Investigators used low recurrence scores on a genomic assay as guidance for selection of favorable-risk patients, and they found most postmenopausal patients (aged 50–69) with stage I hormone receptor–positive breast cancer who omitted adjuvant radiation therapy but continued endocrine therapy for 5 years were disease-free 5 years after surgery. These results from the IDEA trial were presented at the 2023 San Antonio Breast Cancer Symposium (SABCS)1 and published simultaneously in the Journal of Clinical Oncology.2 Among 186 evaluable patients, 100% were alive 5 years after lumpectomy, and 99% were free of breast cancer at the time of this analysis.
“This is the first trial to combine a genomic assay and endocrine therapy and to consider younger postmenopausal women with favorable-risk stage I breast cancer for omission of radiotherapy,” stated lead author Reshma Jagsi, MD, DPhil, of Emory University School of Medicine and Winship Cancer Institute. “The omission of radiotherapy plus 5 years of endocrine therapy achieved very low rates of recurrence using the 21-gene recurrence score [≤ 18] in combination with classic clinical and biological features for radiation selection. The time point of 5 years is an early one for these women. Long-term follow-up is essential to determine whether the option of avoiding initial radiation can be offered to a broader range of women than recommended in current guidelines.”
“Long-term follow-up will help to determine whether the option of avoiding initial radiation can be offered to a broader range of women than recommended in current guidelines.”— Reshma Jagsi, MD, DPhil
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Dr. Jagsi shed light on the background of this trial: “Radiation is recommended after lumpectomy to control invasive disease, but not all subgroups get the same benefit. The survival benefit appears restricted to those who have a large absolute risk reduction in recurrence risk from radiotherapy from more than 10% to 20%. Women aged 65 and older with hormone receptor–positive breast cancer can safely omit radiation if they are willing to accept an increased risk of in-breast recurrence. So far, trials in younger patients have been unsuccessful, and it remains unclear whether younger patients can safely be given a choice to consider opting out of adjuvant radiotherapy.”
“Radiation techniques have improved dramatically, and use of five fractions is a significant advance. Radiation therapy is far more tolerable and efficient than it used to be, but patients appreciate having a choice about their treatments,” she told listeners.
Study Details and Results
The prospective, multicenter, single-arm IDEA trial was conducted at 13 sites and screened women with unifocal stage I breast cancer and negative surgical margins after lumpectomy. All women were between the ages of 50 and 69 and had hormone receptor–positive, HER2-negative, node-negative disease. To be eligible for the study, surgical margins had to be at least 2 mm. A total of 60 patients were between the ages of 50 and 59, and 140 patients were between the ages of 60 and 69. Median follow-up was 5.2 years.
The Oncotype DX recurrence score was used to determine each patient’s risk of recurrence based on the genetic profile of their tumors. The 200 patients with a low recurrence score (≤ 18) were eligible to omit radiotherapy after breast-conserving surgery, but they still received standard-of-care adjuvant endocrine therapy for at least 5 years.
At 5 years, one ipsilateral recurrence was reported. Six additional recurrences were reported after 5 years. There were no distant recurrences. The crude rates of overall recurrence were 5% for patients between the ages of 50 and 59 and 3.6% for those between the ages of 60 and 69.
Words of Caution
The entry criteria are important. “Don’t generalize these findings to patients with less extensive surgery than the pathologic nodal evaluation and margin requirements of this study,” warned Dr. Jagsi. “Also, exercise caution if compliance to endocrine therapy is not assured,” she reminded listeners.
“The take-away message from this trial is that younger postmenopausal women who meet the criteria of the IDEA trial should be enrolled in clinical trials [not that they should be offered the option to omit radiotherapy off-trial until longer-term follow-up and additional data from more patients are available]. Newer radiation techniques have much lower toxicity, and we don’t want the headline of the news to scare off women from radiation therapy. If the recurrence score is high, and/or you have an indication the disease is aggressive, you should recommend radiotherapy,” she added.
Ongoing Clinical Trials
The EUROPA trial in Europe is evaluating the omission of hormone therapy. “Every discipline should look at each of our therapies to determine whether we can de-escalate, and I hope we will see trials like EUROPA also in the United States. Currently in the United States, the DEBRA trial is a large ongoing multicenter trial looking at radiotherapy omission,” Dr. Jagsi added. DEBRA is focusing on a similar population as the IDEA trial, and women are being randomly assigned to receive either breast radiotherapy plus endocrine therapy or endocrine therapy alone. This trial should provide more evidence for the safe omission of radiation for some patients with breast cancer.
Additional Comments
“These data are impressive, and of high relevance for women who may want to avoid radiation therapy. Clinical trials such as this one provide a basis for a conversation with patients letting them know that
Carlos L. Arteaga, MD
omission of radiation might be an option. Of note, these favorable-risk patients were all on endocrine therapy as well,” commented session moderator Carlos L. Arteaga, MD, Co--Director of SABCS; Past President of the American Association for Cancer Research; and Director of the Harold K. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center.
DISCLOSURE: Dr. Jagsi has received grants from Genentech, the National Institutes of Health, Doris Duke Charitable Foundation, Susan G. Komen Foundation, and American Cancer Society; has served as an expert witness for Kleinbard LLC & Hawks Quindel Law; and owns stock in Equity Quotient. Dr. Arteaga has served as a scientific advisor to Novartis, Eli Lilly, Merck, AstraZeneca, Daiichi Sankyo, OrigiMed, Immunomedics, Puma Biotechnology, Taiho Oncology, Sanofi, and Susan G. Komen Foundation; and has received grant support from Pfizer, Eli Lilly, and Takeda.
REFERENCES
1. Jagsi R, Griffith K, Harris E, et al: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50–69 with genomically selected favorable stage I breast cancer. 2023 San Antonio Breast Cancer Symposium. Abstract GS02-08. Presented December 7, 2023.
2. Jagsi R, Griffith KA, Harris EE, et al: Omission of radiotherapy after breast-conserving surgery for women with breast cancer with low clinical and genomic risk: Year outcomes of IDEA. J Clin Oncol. December 7, 2023 (early release online).
EXPERT POINT OF VIEW
Invited discussant of the IDEA trial, Andrea V. Barrio, MD, FACS, of Memorial Sloan Kettering Cancer Center, New York, commented: “High-level evidence suggests the omission of radiation therapy in carefully selected patients [with breast cancer] does not affect prognosis. We hope to convince people that we don’t need to radiate everyone.”
Andrea V. Barrio, MD, FACS
Dr. Barrio continued: “The IDEA trial addressed the question of whether tumor biology should be incorporated into decisions for radiation after lumpectomy for women with a lower-risk genomic recurrence score (≤ 18). All women had 5 years of endocrine therapy, and adherence was excellent,” she emphasized. “They are favorable-risk women.”
Questions Remain
According to Dr. Barrio, however, unanswered questions remain. “What is the ideal negative margin width for women in whom radiotherapy is omitted? Can radiotherapy be omitted in women with lobular cancers, given the higher likelihood of multifocality? Are these results applicable to high-grade disease? What is the preferred assay to identify biologically low-risk patients?”
DISCLOSURE: Dr. Barrio reported no conflicts of interest.
