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SAN ANTONIO -- Postmenopausal women with genomically low-risk early hormone receptor (HR)-positive breast cancer had a low risk of recurrence with endocrine therapy alone after lumpectomy, a randomized trial showed.

The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 100% without adjuvant radiation therapy (RT) in 186 women ages 50-69 followed for at least 56 months. The 5-year freedom from any recurrence was 99%.

Two patients had recurrences before 5 years, but an additional six patients had later recurrences, although no patient had distant (metastatic) recurrence. Though promising, the results do not mean that women with low-risk HR-positive breast cancer should routinely omit radiation therapy, said Reshma Jagsi, MD, of Emory University and Winship Cancer Institute in Atlanta, during the San Antonio Breast Cancer Symposium (SABCS).

"These findings shouldn't be generalized to patients who have less extensive surgery [than required in the clinical trial] or who are expected not to be compliant with endocrine therapy," she said. "The other cautionary note is perhaps even more important to reflect on. Advances in radiation therapy have substantially reduced the toxicity and short-term burden of treatment, even since the initiation of this trial in 2015. The patients eligible for [this trial] can also receive radiation treatment in five fractions or less."

"The worst thing we can do for our patients is make them think radiation is the 'Danger. Radiation' sign because it is harsh and toxic and brutal and awful," Jagsi continued. "There are many patients who benefit meaningfully from radiation treatment. We don't want to go too far in overstating the interest in omitting radiation therapy. Of course, we know that some women do wish to avoid the burden and potential toxicity of radiation therapy altogether, even though it is lower than it once was."

The results were published simultaneously in the

Unresolved Issues

Similar favorable results with radiotherapy omission came from the LUMINA trial, albeit in a somewhat different patient population, said SABCS invited discussant Andrea Barrio, MD, of Memorial Sloan Kettering Cancer Center in New York City. Both studies sought to determine whether tumor biology can be used to identify patients who might omit radiotherapy, as it has for systemic therapy. Collectively the two studies suggest that "radiotherapy would have a negligible effect in further lowering the risk of local recurrence."

Differences in the trials' enrollment criteria and patient populations raised several unresolved issues, said Barrio. What is the ideal surgical margin width? Should lobular and high-grade cancers be included? Should lymphovascular invasion and extensive intraductal component be allowed? What is the preferred assay for determining risk?

"In thinking about application into real-world practice, it is hard enough to convince people to stop irradiating women over 70, but I do hope that we will try to convince some patients or practitioners that we don't need to irradiate everyone over 50," said Barrio. "Over 50% of women over 70 receive RT, despite evidence supporting omission. This may be due to endocrine therapy adherence. Over 30% of women discontinue endocrine therapy. That's not what they saw in these trials, but that's what we see in the real world."

A landmark trial showed that radiation therapy could be safely omitted with reasonable local control in selected patients 70 or older. A published at the same time failed to show a similar positive outcome in women 50 or older. Subsequent long-term follow-up showed that RT could be omitted with reasonable 10-year recurrence rates in selected patients and .

IDEA Trial

Jagsi reported 5-year findings from the single-arm , involving 200 women ages 50-69 with stage I unicentric HR-positive/HER2-negative breast cancer treated with lumpectomy and 5 years of adjuvant endocrine therapy. All of the patients had an Oncotype DX Recurrence Score (RS) ≤18, indicating a low risk of recurrence. Data analysis was performed 5 years after the last enrolled patient underwent lumpectomy.

The study population had a mean age of 62, mean tumor size of 10 mm, and mean RS of 11. All of the patients were pathologically node negative. Histology was ductal in 85% and lobular in 10%. Grade distribution was grade 1 in 42.5%, grade 2 in 54.5%, and grade 3 in 3%. Lymphovascular invasion was present in 14.5% of cases.

Crude rates of ipsilateral breast events (IBE) for the entire follow-up period were 3.3% (two of 60) among patients ages 50-59 and 3.6% (five of 140) for patients ages 60-69. Crude rates of overall recurrence were 5.0% (three of 60) for patients 50-59 and 3.6% (five of 140) for patients 60-69. Seven of the eight recurrences that occurred over the entire follow-up period were IBEs, and one patient had an IBE with regional recurrence.

Overall, 169 of 200 patients remained compliant with endocrine therapy (received as prescribed 90% of the time), including both patients who recurred before 5 years and three of the six patients who recurred after 5 years, said Jagsi.

Four ongoing randomized trials should provide definitive answers about omitting RT in early breast cancer. One trial involves patients 50 or older, one involves patients 60 or older, one involves patients 70 or older, and the fourth has a study population ≥50 to <70.

"Long-term follow-up of this trial and others are essential to help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend," said Jagsi. "These efforts strive to empower patients with choices and return to them a sense of agency that can be deeply meaningful in the context of a recent cancer diagnosis, which every single person in this room knows takes away a sense of control."

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