SABCS 2023: Some Patients May Safely Skip Radiation

Studies featured at this year’s San Antonio Breast Cancer Symposium (SABCS) suggest that—in some situations—adjuvant radiotherapy may not be needed.

The results could allow some patients with breast cancer to skip radiotherapy, sparing them the side effects and logistical hurdles associated with the treatment and giving them more say in how their cancer is treated.

“Although techniques of radiation treatment have improved dramatically, and it is far more efficient and tolerable now than it used to be, patients appreciate having a choice about their treatments,” noted Reshma Jagsi, MD, DPhil, who presented one of the studies. Jagsi is affiliated with the Emory University School of Medicine and the Winship Cancer Institute of Emory University.

The research presented at SABCS, which was held December 5-9, focused on three separate patient populations:

• patients with low-risk ductal carcinoma in situ (DCIS),
• postmenopausal patients aged 50-69 years with early-stage breast cancer, and
• patients whose lymph nodes became cancer-free after neoadjuvant chemotherapy.

In each study, researchers examined rates of disease recurrence and other breast cancer events in patients who skipped radiotherapy.

And in each study, they found that these rates remained quite low—suggesting that patients could forgo radiation without adversely impacting their prognosis.

“Studies like this … are important for identifying ways to improve the patient experience, both by identifying multiple treatment options to help patients regain a sense of control that a cancer diagnosis can seem to take away, and by ensuring that all patients are informed and empowered to make the decisions that are right for them,” said Jagsi.

The IDEA trial

In her presentation, Jagsi explained that patients who are diagnosed with stage 1 hormone receptor (HR)-positive breast cancer typically undergo breast-conserving surgery followed by adjuvant radiotherapy and endocrine therapy to reduce the risk of disease recurrence.

In recent years, it’s become evident that postmenopausal patients 65 years and older could opt out of adjuvant radiotherapy while maintaining a low risk of disease recurrence, but it remained unclear whether younger patients might be able to safely forgo adjuvant radiotherapy too.

Therefore, Jagsi and colleagues conducted the IDEA clinical trial, which enrolled patients between 50 and 69 years of age who had stage 1 HR-positive, HER2-negative breast cancer. The Oncotype DX Breast Recurrence Score, a laboratory test that measures gene expression in breast tumors, was used to determine each patient’s risk of disease recurrence. The results of the test are reported as a score between zero and 100, with higher scores associated with a greater likelihood of disease recurrence.

Patients with a low risk of recurrence (defined in this study as scores 18 or lower) were eligible to skip radiotherapy after breast-conserving surgery while still receiving standard-of-care adjuvant endocrine therapy for at least five years.

Among 186 evaluable patients who had skipped adjuvant radiotherapy, 100% were alive five years after surgery, and 99% (184 patients) were breast cancer-free at this time. 

“These findings indicate that younger postmenopausal patients with stage 1 breast cancer who skip radiotherapy after breast-conserving surgery have a very low risk of disease recurrence within five years,” said Jagsi.

“However, five years is an early time point for this population, and longer-term follow-up of this study and others will be essential to determine whether this option can be safely offered to women in this age group,” she added.

The E4112 trial

In another study, Seema Khan, MD, and colleagues examined the utility of adjuvant radiotherapy for patients with DCIS (a noninvasive form of breast cancer) that has a low risk of progressing to invasive cancer.

“There is an increasing realization that DCIS carries an unnecessary treatment burden for many women,” noted Khan, who is a professor at the Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

She explained that most patients with DCIS undergo breast-conserving surgery followed by adjuvant radiotherapy, which is intended to reduce the likelihood that the disease returns as DCIS or as invasive breast cancer. But whether adjuvant radiotherapy is needed for patients whose DCIS already has a low risk of returning or progressing was previously unclear.

Khan and colleagues conducted the E4112 clinical trial to assess the potential of bilateral magnetic resonance imaging (MRI) coupled with a DCIS gene expression profile to guide treatment for patients with DCIS. Previously reported results from this trial indicated that MRI could help identify patients who could opt for the less intensive breast-conserving surgery instead of a mastectomy, Khan noted.

The latest analysis aimed to determine if some of those patients who underwent breast-conserving surgery based on MRI results could also safely forgo subsequent radiotherapy based on a DCIS gene expression profile.

The analysis included 171 patients with DCIS who underwent breast-conserving surgery and whose tumor tissue was profiled using the Oncotype DX Breast DCIS Score, which, like the Oncotype DX Breast Recurrence Score, measures gene expression to predict the risk of recurrence.

In this study, patients who received a score lower than 39 were considered to have low-risk DCIS and were eligible to skip adjuvant radiotherapy, while patients with scores 39 or higher were recommended to receive adjuvant radiotherapy.

After a median follow-up of five years after surgery, 5.5% of the 75 patients with low-risk DCIS who skipped radiotherapy experienced disease recurrence, as compared with 4.8% of the 84 patients with high-risk DCIS who received radiotherapy—a difference that was not statistically significant. The findings demonstrate that patients who skipped radiation therapy did not have a greater risk of disease recurrence within five years.

“Our results indicate that the Oncotype DX Breast DCIS Score was an effective tool to stratify patients for adjuvant radiotherapy following breast-conserving surgery.” said Khan. “These findings reveal a new approach to guide treatment decisions by determining which patients may benefit from radiotherapy and which patients may safely forgo it.”

The NRG Oncology/NSABP B-51/RTOG 1304 trial

According to results shared by Eleftherios (Terry) Mamounas, MD, MPH, neoadjuvant chemotherapy may help some patients skip adjuvant regional nodal irradiation (RNI), a form of radiotherapy directed to lymph nodes near the breast. Mamounas is the chair of the NRG Oncology Breast Committee, a professor at the University of Central Florida, and medical director of the Comprehensive Breast Program at the Orlando Health Cancer Institute.

Patients who are diagnosed with breast cancer that has already spread to regional lymph nodes may receive neoadjuvant chemotherapy; in some cases, neoadjuvant therapy completely eradicates the cancer from the lymph nodes. Currently, there is no established standard of care for how these patients should be treated after surgery, Mamounas explained.

“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),” he said.

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 RNI after surgery.

To evaluate the impact of RNI on patient outcomes, Mamounas and colleagues conducted the NRG Oncology/NSABP B-51/RTOG 1304 clinical trial. The study enrolled patients diagnosed with lymph node-positive, nonmetastatic breast cancer whose lymph nodes were found to be cancer free after neoadjuvant chemotherapy and who had undergone either mastectomy or breast-conserving surgery.

Evaluable patients (1,556 patients) had similar outcomes whether they received adjuvant RNI or not: 91.8% of patients who skipped RNI and 92.7% of those who received RNI were free of invasive breast cancer recurrences five years after surgery. Distant recurrence and overall survival rates were also similar between the arms.

“Our findings suggest that downstaging cancer-positive regional lymph nodes with neoadjuvant chemotherapy can allow some patients to skip adjuvant RNI without adversely affecting oncologic outcomes. Follow-up of patients for long-term outcomes continues,” Mamounas summarized.