A Novel Digital Educational Strategy Improves Treatment Adherence and Quality of Life in Patients with Multiple Myeloma.

Multiple myeloma, the second most common hematologic malignancy worldwide, is an aggressive disease with high morbidity and mortality rates. Although myeloma remains incurable, new treatments have improved patients' life expectancy and quality of life. However, as these therapies are administered for prolonged and often indefinite periods, their success depends on high treatment adherence and significant patient engagement. This study aimed to evaluate the impact of a novel digital educational strategy on treatment adherence, quality of life, and the development of complications in patients with newly diagnosed myeloma. To this end, a two-arm, randomized, prospective, double-blind study was conducted to compare the conventional educational approach alone or combined with the novel digital strategy. This strategy was based on some principles of the Persuasive Systems Design model and incorporated the educational recommendations of patients and caregivers. Compared to the control group that only received information through the conventional educational approach, patients randomized to the digital strategy showed significantly higher treatment adherence and quality of life, associated with increased functionality and rapid reincorporation into daily routines. The digital strategy empowered patients and caregivers to understand the disease and therapeutic options and helped patients recall treatment information and implement healthy lifestyle habits. These results support that patient-targeted educational strategies can positively influence treatment adherence and thus improve their quality of life.

Increased High Molecular Weight FGF2 in Endocrine-Resistant Breast Cancer.

Endocrine resistance may develop as a consequence of enhanced growth factor signaling. Fibroblast growth factor 2 (FGF2) consists of a low and several high molecular weight forms (HMW-FGF2). We previously demonstrated that antiprogestin-resistant mammary carcinomas display lower levels of progesterone receptor A isoforms (PRA) than B isoforms (PRB). Our aim was to evaluate the role of FGF2 isoforms in breast cancer progression. We evaluated FGF2 expression, cell proliferation, and pathway activation in models with different PRA/PRB ratios. We performed lentiviral infections of different FGF2 isoforms using the human hormone-responsive T47D-YA cells, engineered to only express PRA, and evaluated tumor growth, metastatic dissemination, and endocrine responsiveness. We assessed FGF2 expression and localization in 81 human breast cancer samples. Antiprogestin-resistant experimental mammary carcinomas with low PRA/PRB ratios and T47D-YB cells, which only express PRB, displayed higher levels of HMW-FGF2 than responsive variants. HMW-FGF2 overexpression in T47D-YA cells induced increased tumor growth, lung metastasis, and antiprogestin resistance compared to control tumors. In human breast carcinomas categorized by their PRA/PRB ratio, we found nuclear FGF2 expression in 55.6% of tumor cells. No differences were found between nuclear FGF2 expression and Ki67 proliferation index, tumor stage, or tumor grade. In low-grade tumor samples, moderate to high nuclear FGF2 levels were associated to carcinomas with low PRA/PRB ratio. In conclusion, we show that HMW-FGF2 isoforms are PRB targets which confer endocrine resistance and are localized in the nuclei of breast cancer samples. Hence, targeting intracellular FGF2 may contribute to overcome tumor progression.

Targeting FGFR with BGJ398 in Breast Cancer: Effect on Tumor Growth and Metastasis.

BACKGROUND: Endocrine resistance and metastatic dissemination comprise major clinical challenges for breast cancer treatment. The fibroblast growth factor receptor family (FGFR) consists of four tyrosine kinase transmembrane receptors, involved in key biological processes. Genomic alterations in FGFR have been identified in advanced breast cancer and thus, FGFR are an attractive therapeutic target. However, the efficacy of FGFR inhibitors on in vivo tumor growth is still controversial. OBJECTIVE: The purpose of this study was to evaluate the role of FGFR in tumor growth and breast cancer progression. METHODS: Cell proliferation was assessed by 3H-thymidine uptake and cell counting in primary cultures of endocrine resistant mammary carcinomas and a human cell line, respectively. Tumor transplants and cell injections were used to determine in vivo growth and spontaneous metastasis. FGFR1-3 and αSMA expression were evaluated on primary tumors by immunohistochemistry. RESULTS: Antiprogestin resistant murine transplants and a human xenograft express high levels of total FGFR1-3. In vitro treatment with the FGFR inhibitor, BGJ398, impaired cell proliferation of resistant variants versus vehicle. In vivo, versus control, BGJ398 treatment decreased one out of four resistant tumors, however all tumors showed a decreased epithelial/stromal ratio. Finally, in a model of hormone resistant mammary cancer that spontaneously metastasizes to the lung, BGJ398 decreased the number of mice with lung metastasis. CONCLUSION: FGFR inhibitors are promising tools that require further investigation to identify sensitive tumors. These studies suggest that targeting FGFR combined with other targeted therapies will be useful to impair breast cancer progression.