HER2-targeted treatment for older patients with breast cancer: An expert position paper from the International Society of Geriatric Oncology.

HER2-positive (HER2+) breast cancer (BC) affects older women nearly as frequently as younger ones. Many older patients have cardiovascular comorbidity and risk greater toxicity from therapy. Treatment therefore requires careful consideration, especially since trials include few patients over 65 and so provide limited guidance. A multidisciplinary task force of the International Society of Geriatric Oncology conducted a literature review to make specific recommendations. In the absence of impaired left ventricular ejection fraction, older patients with HER2+ advanced or metastatic BC (MBC) should receive HER2-targeted therapy adjusted to their general condition. Although trastuzumab combined with pertuzumab and docetaxel or paclitaxel is recommended first-line in fit patients, taxanes are difficult in vulnerable ones, making a better-tolerated chemotherapy partner highly desirable. Hormonal therapy with anti-HER2 treatment is an alternative with hormone sensitive tumours. T-DM1 is the standard for fit trastuzumab- and taxane-exposed patients. Lapatinib activity differs from trastuzumab and causes more side effects and drug interactions that are at higher risk in older patients. For fit HER2+ early BC (EBC) patients, chemotherapy plus one year trastuzumab is standard, dual blockade being restricted to high risk and fit patients. Although there is a low level of evidence, using trastuzumab alone (omitting chemotherapy) or enhancing its action through multiple blockade of HER2 and/or the oestrogen receptor pathway may suit vulnerable and frail MBC and EBC patients. Introducing adjuvant therapy lasting less than one year or harnessing neoadjuvant exposure to assess tumour sensitivity and adjust potential rescue treatment accordingly are other key approaches for older patients. These would be particularly helpful for less robust patients or in health systems with limited resources but need further evaluation.