The LUMINA Study Confirms Some Luminal A Breast Cancers Do Not Require Radiotherapy

According to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, the LUMINA study (NCT01791829) demonstrated that radiotherapy can be safely omitted from the course of treatment following breast-conserving surgery without jeopardising recurrence rates for patients aged 55 and older who have low-grade, T1N0, luminal A breast cancer with a Ki67 expression of 13.25 per cent or less.

Radiotherapy was excluded from treatment for 500 women with low-risk luminal A breast cancer in a prospective single-arm, cohort analysis. There were only 10 local recurrences after 5 years, resulting in a cumulative local recurrence risk rate of 2.3 per cent (90 per cent CI, 1.3 per cent -3.8 per cent), which was less than the significance cutoff of 5%. According to the main author Timothy J. Whelan, MD, FASCO, the overall survival rate at 5 years was 97.2 per cent (90 per cent CI, 95.9 per cent -98.4 per cent), with only one death due to breast cancer.

"Women 55 and older with T1N0 grade 1 to 2 luminal A breast cancer treated with endocrine therapy alone after breast-conserving surgery had a very low rate of local recurrence at 5 years," said Whelan, 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. The multicenter study's prospective and controlled nature supports the notion that such patients are candidates for radiation omission.

The trial involved 500 patients with hormone receptor–positive breast cancer from 26 Canadian hospitals, with oestrogen receptor positivity on more than 1% of cells and progesterone receptor positivity on more than 20% of cells. All of the patients had HER2-negative cancer. Patients had had a lumpectomy and had begun or planned to begin endocrine therapy at the start of the study.

The study only included participants with a Ki67 of 13.25 per cent or less. Ki67 testing was carried out in three distinct locations across Canada, employing a systematic approach of counting cells in five random fields. "The reliability testing was higher than 0.90, and in fact reached 0.98." "The dependability testing in this study was quite pleasant for us," Whelan stated. Ki67 is increasingly being employed in hospital laboratories to look at cancer proliferation, and the FDA recently recommended abemaciclib [Verzenio] as adjuvant therapy.

The patients in the study were on average 67 years old, with 40% being between the ages of 55 and 65, 48% being between the ages of 65 and 74, and 12% being 75 and beyond. The average tumour size at the time of resection was 1.1 cm, with fewer than 0.5 cm tumours present in 8% of cases, 0.51 to 1.0 cm tumours in 43% of cases, and 1.1 to 2.0 cm tumours in 49% of cases. The tumours were graded 1 (66%) and 2 (34%), and the main endocrine therapy used were tamoxifen (41%), and an aromatase inhibitor (34%). (59 per cent ).

We've noticed that the danger of local recurrence has been continuously lowering over the last two decades. This has been ascribed to smaller screening tumours being detected earlier, better surgical procedures, and more effective hormone therapy, according to Whelan. We now know that breast cancer is made up of a variety of molecular subtypes, with 4 being the most common. The first subtype, luminal A, is distinguished by oestrogen receptor positivity and a low Ki67 proliferation score. This has the lowest recurrence risk.

For individuals with luminal A breast cancer, various efficacy outcomes favoured skipping radiation. Only 8 cases of contralateral breast cancer were found in the 5-year review, indicating a contralateral recurrence risk of 1.9 per cent (90 per cent CI, 1.1 per cent -3.2 per cent). Twelve patients had a recurrence in any region, yielding a 2.7 per cent total recurrence risk (90 per cent CI, 1.6 per cent -4.1 per cent ). Recurrence, second malignancies, and death from other causes were all included in the disease-free survival percentage of 89.9%. (90 per cent CI, 87.5 per cent -92.2 per cent ).

"Radiotherapy is a time-consuming procedure. It is a pricey therapy that can last up to 5 weeks and lasts everyday. It has a variety of [adverse] consequences [AEs], including early [AEs] like skin irritation and weariness, as well as late [AEs] such breast pain and distortion, which can influence how the breast appears and overall quality of life," Whelan explained. It's also linked to extremely rare and significant side effects like cardiac disease and second malignancies.

Invasive breast cancer is diagnosed in nearly 300,000 people in North America each year, according to Whelan. With this incidence and predominance of the luminal A subtype, he anticipated that 30,000 to 40,000 individuals may be spared from radiotherapy each year.

These exciting data are very reassuring and could impact a large number of cancer patients who have very low chances of their breast cancer returning even without radiation therapy, said Corey W. Speers, MD, PhD, of the University of Michigan Rogel Cancer Center, an ASCO expert in radiation oncology. "These findings are the first in a series of recent breast cancer trials aimed at lowering the usage of medicines that are still widely used but may not be necessary for suitably selected patients."

The study will follow each patient for a total of ten years to better understand the impact of skipping radiotherapy on long-term recurrence rates, new primary malignancies, and survival. The research began in July of 2013. (NCT01791829).