Active Surveillance in Older Women With ER+ Breast Cancer

Breast cancer, like most cancers arising in adults, is a disease of aging. Age is one of the most important risk factors, with nearly one third of all breast cancer cases diagnosed in patients older than 70 years and a peak incidence occurring in the 60s to 70s. The vast majority of these cancers are estrogen receptor positive (ER+), and the proportion of ER+ tumors relative to other subtypes increases with age. Consistent with the favorable receptor status (high degree of ER expression with negative HER2 receptor), these tumors grow slowly and are often less aggressive than tumors in younger patients, reflecting that tumorigenesis in these patients may largely be due to chronic exposures to tumor-promoting stimuli. A sizable proportion of older women - defined as those aged 70 years or older - continue screening mammography. Continuation of routine mammography in older patients can lead to overdiagnosis, which is the detection of cancers that would never have caused symptoms or affected lifespan. As breast cancer incidence rises with age but competing risks of death (like heart disease or other illnesses) also increase, many slow-growing tumors identified through screening may not require treatment. However, once diagnosed, these cancers often lead to unnecessary interventions such as surgery, radiation, or endocrine therapy, which carry physical and emotional burdens. Overdiagnosis can also create anxiety, reduce quality of life, and strain healthcare resources, especially when the benefits of early detection decline with age. Overdiagnosis typically encompasses multiple clinical scenarios: first, some tumors are biologically indolent, due to their genomics, tumor microenvironment, and systemic macroenvironment, and not preordained to grow, spread, or kill; second, some small tumors may have the biological potential to grow and spread but will not do so in the patient's lifetime. The overall hypothesis of the ACTIVE trial is that management of small, screen-detected, ER+/HER2- tumors using an active surveillance is safe and feasible.