The focus of this review deals with the management of elderly patients with early stage
breast cancer, discussing the role of systemic
therapies [endocrine
therapy (ET),
chemotherapy, novel agents] and
radiation therapy (RT). Several studies have evaluated in elderly low risk patients the possibility of omitting the RT but, at the same time, higher locoregional relapse (LR) rates without significant impact on overall survival (OS) were observed in all studies when RT was excluded. Technological improvements [intensity-modulated RT (IMRT),
volumetric modulated arc therapy (VMAT), high dose brachy
therapy (HDBT)] are very useful in order to reduce cosmetic outcome and improve quality of life of frail patients. The optimal sequence of ET, concomitant or sequential to RT, is currently under investigation, and specifically in the elderly it is questioned the possible choice of prolonged
therapy after standard 5 years. Data regarding
chemotherapy suggesting no benefit of OS in endocrine responsive diseases, whereas endocrine non-responsive
breast cancer still showed a better outcome.
Cyclophosphamide,
methotrexate and
5-fluorouracil (
CMF) regimen is recognized as the standard protocol, although age-dependent increase in
therapy related mortality was reported.
Neoadjuvant chemotherapy in elderly showed a lower ratio of pathological complete response in comparison to younger patients, but
triple negative breast cancer patients showed a good prognosis regarding OS, comparable to younger patients. The risk of
cardiotoxicity seems to increase with age, so the use
trastuzumab in this setting is much debated. Currently, other anti-HER2 agents (
pertuzumab,
lapatinib) are used in neoadjuvant setting, but the data on elderly are still premature. Novel molecules are rapidly changing the clinical management of
breast cancer patients but are tested especially in locally advanced and metastatic setting. Among these, particularly interesting are inhibitors of CDK4 and 6,
alpelisib (PI3K
enzymes mutations), immune checkpoint (PD1, PDL1, CTLA4) inhibitors,
atezolizumab. Elderly patients are under-represented in clinical trials, although ageing can be frequently correlated with a decrease in the effectiveness of the immune system. For elderly women, treatment decisions should be individually decided, taking into account the geriatric assessment and limited life expectancy and
tumor characteristics.