For some patients aged 55 or older with early-stage, low-risk breast cancer, endocrine therapy following breast-conserving surgery may be sufficient without the need for postoperative radiation therapy, according to the results of the prospective LUMINA trial, reported at the 2022 ASCO Annual Meeting.1
Patients enrolled in the LUMINA trial had stage I low- to intermediate-grade breast cancer that met the study definition of the luminal A subtype. They were treated with breast-conserving surgery and adjuvant endocrine therapy but no radiation therapy. There was no comparator arm that included radiation. At 5 years, the rate of local recurrence was 2.3% (the primary endpoint); the chance of developing contralateral breast cancer was 1.9%; the rate of disease-free survival was 89.9%; and the overall survival rate was 97.2%.
“Previous studies have shown that other tumor biomarkers can identify patients [with breast cancer] at very low risk of recurrence, thereby omitting chemotherapy, as it is unlikely to offer benefit. The LUMINA results showed that women with low levels of the Ki67 biomarker may avoid outcomes related to radiotherapy, including significant acute and late effects, such as fatigue and rare life-threatening effects of cardiac disease and second cancers,” stated lead author Timothy Joseph Whelan, MD, FASCO, Professor, Department of Oncology; Canada Research Chair in Breast Cancer Research, McMaster University; and a radiation oncologist at the Juravinski Cancer Center, Hamilton, Ontario, Canada. “The findings indicate there is a significant subset of patients with breast cancer who can avoid radiation therapy, which could be practice-changing,” he said.
Timothy Joseph Whelan, MD, FASCO
Study Background and Details
The overall prognosis for early-stage, hormone receptor–positive breast cancer is excellent, with modern treatment approaches resulting in low risk of recurrence and death from cancer for most patients. Our increasing understanding of molecular features of breast cancer can help separate aggressive tumors with higher risk of recurrence from those with low likelihood of recurrence. In this latter group, there is a high likelihood that in many cases we are overtreating the cancer with therapies that add increased toxicity with little to no additional benefit in reducing recurrence or improving survival. There is a need for studies looking at “de-escalation of therapy” in these cancers, with a goal of minimizing side effects without negatively impacting recurrence.
Patients with early-stage, hormone-sensitive breast cancers are generally treated with breast-conserving surgery followed by endocrine therapy. They also usually undergo radiation therapy following surgery to reduce the risk of local recurrence. However, radiation therapy is associated with acute and long-term toxicities and increases the cost of treatment. Modern treatments have reduced the risk of recurrence of breast cancer in patients with luminal A breast cancer, and previous retrospective studies suggest that women older than age 60 who are treated with breast-conserving surgery alone tend to have a low rate of local recurrence (about 4%–5%).2
“The utility of combining clinical pathologic findings with the finding of luminal type A has not been prospectively studied for the ability to guide radiotherapy decision-making,” Dr. Whelan said.
The single-arm, prospective, multicenter cohort included 501 women from 26 centers who were aged 55 or older and identified as having stage 1 (T1N0), low- to intermediate-grade, luminal A breast cancer—defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2-negative, and Ki67 ≤ 13.25). Testing for Ki67 was performed centrally. The women were treated with breast-conserving surgery with surgical margins of at least 1 mm, followed by adjuvant endocrine therapy. They did not receive postsurgical radiation therapy. Patients were followed every 6 months for the first 2 years and then yearly for 5 years. Follow-up will be continued for 10 years.
Julie R. Gralow, MD, FACP, FASCO
“This trial evaluated de-escalation of therapy for breast cancer in better-behaved stage I breast cancers in patients treated with lumpectomy and endocrine therapy but without radiation, which is typically included as standard of care except possibly in the oldest group of patients. The study showed that it was safe to withhold radiation in these older women treated with lumpectomy. This is a narrow population and does not apply to younger women,” said Julie R. Gralow, MD, FACP, FASCO, Chief Medical Officer and Executive Vice President of ASCO, during a press conference.
“This study provides proof of concept, and now the discussion will be how to identify these patients. I have concerns about Ki67 reproducibility between laboratories, and whether this is the best or only way to identify these low risk cancers. Perhaps we could use other methods of defining a good-risk subgroup, including molecular profiling assays commonly used in chemotherapy decision-making,” she suggested.
Expert Point of View
In an e-mail correspondence with The ASCO Post, Deborah Axelrod, MD, Director of Clinical Breast Surgery at NYU Langone Perlmutter Cancer Center, discussed some of the implications of LUMINA. “The big strength of this study is that it is prospective, and many centers participated. It has been supported by other previous studies as well and will define which patients with newly treated breast cancers can omit radiation, which has been the standard of care,” she commented.
Deborah Axelrod, MD
Dr. Axelrod cited some limitations as well, including the need for longer follow-up in these patients, the lack of a comparator arm, and the unknown compliance rate for 5 years of endocrine therapy in this trial. “There may be older patients who prefer radiation therapy—especially accelerated partial-breast irradiation of 1 week to 5 years of endocrine therapy, which was mandated in this study,” Dr. Axelrod wrote. “The takeaway message [from this trial] is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” she added.
DISCLOSURE: Dr. Whelan has received institutional research funding from Exact Sciences. Dr. Gralow has served as a consultant or advisor to Genentech, AstraZeneca, Roche, Novartis, and Seagen. Dr. Axelrod reported no conflicts of interest.
1. Whelan TJ, et al: LUMINA. 2022 ASCO Annual Meeting. Abstract LBA501. Presented June 7, 2022.
2. Liu FF, et al: J Clin Oncol 33:2035-2040, 2015.