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Radiotherapy can safely be omitted from treatment plans following breast conserving surgery without jeopardizing recurrence rates for patients aged 55 years and older who have low-grade, T1N0, luminal A breast cancer with a Ki67 expression of 13.25% or less, according to findings from the LUMINA study.
Radiotherapy can safely be omitted from treatment plans following breast conserving surgery without jeopardizing recurrence rates for patients aged 55 years and older who have low-grade, T1N0, luminal A breast cancer with a Ki67 expression of 13.25% or less, according to findings from the LUMINA study (NCT01791829) presented during the 2022 ASCO Annual Meeting.
In the prospective single-arm, cohort study, radiotherapy was omitted from treatment for 500 women with low-risk luminal A breast cancer. After 5 years, there were only 10 local recurrences, for a cumulative local recurrence risk rate of 2.3% (90% CI, 1.3%-3.8%), which was below the cutoff for significance of 5%. The overall survival rate at 5 years was 97.2% (90% CI, 95.9%-98.4%), with just 1 death related to breast cancer, according to lead author Timothy J. Whelan, MD, FASCO.
“Women 55 years and older with a T1N0 grade 1 to 2 luminal A breast cancer following breast conserving surgery treated with endocrine therapy alone had a very low rate of local recurrence at 5 years,” Whelan, who is a professor in the Department of Oncology and Canada Research Chair in Breast Cancer Research at McMaster University, and a radiation oncologist at the Juravinski Cancer Centre in Hamilton, Ontario, Canada, said in a press briefing on the data. “The prospective and controlled nature of this multicenter study supports that such patients are candidates for omission of radiotherapy.”
Across 26 centers in Canada, the study enrolled 500 patients with hormone receptor–positive breast cancer, with estrogen receptor positivity on greater than 1% of cells and the progesterone receptor expressed on more than 20% of cells. All patients had HER2-negative disease. At baseline, patients had undergone lumpectomy and had either started or were planning to start endocrine therapy.
Only those with a Ki67 of 13.25% of less were included in the study. Ki67 testing was completed centrally using a systematic approach of counting cells in 5 random fields at 3 different locations across Canada. “The reliability testing was greater than 0.90, and was up to 0.98, actually. We were very comfortable with the reliability testing in this study,” Whelan said. “Increasingly, Ki67 is being used in many hospital laboratories to look at proliferation in cancer and was recommended recently by the FDA for adjuvant therapy with abemaciclib [Verzenio]."
The mean age of patients in the study was 67 years, with 40% being between the age of 55 and 65, 48% between the age of 65 and 74, and 12% were age 75 and older. The mean tumor size at the time of resection was 1.1 cm, with a tumor of less than 0.5 cm present for 8% of patients, 0.51 to 1.0 cm for 43% of patients, and 1.1 to 2.0 cm for 49% of patients. The tumor grades were 1 (66%) and 2 (34%) and the main endocrine therapies administered were tamoxifen (41%) and an aromatase inhibitor (59%).
“Over the past 2 decades, we have realized the risk of local recurrence has been steadily decreasing. This has been attributed to the detection of smaller screened cancers, better surgical therapies, and more effective hormonal therapy,” Whelan explained. “We now know that breast cancer is composed of many different molecular subtypes, in particular 4. The first subtype, luminal A, is characterized by estrogen receptor positivity and low Ki67, which is a measure of proliferation. This has the lowest risk of recurrence.”
Other efficacy end points favored omitting radiotherapy for patients with luminal A breast cancer. At the 5-year analysis, there were only 8 cases of contralateral breast cancer, for a contralateral recurrence risk of 1.9% (90% CI, 1.1%-3.2%). A recurrence at any location was experienced by 12 patients, for an overall recurrence risk of 2.7% (90% CI, 1.6%-4.1%). The disease-free survival rate, which includes recurrence, second cancers, and death from other causes was 89.9% (90% CI, 87.5%-92.2%).
“Radiotherapy is an inconvenient treatment. It can last daily for up to 5 weeks and it is a costly therapy. It is associated with a number of [adverse] effects [AEs], including early [AEs], like skin irritation and fatigue, and late [AEs], such as breast pain and distortion that can affect how the breast looks and overall quality of life,” said Whelan. “It is also associated with very rare, serious AEs like cardiac disease and second cancers.”
In North America, there are over 300,000 diagnoses per year of invasive breast cancer, Whelan noted. With this rate and prevalence of the luminal A subtype, he predicted these results could lead to the omission of radiotherapy for 30,000 to 40,000 patients per year.
“These exciting data are very reassuring and could impact a large number of patients with cancer who have very low chances of their breast cancer returning even without radiation therapy,” ASCO Expert in radiation oncology Corey W. Speers, MD, PhD, from the University of Michigan Rogel Cancer Center, said. “These findings are the first of a number of recent trials in breast cancer looking at reducing treatments that are still commonly used but that may not be necessary for appropriately selected patients.”
Follow up in the study will continue for a total of 10 years for each patient, to better assess the impact of omitting radiotherapy on long-term recurrence rates, new primary cancers, and survival. The start date of the study was July 2013 (NCT01791829).