Patient-reported Adherence to Adjuvant Aromatase Inhibitor Therapy Using the Morisky Medication Adherence Scale: An Evaluation of Predictors.

OBJECTIVES: Endocrine therapy is part of standard adjuvant therapy for patients with hormone receptor-positive breast cancer and has been shown to improve recurrence-free and overall survival. However, adherence to endocrine therapy is suboptimal and is difficult to measure. In this study we evaluate the feasibility of using the Morisky Medication Adherence Scale (MMAS) to assess patient adherence to aromatase inhibitor (AI) therapy. METHODS: Patients with stage 1 to 3, hormone receptor-positive breast cancer receiving adjuvant AI therapy were prospectively enrolled on an Institutional Review Board approved protocol. The MMAS questionnaire was administered to each patient and adherence was measured. Information on duration of AI therapy, patient and tumor characteristics, and treatment was collected. A multivariable logit model approach was utilized to evaluate potential barriers to adherence. RESULTS: Between 2011 and 2014, 100 patients were enrolled. The distribution of adherence levels was 13% low, 37% medium, and 50% high. High adherence was reported more frequently in white women (58%), patients with stage 2 and 3 disease (54%), and patients who did not receive chemotherapy (62%). Multivariable analysis demonstrated that higher adherence was more likely in white women compared with African American women (estimated odds ratio=2.8). CONCLUSIONS: Using the MMAS, only 50% of women with stage 1 to 3 breast cancer reported high adherence to AI therapy, consistent with other reports showing suboptimal adherence to adjuvant endocrine therapy. The MMAS allows for the rapid assessment of adherence to oral adjuvant endocrine therapy and is valuable in a busy clinical setting.

Computer assisted quantitative immunofluorescence of tumor tissue marker expression and clinical outcome to chemotherapy in advanced breast cancer patients.

Chemotherapy is frequently used in the treatment of advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to chemotherapy would help optimize advanced breast cancer treatment approaches. Quantitative immunofluorescence (QIF) may be applied to the standardization of protein analysis, resulting in increased sensitivity and reproducibility. In the current pilot study, QIF was used to correlate the expression of beta tubulin III and thymidylate synthase with clinical outcome associated with taxane and capecitabine treatment, respectively. QIF analysis is based on fluorescent dye-labeled monoclonal antibody staining followed by computer-assisted microscopy to measure the expression of molecular markers in tumor samples derived from a retrospective database. The interpretation of the tumor marker expression levels results in classification of breast tumors as sensitive or resistant to a mechanistically related drug. Overall diagnostic accuracy of QIF for taxane based therapy was 88% (CI 75.0 - 95.3) with a positive predictive value of 86% and a negative predictive value of 100%, while diagnostic accuracy QIF for capecitabine therapy was 86% (CI 88.0-96.0) with a positive predictive value of 80% and a negative predictive value of 100%. In this study, QIF showed retrospectively a potential for predictive value when analyzing chemotherapeutic treatments for individual advanced stage breast cancer patients. The predictive power of the QIF for chemotherapy confirms that further studies utilizing larger clinical cohorts are warranted.

The significance of circulating epithelial cells in Breast Cancer patients by a novel negative selection method.

PURPOSE: A negative selection method for the enumeration and characterization of circulating epithelial/cancer cells (CCC) in Breast Cancer (BC) patients is described. This manual procedure yields reproducible results of high sensitivity and selectivity suitable for research laboratories. PATIENTS AND METHODS: We conducted a prospective blood sampling study in 105 women with stage 1-4 BC attending clinics at the University of Maryland Greenebaum Cancer Center to define the prevalence of CCC utilizing our sensitive double gradient centrifugation and magnetic cell sorting CCC detection and enumeration method. CCC were isolated and enumerated from 15 to 20 ml of venous blood drawn before the start of systemic therapy and periodically thereafter for up to 24 months. One or more CCC/sample was considered a positive result. RESULTS: We analyzed 487 samples for the presence of CCC; the median number of samples/patient was 4 (range 1-8). CCC were detected in 56% of patients, 19%-stage 1; 43%-stage 2; 46%-stage 3; 83%-stage 4. The probability of being positive for the presence of CCC is significantly associated with the stage of cancer (P < 0.0001). The frequency of CCC positive patients and samples increased with the advancing stage of disease. Presence of more than 10 CCC/sample was associated with the decreased survival and increased probability of having metastatic disease P = 0.001. CONCLUSIONS: Increasing number of CCC/sample correlates with the adverse outcome and poorer survival (P < 0.0001). Our CCC test based on the negative selection procedure may provide valuable prognostic information.