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Which High-Risk Breast Cancers for Lymph Node Irradiation?

Goodwin, Peter M.

doi: 10.1097/01.COT.0000558225.74979.cb
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VIENNA—Oncologists should consider adding regional lymph node (LN) irradiation to breast-conserving therapy and whole breast irradiation for subgroups of patients with high-risk early breast cancer, according to a leading European oncologist who reviewed priorities in radiation therapy at the 2019 St. Gallen International Breast Cancer Conference.

Philip Poortmans, MD, PhD, Head of Radiation Oncology at the Institut Curie in Paris and President of the European CanCer Organisation, told Oncology Times that two key factors were emerging that made the issue of regional irradiation more pertinent.

“We see a de-escalation of axillary surgery, which is in part compensated by more regional irradiation, and we have the outcomes of three major trials: the Canadian one, the EORTC one, and the Danish one,” he noted.

All three of the recent studies demonstrated that elective LN irradiation improved disease-free survival. And the Danish study had also found an increase in overall survival (OS).

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Canadian Data

The Canadian study of 1,832 women with node-positive or high-risk node-negative breast cancer found no significant difference in the primary endpoint of OS—after 10 years follow-up—between patients who had LN irradiation added to whole breast radiation and those treated with whole breast irradiation alone. OS was 82.8 percent in the nodal-irradiation group and 81.8 percent in the control group.

But there was a difference in breast cancer recurrence. Disease-free survival was 82.0 percent in the nodal-irradiation group compared with 77.0 percent in the control group. Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis and lymphedema.

The study concluded that “the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival, but reduced the rate of breast-cancer recurrence.” (N Engl J Med 2015;373:307-316)

Poortmans said that 2 years since the data were published clarity had still not emerged to identify which patients benefited most from LN irradiation.

“On the one hand, we have the evidence that regional irradiation improves outcomes and we also have surgeons [doing] less surgery. So we are more tempted to irradiate those patients to the lymph nodes,” he said.

But the question had become: Which patients benefited in terms of disease-free and overall survival? Poortmans said it was important to know in which patients such additional radiation could be avoided. “It's not a treatment that we have to apply bluntly to all patients.”

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EORTC & Danish Trials

Fifteen-year results from the EORTC study showed a “significant reduction of breast cancer mortality and breast cancer recurrence” by internal mammary and medial supraclavicular lymph node irradiation in stage I-III breast cancer. But the study found this had not been converted into improved OS. There was no a clear explanation for this (J Clin Oncol 2018;36(15_suppl):504).

The Danish study with 3,089 patients investigated whether irradiation of the internal mammary lymph nodes improved survival in patients with early-stage breast cancer (J Clin Oncol 2016;34(4):314-320). Possible survival benefit might have been offset by radiation-induced heart disease, so the researchers assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer to test this hypothesis.

Two natural cohorts were available for investigation thanks to the clinical practice of giving additional radiation patients only to patients in whom exposure of the heart could more easily be avoided. Those who had cancer in the right breast were allocated to receive IMNI while those with left-sided disease did not.

Eight-year overall survival rates were 75.9 percent with IMNI versus 72.2 percent without IMNI. Breast cancer mortality was 20.9 percent with IMNI versus 23.4 percent without any LD irradiation. The risk of distant recurrence at 8 years was 27.4 percent with IMNI versus 29.7 percent. The conclusion was that “IMNI increased overall survival in patients with early-stage node-positive breast cancer.”

Poortmans regarded data from the three studies collectively as evidence that LN irradiation was a benefit in high-risk disease. But he said more clarity was needed to define subgroups of patients who stood to benefit the most.

“We [need] data on clinical, tumor, and patient-related characteristics.” He regretted that only retrospective data were available on tumor biology, and he awaited upcoming results from the ongoing trials among biologically selected patients to see where regional LN irradiation could help or can be avoided.

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Real-World Clinical Decisions

“I would apply regional lymph node irradiation for the high-risk patients—especially patients with more lymph nodes involved in the axilla, with a tumor located medially in the breast (compared to laterally), [with] larger tumors (more than 3 cm), more aggressive tumor types (like triple-negative, luminal B types, or patients with loco-regionally advanced disease)—especially those who reacted very well to primary systemic therapy,” explained Poortmans. But he didn't expect any benefit in patients with early-stage luminal A subtypes.

When asked how big the potential gains were from adding LN irradiation to the treatment of appropriate patients, he estimated improvements of around 3 percent in disease-free survival and around 2.5 percent for OS. But he noted that was for all patients grouped together.

“If you select patients better, the benefits will be larger. Also, it's not about all or nothing. Most of those patients have radiation to the breast or to the chest wall anyway—so [LN irradiation is] adding an extra volume.”

Peter M. Goodwin is a contributing writer.

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
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