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CHICAGO -- With guidance from Ki67 proliferation marker screening, older women with low-risk luminal A breast cancer can safely avoid radiotherapy, the phase III study found.

Among 500 women with grade 1-2 T1N0 luminal A breast cancer and low levels of the protein Ki67 who underwent lumpectomy followed by treatment with endocrine therapy alone, just 10 experienced a local recurrence within 5 years of surgery, translating into a 5-year rate of 2.3% (90% CI 1.3-3.8), reported Timothy Whelan, MD, of McMaster University and Juravinski Cancer Centre in Hamilton, Ontario, during a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting.

In addition, only eight women developed contralateral breast cancer, for a 5-year rate of 1.9% (90% CI 1.1-3.2), while the 5-year recurrence-free, disease-free, and overall survival rates were 97.3%, 89.9%, and 97.2%, respectively.

"Breast radiotherapy is commonly given after lumpectomy to reduce local recurrence," Whelan noted. "However, it is both inconvenient, with daily treatments for up to 5 weeks, and costly. Furthermore, it is associated with a variety of side effects, including early side effects such as skin irritation and fatigue, late side effects such as breast pain and distortion, and potential rare side effects such as cardiac disease and second cancers."

Considering more than 300,000 women are diagnosed annually with invasive breast cancer in North America, "we estimate these results can apply to 10%-15% of these women" -- representing up to 40,000 women "who could potentially avoid the morbidity, inconvenience, and cost of radiotherapy," he said.

"We've also recognized that breast cancer is composed of many molecular subtypes, including luminal A, characterized by estrogen receptor positivity and low Ki67, which is a measure of proliferation, and has the lowest risk of recurrence," he added. "Our question was whether we can study patients with clinical risk factors that are low, but also this luminal A subtype, and avoid radiotherapy in this group of patients."

"The omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies," commented Deborah Axelrod, MD, of NYU Langone Health's Perlmutter Cancer Center in New York City, who was not involved in the study.

LUMINA's findings are strengthened by the fact that it is a large prospective study, and that the results are supported by past studies, such as the , which showed that foregoing radiation therapy may not impact 10-year survival rates in older patients with hormone receptor-positive breast cancer, she added.

"This is the first molecularly stratified test and trial to see whether we can go above and beyond clinical and pathological variables to identify [patients who can avoid radiotherapy]," said ASCO discussant Corey Wayne Speers, MD, PhD, of the University of Michigan in Ann Arbor. "It really is a personalized approach to identifying these patients. Identifying these patients based on their intrinsic molecular subtype of the tumor, based on the biology, and not just clinical and pathological features, suggests we can really identify these patients who are at very low risk of their cancer coming back."

Whelan pointed out that Ki67 is increasingly being used in many laboratories to look at the proliferation rate of cancers, and that an immunochemistry assay that measures Ki67 expression was recently to determine if adjuvant therapy with abemaciclib (Verzenio) with endocrine therapy should be used in patients with high-risk early breast cancer.

"I think you're going to find that it's going to be done much more commonly over time," he said. He also noted that cancers are routinely tested with multi-gene tests, "which are quite expensive, and mostly for decisions involving chemotherapy."

"But, we don't routinely test small cancers where we're not considering chemotherapy," he added. "So, we wanted to use a test that could be widely adopted and not be too expensive, which is why we chose Ki67. One of the enabling abilities of this test is that it's not too expensive, and can be done in local laboratories."

The single-arm prospective LUMINA trial included 500 women (mean age 67) from 26 centers in Canada. All patients had luminal A subtype breast cancer (defined as estrogen receptor ≥1%, progesterone receptor >20%, HER2-negative, and Ki67 ≤13.25%) and underwent lumpectomy and had planned or started endocrine therapy. Patients will continue to be followed for up to 10 years to study the effects on long-term recurrence and survival.

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