Internal Mammary Lymph Node Radiation Safe Over the Long Term

M. Alexander Otto, MMS, PA

August 05, 2021

A new report is reassuring regarding the long-term cardiopulmonary safety of internal mammary lymph node irradiation after breast cancer surgery.

After a median follow-up 15.7 years among almost 4000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the "absolute rates and differences" of heart and lung complications "were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques," say investigators.

The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, in Antwerp, Belgium.

The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.

Women in the trial were treated from 1996 to 2004. "We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to non-target tissues," the team says.

In the end, "our findings...have important ― reassuring ― consequences for decision-making concerning elective lymph node treatment in breast cancer," the researchers comment.

The study was published online on July 28 in the Journal of the National Cancer Institute.

Resolving the Debate

There's been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, Ohio, in an accompanying editorial.

Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.

White says the new EORTC trial "moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation."

She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes "should generally be treated" as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she writes.

Mostly Grade 1 Morbidity

Women in the study had stage I–III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.

The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.

The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, vs 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, vs 1.1%.

The incidence of any cardiac disease was 11.1% in the radiation arm, vs 9.4% in the control group.

Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation vs 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.

The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.

Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.

Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.

Still, "it seems logical to take the pre-existing cardiac co-morbidity of patients into consideration," the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.

The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and White have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online July 28, 2021. Abstract, Editorial

M. Alexander Otto is a physician assistant with a master's degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email:

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