SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. It is estimated that approximately 300,590 new cases of breast cancer will be diagnosed in 2023 and about 43,700 individuals will die of the disease, largely due to metastatic recurrence. Breast cancer is the second leading cause of cancer death in women, in the U.S. About 70% of breast tumors express Estrogen Receptors and/or Progesterone Receptors, and Hormone Receptor-positive (HR-positive), HER2-negative breast cancer is the most frequently diagnosed molecular subtype.
Patient undergoing breast conserving surgery, often receive adjuvant breast radiation therapy to reduce the risk of local recurrence. Radiation therapy however is inconvenient, expensive and can be associated with acute and late toxicities. Several previously published trials explored the omission of radiotherapy in low risk patients, following Breast Conservative Surgery. In the CALGB 9343 trial involving women 70 years or older with Stage I, ER-positive breast cancer, treated with Breast Conservative Surgery, locoregional recurrence at 10 years was 10% among those randomly assigned to omission of radiotherapy group and 2% among those assigned to radiotherapy. Similarly, in the PRIME II trial, women 65 years and older with node-negative tumors 3 cm or smaller in size, treated with Breast Conservative Surgery and Endocrine Therapy, had a local recurrence rate of 10% at 10 years when radiation was omitted versus 1% among those assigned to radiotherapy. In the LUMINA trial, women 55 years of age and over with low grade Luminal A breast cancer following Breast Conserving Surgery, Endocrine Therapy and without radiotherapy, had a local recurrence rate of 2.3% at 5 years. These trials provided a new option to elderly patients who wished to avoid radiotherapy
The IDEA (Individualized Decisions for Endocrine therapy Alone) study is a prospective, multicenter cohort trial, initiated at 13 US institutions in 2015. This single-arm study was designed to explore the feasibility of omitting radiotherapy in younger postmenopausal patients with early-stage breast cancer, based on genomic assay, in addition to clinicopathologic risk factors. The IDEA study was inspired by the desire to expand treatment options for de-escalation of therapy for patients with low molecular risk early stage breast cancer, based on prospective clinical data. In this study 200 eligible patients (N=200) were enrolled. This trial included postmenopausal patients 50-69 years of age, with pT1N0 unifocal invasive breast cancer, with margins 2 mm or more after lumpectomy, whose tumors were ER-positive, PR-positive and HER2-negative, with Oncotype DX 21-gene recurrence score of 18 or less. Patients consented to at least 5 years of Endocrine Therapy after lumpectomy and omitting radiotherapy. The mean age was 62 years, mean tumor size was 10 mm and mean 21-gene recurrence score was 11. Histology was ductal in 85% and lobular in 10%, 42.5% had Grade I, 54.5% had Grade II, and 3% had Grade III tumors, respectively, and lymphovascular invasion was present in 14% of tumors. Patients with bilateral disease, a previous personal history of breast cancer, previous radiotherapy to the breast region, or a known carrier of a mutation that predisposes toward breast cancer development (including BRCA-1 and BRCA-2), were excluded. The Primary end point was the rate of locoregional recurrence, 5 years after Breast Conserving Surgery.
With a clinical follow up of at least 56 months among 186 patients, the Overall Survival (OS) and Breast Cancer-Specific Survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99%. Crude rates of Ipsilateral Breast Events for the entire follow up period for patients age 50-59 years and age 60-69 years were 3.3% and 3.6%, respectively, and crude rates of overall recurrence were 5.0% and 3.6%, respectively. No distant recurrences were observed.
It was concluded from this study that high disease control can be accomplished at 5 years after omission of radiotherapy, in postmenopausal patients with pT1N0 unifocal invasive breast cancer with favorable biologic features. The authors added that the IDEA study is the first prospective trial to incorporate a genomic assay of low molecular risk, to identify appropriate candidates for omission of breast radiotherapy.
Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA. Jagsi R, Griffith KA, Harris EE, et al. Published online December 07, 2023. DOI: 10.1200/JCO.23.02270 Journal of Clinical Oncology.
