Is It Time to Reevaluate Radiotherapy Omission in Older Patients With Favorable Early-Stage Breast Cancer?

Abstract

The role of adjuvant radiotherapy (RT) following breastconserving surgery in early-stage breast cancer has been well established based on several landmark clinical trials in the 1970s. 1,2 Subsequent studies 3,4 have suggested that in a subgroup of patients, particularly older women with smaller estrogen receptor (ER)-positive tumors receiving antihormonal therapy, irradiation may not provide as compelling a clinically meaningful benefit. More recently, significant technical 5 and practical 6,7 advances in breast RT have been made, and an emphasis on individual patient-centric care has become the norm. Taken together, these factors beg the question: Is it time to reevaluate the practice of omitting RT in patients 65 years or older with favorable early-stage breast cancer? Foundation for RT OmissionCancer and Leukemia Group (CALGB) 9343 3 and Postoperative Radiotherapy in Minimum-Risk Elderly II (PRIME II) 4 were landmark trials that served as the foundation for RT omission following breast-conserving surgery in older women with early-stage breast cancer. The CALGB 9343 trial included women 70 years or older with clinical stage I (T1N0M0), ER-positive invasive breast cancer. The PRIME II trial included women 65 years or older with clinical stage I (T1-2N0M0, <3 cm), ER-positive invasive breast cancer. Both studies randomized women to adjuvant long-term endocrine therapy (5 years of tamoxifen) with or without whole-breast RT. The 10-year results of both studies are very similar: the addition of whole-breast RT significantly reduced the risk of local and regional recurrence (10% to 1%-2%) with no differences seen in distant metastases or overall survival. It is important to note that CALGB 9343 was not powered to prove noninferiority in terms of survival. Based on these results, adjuvant endocrine therapy alone has been incorporated into the National Comprehensive Cancer Networks guideline (https://www.nccn.org/professionals/ physician_gls/pdf/breast.pdf) as a category 1 recommendation for women 70 years or older with early-stage, ER-positive breast cancer.

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer

“…The Early Breast Cancer Trialists' Cooperative Group (EBCTCG) (4) meta-analysis showed that radiotherapy after breast-conserving therapy, while reducing the overall cumulative recurrence in node negative patients, confers only a modest survival benefit. Omission of RT after breast-conserving therapy in low risk, older patients with smaller, hormone receptor positive (HR+) tumors remains controversial (5)(6)(7) with limited long term level 1 evidence (2,(8)(9)(10)(11)(12). The 5-year results of the PRIME II trial showed that irradiation reduced ipsilateral recurrence from 4.1% to 1.3% in women ≥65 years with pT1-2 (up to 3cm), pN0, HR+ tumors treated by breast-conserving therapy and adjuvant endocrine therapy (9).…”

Prospective Comparison of Hypofractionated Versus Normofractionated Intensity-Modulated Radiotherapy in Breast Cancer: Late Toxicity Results of the Non-Inferiority KOSIMA Trial (ARO2010-3)

“…Additionally, these results in patients over 60 years old are not representative of younger patients, as different healing patterns and tissue regeneration capability could potentially alter the outcomes. Forbye, current trends for low-risk elderly patients (≥ 65-70 years old) include, yet controversial due to increased local failure rates, radiotherapy omission ( 36 – 38 ). The addition of boost in over half of the patients represents another issue of concern per se .…”

American Society of Clinical Oncology 2022 Annual Meeting Highlights for Radiation Oncologists

“…We suggest caution with this interpretation, however, given the nonrandomized single-arm study design, short follow-up, multiple studies showing continued LR rates beyond 5 years for favorable breast cancer, and advances in RT improving both convenience and cost while preserving efficacy. 6 , 7 , 8 , 9 …”