Modern regional node radiotherapy techniques have improved survival in women with early breast cancer, an analysis spanning four decades by the early Breast Cancer Trialists’ Collaborative Group shows.
The research involving 16 randomised controlled trials and over 14,000 women showed a significant survival benefit with new, more tailored radiotherapy strategies involving local lymph nodes compared to older techniques, which largely did not involve irradiation of the chest wall in patients with node-positive disease.
The findings can be used by clinicians and patients to estimate survival gains from regional node radiotherapy as part of the shared decision-making process, according to the paper published in The Lancet.
The team analysed patient data from all randomised trials of regional lymph node radiotherapy (n=12,167 patients; 1989-2008) versus no regional lymph node radiotherapy (2,157; 1961-1978) in women with early breast cancer.
In the eight newer trials, regional node radiotherapy significantly reduced disease recurrence (rate ratio 0.88, 95% CI 0·81-0·95; p=0·0008), according to the paper published in The Lancet.
Radiotherapy also significantly reduced breast cancer mortality (RR 0.87, 95% CI 0.80-0.94; p=0·0010), and as there was no significant impact on non-breast-cancer mortality (0.97; p=0.63), all-cause mortality was also significantly reduced (0.90, 0.84-0.96; p=0.0022), a finding that the researchers said was reassuring given concerns around mammary node radiation therapy and cardiotoxicity.
Estimated absolute reductions in 15-year breast cancer mortality were 1.6% for women without positive axillary nodes, 2.7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes, the investigators reported.
Conversely, regional node radiotherapy “had little effect” on breast cancer mortality (RR 1.04, 95% CI 0.91-1.20; p=0.55) in the older trials, while non-breast-cancer mortality (1.42; p=0.00023) and all-cause mortality (1.17; p=0·0067) were significantly increased.
Radiotherapy has become more targeted over time
“Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s,” the researchers said.
They noted two key differences between the older and newer trials. For one, breast cancer regional node radiotherapy techniques have “substantially improved”, particularly during the 1980s and 1990s when radiotherapy delivery was directed by cross-sectional images, which significantly reduced incidental radiation doses to surrounding tissues.
Also, the majority (75%) of older trials included in the meta-analysis did not include chest wall radiotherapy following mastectomy in women with node-positive cancer, “which would be considered suboptimal today”.
In a linked editorial, Professor Mark Levine, a Medical Oncologist at McMaster University, Canada, said findings of the analysis show that “regional nodal irradiation clearly reduces breast cancer mortality and that the effect appears to be driven by internal mammary node radiation therapy”.
However, he also cautioned that due to advances in early breast cancer treatment, “it could be challenging to extrapolate the findings of the regional nodal irradiation meta-analysis to current patients…a new generation of trials is required to inform its application”.
“Current adjuvant therapy (e.g., taxanes, aromatase inhibitors, and trastuzumab) is more effective than that in the meta-analysis by Taylor and colleagues. Hence, the absolute reduction in death rate with regional nodal irradiation could be of smaller magnitude, which could affect clinical decision-making,” he added.