-negative tumours influenced LRR at 10 years. PMRT had little effect on overall survival, and no significant effect on breast cancer specific survival except in patients with advanced conditions of the disease (stage III or RT strongly indicated group). Analyses for Aim II revealed that 29% of patients did not receive PMRT. Almost all tumour factors predicted the receipt of PMRT but some demographic factors such as older age (80 and over), living in rural areas, and being treated in public health care facilities also predicted the lower receipt of PMRT. The associations with ethnicity were not statistically significant, but Māori and Pacific patients were less likely to receive PMRT. Conclusions Aim I: Low risks of LRR at 10 years (<8%) were seen in some patient groups, but in all these groups, the risk of LRR in PMRT patients appeared to be lower than that in non-PMRT patients. The mortality analyses suggested a small benefit for RT in breast cancer specific and in overall mortality. This result suggests that the New Zealand guidelines published in 2009 are a valid guide to best clinical practice. Aim II: 29% of patients for whom radiotherapy is recommended by the New Zealand guidelines, do not receive this treatment. Some of these variations (in terms of clinical indications) may be explicable and acceptable but significant variations in terms of demographic factors indicates the need for further efforts to understand these factors and take actions to reduce the impact.