Abstract ES2-3: Treatment of metastatic breast cancer in older adults
Authors: Brain E 
Published: March 2017

Abstract
Estrogen receptors (ER) expression in breast cancer (BC) increasing according to age, hormonotherapy (HT) is the cornerstone of systemic treatment for the older patients with MBC, not differently from the adjuvant setting. However the debate on the best strategy in MBC may be perceived sometimes ironically less intense than in early stages, perhaps because strategy remains then palliative and because cancer competes with life expectancy earlier than when one targets a benefit assessed at 5 years or later, which is at least twice beyond MBC median survival. This unfair view is less and less acceptable with the moving landscape of research on endocrine resistance and BC molecular dissection.
HT is the preferred choice in presence of ER. It has a benefit-risk balance surpassing (CT) and include anti-estrogens, aromatase inhibitors and selective estrogen receptor degraders. Compliance is usually less on an issue compared with earlier stages. It still requires accurate monitoring to avoid forsaking HT too early. Hormone-refractory situations are more difficult to define, depending on treatment previously given and on the timing of relapse, making consensus and guidelines less established. This is particularly true with the growing evidence that agents targeting mTOR (everolimus) or cyclin-dependent kinases 4 and 6 (e.g. palbociclib, ribociclib) may allow circumventing resistance to HT, with unprecedented delays in the need for CT.
CT is indicated straight away in case of ER-negative disease or if the clinical picture suggests a visceral crisis. Single-agent is the preferred choice in order to avoid stacking side effects of polyCT while providing only marginal benefit. Most cytotoxics require dose-reduction in older patients, not that pharmacokinetics data necessarily differ compared with younger adults - on the proviso that end-organs do not show any damage - but rather because functional decline induced by ageing occur in most, with increased risk of side effects of higher grade or earlier onset. Oral CT is attractive but faces similar compliance issues as HT with higher rates of side effects; it is not for any patient, especially in elderly with cognitive impairments. Metronomic or assimilated (weekly, bi/multi weekly) schedules are other appealing strategies: decreased toxicity, simplified prescriptions [flat doses, (semi-)continuous administration], improved compliance, decreased stays in hospital, etc. Anthracylines and taxanes are theoretically considered as first choice. Given their cardiac and neurological toxicity, other agents have been successfully put forward: liposomal anthracyclines, albumin-bound paclitaxel, capecitabine, vinorelbine.
Older patients with HER2-positive MBC and normal cardiac function should receive HER2-targeted therapy, usually with CT if judged fit. Those with cardiac dysfunction should be individually evaluated. In case of ER-positive disease with contraindication to CT, or without life-threatening disease, anti-HER2 therapy plus HT is an option. Skipping CT from standard combination with anti-HER2 therapy through multiple blockade of the HER2 and associated pathways is the main challenge in the future.
More clinical research is needed for the elderly with MBC, with innovative designs including composite/coprimary endpoints and pharmacoguided strategies.
Citation Format: Brain E. Treatment of metastatic breast cancer in older adults [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES2-3.