Systemic Therapy in Older Patients With High-Risk Disease

Abstract

Adjuvant systemic treatments for older patients with breast cancer require constant dose or schedule adjustments of standards established for younger ones. This is mainly due to frailty that increases according to age (40%-50% of signals in all comers after age 70 years) and remains difficult to spot or diagnose accurately and therefore is often overlooked. Older patients are at higher risk to develop side effects whether under chemotherapy, optimized endocrine treatment, or targeted therapies. Pharmacokinetic reflects poorly functional reserves that reduce with aging and is therefore misleading. The demonstration of significant long-term benefits provided by adjuvant treatments is challenged by life expectancy, driven by multimorbidity status that increases with age, competing with cancer outcome. When geriatric assessment is incorporated into the multidisciplinary team, treatment decision process shows 30%-50% changes, de-escalating initial age-agnostic treatment choices in two of three cases. Finally, expectations from treatment vary over the years: In older ones, although not being exclusive, there is a general shift of preference for protecting functionality, cognitive functions, and independence, as summarized in quality of life that many systemic adjuvant treatment may jeopardize. These provocative considerations show importance to pay more attention to expectations expressed by older patients to limit gaps between what is thought by health care professionals as right, often on the basis of dose intensity models strongly engrained in oncology and that older patients may assess counterintuitively differently. The most achieved molecular testing to identify high-risk luminal tumors should be combined with determinant geriatric factors to bring relevant global information in the adjuvant setting for older patients.