Management of primary and advanced breast cancer in older unfit patients (medical treatment).

Elderly women constitute a large group of breast cancer patients, and after multidimensional geriatric assessment (MGA) only a minor part of them are found in perfect health (=fit), while the remaining display one or more physical or functional limitations or familial/social problems and are therefore categorized as vulnerable or frail (=unfit). Although randomized trials have not produced modest evidence that surgery impacts on ultimate survival of elderly women with hormone-responsive tumors, there is a general consensus that age alone should not prevent surgical local treatment even in unfit women due to the limited morbidity of breast surgery and to the risk of local progression. Activity and safety of AIs appear comparable in elderly women compared to younger counterparts, although concomitant cardiovascular comorbidity and osteoporosis should be closely monitored. Of note, compliance to oral therapy in unfit women and possible interferences with concomitant medications are still poorly documented issues. With the exception of high-risk node positive and estrogen-receptor negative patients, administration of adjuvant chemotherapy for estrogen-receptor positive unfit patients is rarely recommended since the uncertain gain in relapse-free survival is exceeded by the increased risk of toxicity and competitive causes of death. Endocrine-responsive metastatic disease is managed with one or more lines of endocrine treatment as in younger patients. Single agent sequential chemotherapy regimens are to be preferred to combination regimens, which are usually more toxic with a limited survival gain even in younger patients. When and how dose reductions should be applied to unfit patients is highly controversial. Trastuzumab in association with chemotherapy can be administered to elderly patients presenting HER2 overexpressing tumors, although the risk of cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based combinations increase the activity and also toxicity of taxane chemotherapy, and are not a preferred option.