Medication adherence, medication patterns and preferences for drug therapy in patients with advanced or metastatic breast cancer

The treatment of advanced or metastatic breast cancer (hereafter referred to as mBC) focuses on prolonging patient survival, providing adequate symptom management, and maintaining quality of life (QoL). This includes supportive therapy to prevent or treat potential side effects and handle comorbidities. Adherence to mBC therapy, supportive therapy, and comorbidity medication is highly important in mBC patients, to extend their survival time, but also to alleviate the symptom burden, prevent potential adverse drug reactions, and to promote QoL. However, mBC has been identified as a risk factor for non-adherence. Further potential risk factors for non-adherence may be identified as polypharmacy (i.e. ≥5 concomitant drugs), potentially inappropriate medication (PIM), potential drug-drug interactions (pDDI), and potentially missing drugs (pMD). Yet, the combination of mBC therapy, supportive therapy, and treatment for comorbidities increases the risk for polypharmacy, PIM, pDDI, and pMD. Additionally, a better understanding how mBC patients value different aspects of drug therapy may improve treatment effectiveness, satisfaction and adherence. Considering these preferences in treatment decision making may be an important strategy to improve adherence. At present, there is a paucity of research on adherence to mBC therapies, supportive therapies and comorbidity medication in patients with mBC. Likewise, evidence on medication patterns in mBC patients is scarce and inconsistent. Furthermore, no systematic review so far summarised and compared the treatment preferences of patients with early BC and mBC. Therefore, within this thesis we firstly determined medication adherence in patients with mBC and identified potential influencing factors using self-report and Bavarian cancer registry data. Secondly, we conducted a systematic literature review, summarising and comparing studies evaluating patient preferences for drug therapy for early BC and mBC determined by choice experiments. Thirdly, we assessed medication patterns in mBC patients and detected PIM, pDDI and pMD using data from routine medical records. At baseline, 75.3% and 86.0% of the patients reported being adherent in terms of persistence and quality of execution, respectively. During the follow-up period, no relevant alterations in adherence levels were observed. Supportive therapy and medication for comorbidities were most affected by non-adherence. The most common reasons for non-adherence were medication beliefs, forgetfulness, and side effects. A total of 668 drugs were documented for all mBC patients, including 131 unique substances, of which 44% were mBC therapy, 18% supportive therapy and 38% treatment for comorbidities or supplements. Patients took a median of 6 (IQR = 5-9) concomitant drugs. Polypharmacy was observed in 80.6% of the patients. PIM were identified in 9.7%, pDDI in 12.9%, and pMD in 64.5% of the patients. In the systematic literature review, 34 studies were included in the analysis. Studies evaluated the preferences of patients with early BC (n = 18), mBC (n = 10) or any stage BC (n = 6) on, for example, chemotherapy or endocrine therapy using different types of choice experiments. Regardless of the stage, most patients valued treatment effectiveness in terms of survival gains higher than potential adverse drug reactions. Treatment cost, mode of administration, treatment regimen and monitoring aspects were considered as least important treatment attributes. In addition, preferences concerning 16 different types of adverse drug reactions were described. Due to high heterogeneity within BC stages, a ranking of these adverse drug reactions was not feasible. The findings emphasise the complex relationship between adherence, patient preferences, and medication safety (i.e. polypharmacy, PIM, pDDI, pMD) in mBC. A more personalised, patient-centred approach in clinical practice – incorporating shared decision-making, tailored adherence interventions, and medication monitoring and management – may have the potential to enhance treatment outcomes and improve adherence and QoL in mBC patients. Future adherence research in mBC may focus on tailored interventions considering the type of medication affected by non-adherence and the reasons for non-adherence. Strategies to improve adherence may include the potential deprescribing of medications for comorbidities, digital health applications, and patient involvement in designing and conducting adherence studies.