Endocrine therapy after breast-conserving surgery may be the only treatment needed in patients aged ≥55 years with low-grade luminal type A breast cancer, sparing them radiation therapy, including its side effects, financial burden, and inconvenience, according to findings from the single-arm LUMINA clinical trial reported at the 2022 American Society of Clinical Oncology Annual Meeting. Low levels of Ki67, a marker of cancer-cell proliferation, was a criterion for enrollment. According to several experts at the meeting, these results highlight the importance of biomarker screening in patients with breast cancer.
All patients enrolled in the study had surgery followed by 5 years of endocrine therapy. Radiation therapy was omitted. The results showed that the outcomes in these patients were similar to historical patients observed after radiation therapy.
At 5 years, the rate of local recurrence was 2.3% (the primary end point); the rate of contralateral breast cancer was 1.9%; the recurrence-free survival rate was 97.3%; the disease-free survival rate was 89.9%; and the overall survival rate was 97.2%. In all, 1 of 13 deaths resulted from breast cancer.
“Previous studies have…suggested that radiation can be omitted for older women aged 65 or older with low-grade breast cancer. The LUMINA results show that women with luminal type A breast cancer and low levels of the Ki67 biomarker can avoid outcomes related to radiotherapy, including significant acute and late effects, such as fatigue and rare life-threatening side effects of cardiac disease and second cancers,” said the study’s lead investigator Timothy Joseph Whelan, MD, FASCO, Professor of Oncology and Canada Research Chair, Health Services Research in Cancer, McMaster University, Hamilton, Ontario.
“These results could apply to 30,000 to 40,000 women in North America. The findings indicate that there is a significant subset of patients with breast cancer—not just older women—who can avoid radiation therapy. This could be practice-changing,” Dr Whelan emphasized.
Luminal A breast cancer is hormone-receptor–positive, HER2-negative, and has low levels of the protein Ki67. It tends to grow more slowly than other subtypes, and is associated with the lowest risk for recurrence. Patients with luminal A are treated with breast-conserving surgery, followed by endocrine therapy, and many patients undergo radiation to reduce the risk for local recurrence. However, radiation therapy is associated with acute and late adverse events, as well as increased costs and the inconvenience of coming to the clinic daily for as long as 5 weeks.
Studies suggest that in women aged >60 years who receive only breast-conserving surgery, the rate of local recurrence is approximately 4% to 5%. The LUMINA study evaluated women aged ≥55 years.
The single-arm, prospective, multicenter cohort included 501 women with luminal A grade breast cancer treated at 26 centers between August 2013 and July 2017. They all underwent breast-conserving surgery for grade 1 or 2 node-negative breast cancer and had surgical margins of ≥1 mm. They were assigned to 5 years of endocrine therapy and were followed for recurrence every 6 months for the first 2 years and then annually for 5 years.
Median age was 67 years, and 88% of patients were aged <75 years. Median tumor size was 1.1 cm. Grade 1 tumors were found in 66% of patients and grade 2 in 34%. Among those receiving endocrine therapy, 41% were taking tamoxifen (Soltamox), and 59% were taking an aromatase inhibitor.
Follow-up will be continued for 10 years to determine the effects on long-term recurrence and survival.
Commenting on the study, Corey Speers, MD, PhD, Assistant Professor of Radiation Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, said, “Congratulations on this very important trial. We have known for a long time from prospective early-stage trials that many women with luminal A subtype are cured with surgery or radiation therapy alone. Historically, we have tried to identify variables such as stage, grade, and size of surgical margins that are associated with better outcomes, and indeed, we can find some patients who would do well without radiation, but this study is the first molecularly-stratified test to evaluate whether we can add intrinsic molecular subtype to clinical pathologic factors to identify women who can safely avoid radiation. A local recurrence rate of less than 5%—really 2.3% at 5 years—is reassuring,” Dr Speers said.