woman lymph armpit examination. Node-Positive Breast Cancer
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Patients with node-positive breast cancer that becomes node-negative after neoadjuvant chemotherapy can omit regional nodal irradiation (RNI) without increasing their risk for recurrence, suggests data presented at the 2023 San Antonio Breast Cancer Symposium.

The de-escalation of treatment could spare a large proportion of patients the side effects associated with RNI including an increased risk for radiation dermatitis, chest wall pain/tenderness, pneumonitis, lymphedema, cardiac disease, and late secondary malignancies, as well as an increased risk for post-reconstruction complications in patients who undergo breast reconstruction after mastectomy.

Presenting author Eleftherios Mamounas, MD, chair of the NRG Oncology Breast Committee, professor of surgery at the University of Central Florida, and medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute, tells Inside Precision Medicine that “the rates of converting positive lymph nodes to negative with neoadjuvant chemotherapy have historically increased considerably with the development of more active neoadjuvant chemotherapy regimens.”

“For patients with triple-negative breast cancer, the conversion rate is about 60–65% with neoadjuvant chemotherapy plus immunotherapy. It is around 50% for hormone receptor-positive/HER2-positive patients and reaches about 80% in those with hormone receptor-negative/HER2-positive tumors when treated with neoadjuvant chemotherapy plus dual anti-HER2 therapy. For hormone receptor-positive/HER2-negative tumors the rate of conversion is lower (around 20-25%) with neoadjuvant chemotherapy,” he explains.

However, at present there is no established standard of care for how patients whose nodal status changes should be treated after surgery.

“There is an active debate on whether these patients should be treated as patients with lymph node-positive disease (which is how they were diagnosed) or as patients with lymph node-negative disease (which is how they present at the time of surgery),” says Mamounas.

If treated as patients with lymph node-positive disease, they would be recommended to undergo chest wall irradiation plus RNI after mastectomy or whole breast irradiation plus RNI after breast-conserving surgery. Alternatively, if their disease were considered lymph node-negative, they would be eligible to omit regional nodal irradiation after surgery.

To address this, Mamounas and colleagues conducted the NRG Oncology/NSABP B-51/RTOG 1304 phase III clinical trial, which included 1,556 patients (median age 52 years, 31% non-White) with lymph-node positive, non-metastatic breast cancer who underwent at least eight weeks of neoadjuvant chemotherapy and were node-negative after mastectomy or breast-conserving surgery.

The participants were randomly assigned in equal proportions to undergo chest wall irradiation plus RNI after mastectomy or whole breast irradiation plus RNI after breast-conserving surgery (RNI arm) or to observation after mastectomy or whole breast irradiation after breast-conserving surgery (no-RNI arm).

After a median five years of follow-up, there were 50 invasive breast cancer recurrences in the RNI arm and 59 in no-RNI arm. The difference between the two groups was not statistically significant and corresponded to five-year recurrence-free rates of 92.7% with RNI and 91.8% without regional nodal irradiation.

Distant recurrence and overall survival rates were also similar between the arms, with 93.4% of patients in each arm free from distant recurrence five years after surgery, and 93.6% of those in the RNI arm and 94.0% of those in the no RNI arm alive at five years.

The findings could help improve precision medicine for people with node-positive breast cancer.

“One of the main premises with the use of neoadjuvant chemotherapy is that by monitoring tumor response to the neoadjuvant chemotherapy regimen, loco-regional therapy (surgery or radiation) and adjuvant systemic therapy can be further tailored compared to what would have been if surgery took place upfront,” said Mamounas.

“Several studies have shown that the extent of surgery can be tailored based on tumor response to neoadjuvant chemotherapy (such as conversion of inoperable tumors to operable, conversion of mastectomy candidates to candidates for breast conserving surgery).

“Our study shows that with neoadjuvant chemotherapy, we can also tailor the use of adjuvant radiotherapy based on nodal response to the neoadjuvant chemotherapy regimen.”

A potential limitation of the study is that patients have so far experienced fewer breast cancer recurrences than expected, which impacted the researchers’ ability to perform the planned statistical analyses based on the number of recurrences. However, the statistical plan of the study also stipulated analyses 10 years after the initiation of the study, which was reached in 2023. The researchers will now carry out a longer follow-up to strengthen their analysis.

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