IntroductionApproximately 20% of older patients with breast cancer either present with metastatic disease or develop distant metastases after early breast cancer. The aims of this study were to assess the prevalence of psychosocial problems in older patients with metastatic breast cancer, and to assess longitudinal changes in functional status, psychosocial functioning, and quality of life.MethodsFor this prospective cohort study, patients with metastatic breast cancer aged 70 years and older were recruited in four Dutch hospitals. A baseline geriatric assessment was performed evaluating somatic, functional and psychosocial domains. Self-administered questionnaires were performed at baseline, three and six months: the Groningen Activity Restriction Scale, Geriatric Depression Scale, Loneliness scale, Apathy scale, Distress Thermometer and EORTC-QLQ-C30. Longitudinal changes on these scales were assessed by performing crude and adjusted linear mixed models.ResultsOf the 100 patients that were included and underwent a geriatric assessment, 85 patients completed the baseline self-administered questionnaires. Almost half of the patients (46%) had depressive symptoms, and up to 64% experienced distress. Apathy was present in 53%, and 36% experienced loneliness. Three- and six-month questionnaires were completed by 77 and 72 patients, respectively. Although a significant increase in loneliness between baseline and six months was seen, this size of this change was not clinically relevant. No other longitudinal changes were found.ConclusionThe prevalence of distress, depressive symptoms, apathy and loneliness in older patients with metastatic breast cancer is high. Timely detection, for which a geriatric assessment is effective, could potentially improve quality of life.
Abstract Optimal endocrine therapy for postmenopausal, hormone-receptor positive (HR+) early breast cancer remains a point of discussion. The Tamoxifen Exemestane Adjuvant Multinational (TEAM) phase III trial showed no significant differences for disease free survival (DFS) and overall survival (OS) at 5 years between exemestane monotherapy and sequential treatment (tamoxifen followed by exemestane). We now report disease related outcomes at 10 years of follow-up (FU), and an explorative analysis to assess the predictive value of clinicopathological and immune-related biomarkers. In the TEAM trial, postmenopausal women with HR+ positive early breast cancer were randomly assigned to exemestane alone or sequential therapy. For this analysis, TEAM patients from countries that completed 10 years of FU were included. The primary endpoint was DFS at ten years, analyzed by intention to treat. Secondary outcomes were OS and cumulative incidence of relapse. An explorative per protocol analysis for relapse free survival (RFS) was performed to identify predictive pathological and immunological biomarkers, including centrally determined ER (ER-poor 0-6 vs ER-rich 7-8) and PR (0-4 vs 5-8) Allred scores, and the immunological markers CD8, FoxP3, classical HLA class 1 and HLA-G which were described earlier (Engels et al, Breast Cancer Treat Res, 2015). In total, 6120 patients were eligible for the current analysis, 3075 patients with exemestane monotherapy and 3045 patients randomized to sequential treatment. Median follow up was 9.83 years. DFS was 66.8% in the exemestane group and 66.8% in the sequential group (hazard ratio (HR) 0.96, 95% CI 0.88-1.05, p=0.389). OS was 74% in the exemestane, and 73% in the sequential group, respectively (HR 0.98, 95% CI 0.89-1.09, p=0.737). The cumulative incidence of relapse was 20% and 22% in the exemestane and sequential groups, respectively (HR 0.88, 95% CI 0.79-0.99, p=0.031). In the explorative per protocol analysis (n=4041), Allred score were available for 2996 patients; immunological markers for 1754 patients. Patients with above median numbers of FoxP3-positive T-cells showed a benefit of exemestane monotherapy for RFS (HR 0.56, 95% CI 0.42-0.75, p<0.001) in contrast to patients with low numbers of FoxP3-positive cells (HR 1.0, 95% CI 0.77-1.32, p=0.97, p-value for interaction 0.004). A high tumor differentiation grade was associated with more benefit for exemestane monotherapy (grade 1/2 HR 0.78, 95% CI 0.65-0.94, p=0.01, grade 3/4 HR 0.61, 95% CI 0.49-0.75, p<0.001), with a borderline significant interaction (p=0.07). ER Allred score showed a borderline significant treatment by marker effect interaction (ER-rich HR 0.69 (95% CI 0.58-0.81, p<0.001); ER-poor HR 0.94 (95% CI 0.65-1.34, p=0.71, p for interaction 0.12). After ten years of follow up, both exemestane monotherapy and sequential therapy remain appropriate options for postmenopausal HR+ early breast cancer patients. Interestingly, the number of regulatory T-cells was a predictive factor for the benefit of exemestane monotherapy, which implies a role of the local immune system in endocrine therapy. Furthermore, data suggested that patients with a higher differentiation grade or ER-rich tumor derive more benefit from exemestane monotherapy. Citation Format: Blok EJ, Derks MGM, Kuppen PJK, Meershoek-Klein Kranenbarg EM, Engels CC, Liefers G-J, Putter H, Seynaeve CM, Kroep JR, Nortier JWR, Rea DW, Hasenburg A, Markopoulos CJ, Paridaens R, Bartlett JMS, van de Velde CJH. 10-year follow-up and biomarker discovery for adjuvant endocrine therapy; results of the TEAM trial [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 PD2-07.
