Radiotherapy targeting lymph nodes near the breastbone and collarbone cuts deaths from breast cancer over 22 years, but does not improve overall survival, a long-term trial has found.

The trial randomised 4,004 women with stage I-III breast cancer to receive internal mammary and medial supraclavicular lymph node radiotherapy (IM-MS-RT), or not, in addition to their standard treatment. All had involved axillary nodes and/or tumours located centrally or medially in the breast. The study ran across 13 European centres between 1996 and 2004, and the median patient age was 54.

After a median follow-up of 22 years, the authors, including Dr Shaymaa Hosni, a consultant clinical oncologist at Nottingham University Hospitals NHS Trust, reported in CA: A Cancer Journal for Clinicians [link here]:

• Breast cancer-specific mortality was lower with IM-MS-RT (18.6% vs 22.4%, HR 0.82, p=0.006)
• Any breast cancer recurrence was lower with IM-MS-RT (25.7% vs 28.3%, HR 0.88, p=0.0369)
• Overall survival (61.0% vs 61.8%), disease-free survival (48.2% vs 49.0%) and distant metastases-free survival (58.9% vs 59.8%) were similar between groups
• Deaths from non-breast cancer or unknown causes were higher with IM-MS-RT (20.4% vs 15.8%, HR 1.26, p=0.002)
• Cardiac disease (15.2% vs 11.7%), cardiac fibrosis (2.7% vs 1.7%) and lung fibrosis (6.3% vs 3.2%) were all more common with IM-MS-RT

The authors said the breast cancer benefit of IM-MS-RT “was maintained but… the overall results were jeopardised by increased non-breast cancer-related mortality.”

The picture changed over time. At 10 years, IM-MS-RT had improved disease-free survival, distant metastases-free survival and breast cancer mortality, with a marginal overall survival benefit. By 15 years, only breast cancer mortality and recurrence remained significantly reduced.

The authors also noted that patients who had fewer than 10 lymph nodes examined during surgery showed a borderline overall survival benefit from IM-MS-RT, although this was weaker than at the 15-year analysis. They said this raised the possibility that IM-MS-RT could be more useful for patients undergoing less extensive axillary surgery. However, they cautioned this was difficult to apply in current practice, since many node-positive patients now receive systemic therapy first, followed by tailored, less extensive surgery and radiotherapy guided by tumour response.

The authors said breast cancer recurrences and treatment-related side effects continued to occur more than two decades after diagnosis, showing the disease remained a long-term threat. They called for ongoing patient education, tailored follow-up and risk-adapted treatment, and for longer follow-up in future trials.