Forgoing radiotherapy possible for select postmenopausal women with early breast cancer

For postmenopausal women with genomically defined low-risk stage I breast cancer who have been initiated on endocrine therapy immediately after breast-conserving surgery, the risk of recurrence is low despite the omission of radiation therapy, as shown in the IDEA* trial.

At 5 years, the rate of freedom from recurrence was 99 percent (95 percent confidence interval [CI], 96–100). One of the two recurrences recorded was an isolated axillary event at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an ipsilateral breast event at 49 months treated with repeat breast-conserving surgery. [SABCS 2023, abstract GS02-08]

Recurrence beyond 5 years occurred in six additional patients, including five with ipsilateral breast events and one with ipsilateral breast event plus regional recurrence.

“No distant recurrences were observed. So that’s reassuring,” noted lead study investigator Dr Reshma Jagsi of Emory University in Atlanta, Georgia, US.

“It’s also important to note that most of our patients were compliant with endocrine therapy,” including both of the patients who experienced recurrences within 5 years and half of those who had recurrences after 5 years,” Jagsi added.

Crude rates of ipsilateral breast event overall were 3.3 percent among patients in the 50–59-year age group and 3.6 percent among those in the 60–69-year age group. The respective crude rates of overall relapse were 5.0 percent and 3.6 percent.

Overall and breast cancer-specific survival rates at 5 years were both 100 percent, with two deaths documented later than 5 years.

“Long-term follow-up of this trial and [other similar studies such as PRECISION, PRIMETIME and EXPERT, among others] will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend,” Jagsi said. “Such 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.”

Toning down the enthusiasm

IDEA included 200 postmenopausal patients between 50 and 69 years of age (mean 63 years) with pT1N0 hormone receptor-positive, HER2-negative breast cancer with Oncotype DX 21-gene recurrence score of ≤18 (mean 11). All patients underwent lumpectomy with negative margins of ≥2 mm and consented to 5 years of endocrine therapy and 10 years of surveillance on study but no radiation treatment. The median follow-up was 5.21 years.

At baseline, tumours were grade 1 in 85 patients, grade 2 in 109, and grade 3 in six. The mean tumour size was 10 mm. Lymphovascular invasion was present in 16 tumours and an extensive intraductal component in 11.

While IDEA offers compelling evidence for omitting radiotherapy in certain cases, Jagsi called for a balanced interpretation of the data. 

For the most part, the findings should not be generalized to patients who have less extensive surgery than the pathologic nodal evaluation and margin requirements of the study, she said. “Caution is necessary if compliance with endocrine therapy is not expected, given that compliance was high in this sample of women who enrolled on trial.”

Also important is to recognize that advances in radiation therapy have substantially reduced toxicity and short-term burden of treatment since IDEA was initiated, with implications for a favourable risk-benefit ratio especially among women with long life expectancies, Jagsi pointed out. As such, IDEA should not be framed as a way to avoid “something really horrible.”

“The worst thing we can do for our patients is make them think radiation is the danger radiation sign and something worth avoiding because it is harsh, and toxic, and brutal, and awful. There are many patients who benefit meaningfully from radiation treatment,” Jagsi said.

“So, we don’t want to go too far in overstating the interest in omitting radiation therapy, but 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,” she added.

*Individualized Decisions for Endocrine therapy Alone