Women as young as 55 years with low-grade luminal A-type breast cancer may avoid radiation treatment altogether following breast-conserving surgery and hormone therapy, according to a Phase III prospective study led by Canadian researchers. They noted that using a molecular biomarker to screen for this breast cancer subtype would allow thousands of women to avoid the inconvenience, high cost, and harsh short- and long-term side effects associated with radiotherapy.
The study, released during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, revealed that only 2 percent of women harboring tumors with this subtype saw their cancer return 5 years after undergoing lumpectomy and endocrine therapy, while omitting radiotherapy (Abstract LBA501).
Each year, more than 300,000 women are diagnosed with invasive breast cancer in North America, a vast majority from the United States, according to Timothy Joseph Whelan, MD, Professor in the Department of Oncology and Canada Research Chair in Breast Cancer Research at McMaster University, as well as a radiation oncologist at the Juravinski Cancer Centre in Ontario, Canada.
"We estimate that these results could apply to about 10-15 percent of these women, so about 30,000 to 40,000 women per year could avoid the morbidity, inconvenience, and cost of radiotherapy," said Whelan, who presented the findings during an ASCO press briefing.
Corey Wayne Spears, MD, PhD, Associate Professor of Radiation Oncology with the Rogel Cancer Center at the University of Michigan in Ann Arbor, said the LUMINA study is the first molecularly stratified test that goes above and beyond clinical and pathological variables-such as age, tumor size, hormone receptor status, grade, and if any tumor cells remain following surgery-to identify these patients with a low risk of recurrence. The trial also was distinguished by the younger age of many of the participating women. Previous studies in women older than 70 years of age showed risk of local recurrence of about 4-5 percent.
"This is a big patient population that included women as young as 55, which is much younger than typically we talk about with radiation omission," said Spears, who was asked by ASCO to comment about the study. "Most of the trials include women that are 65 or older, so this is an opportunity to approach women at a younger age with a molecular subtype that is very reassuring that in 5 years their chances of the cancer coming back are 2 percent."
Historically, patients with low-grade breast cancer undergo breast-conserving surgery followed by endocrine therapy to reduce hormone levels, a spark that triggers the growth and division of breast cancer cells. Low-grade breast cancer is characterized by slow-growing tumors and a higher rate of survival than high-grade breast cancer that is more likely to spread to other parts of the body.
Radiotherapy often has been included as part of this treatment regimen even for low-grade breast tumors, with daily doses of radiation for up to 5 weeks. Early side effects may include skin irritation and fatigue, followed by breast pain and distortion, and potentially other rare but riskier side effects such as cardiac disease and second cancers.
That said, the risk of local recurrence of breast cancer after initial treatment has been steadily decreasing over the past couple of decades thanks to improved detection of small tumors, better surgical techniques, and more effective hormone therapy.
As outlined by Whelan, LUMINA's goal as a prospective study was to understand if omitting radiotherapy following breast-conserving surgery and endocrine therapy in women with low-grade lumina A breast cancer would realize a 5 percent or lower rate of local recurrence in their breast.
Criteria for this single-arm study, launched in 2013 across 26 centers in Canada, included women aged 55 years and older (mean age: 67 years) with low-grade 1 or 2 luminal A-type breast cancer, according to biopsy results. Tumors removed from these patients via lumpectomy were less than 2 centimeters in size, had not spread to surrounding lymph nodes, and were estrogen- and progesterone-positive, in addition to being HER2-negative. Only 13.25 percent or fewer of tumor cells contained a biomarker called Ki-67, strongly associated with tumor cell proliferation and growth and widely used in routine pathological investigation as a proliferation marker. Patients were followed every 6 months for the first 2 years and then yearly.
Five years following initial treatment, only a few patients who underwent breast-conserving surgery with endocrine therapy, while omitting radiotherapy, had any recurrence of their original tumor. Just 10 women experienced the return of the original cancer in the same breast, equivalent to a 2.3 percent rate in this patient group (CR: 1.3-3.8%) 5 years after initial treatment. That rate was well below the team's initial goal of 5 percent.
"We believe that some of the cancers in the 2 percent range were new cancers that are hard to avoid with radiation therapy," Whelan noted. "We feel the benefit of radiation in this group of patients would be very small-like 2 percent versus all the side effects. We feel that most women would want to avoid the radiation for such small benefits."
Only eight women, or 1.9 percent of the patient population, experienced a contralateral breast cancer or a tumor in the other breast after 5 years. Many of these tumors likely were not associated to the original breast tumor in the other breast.
Disease-free survival, including not only recurrence but the risk of any second cancer or death from other causes, was 89.9 percent at 5 years. Only one woman in the treatment cohort died from breast cancer at 5 years, yielding an overall survival at 97.2 percent with recurrence-free survival listed at 97.3 percent.
Spears noted that results from this LUMINA trial are the first of several similar studies expected to be released in the near future. "[These] will really let us understand who can avoid treating with radiation, who is at such low risk of cancer coming back that they don't need to undergo treatment with radiation."
As for next steps, the researchers said the patients in the LUMINA study will continue to be followed for up to 10 years for effects on long-term recurrence and survival.
Warren Froelich is a contributing writer