A novel system to provide information via online YouTube videos and an evaluation of current online information about hereditary breast cancer.

BACKGROUND: The internet, especially YouTube, has become a prominent source of health information. However, the quality and accuracy of medical content on YouTube vary, posing concerns about misinformation. This study focuses on providing reliable information about hereditary breast cancer on YouTube, given its importance for decision-making among patients and families. The study examines the quality and accessibility of such content in Japanese, where limited research has been conducted. METHODS: A nonprofit organization called BC Tube was established in May 2020 to create informative videos about breast cancer. The study analyzed 85 YouTube videos selected using the Japanese keywords "hereditary breast cancer" and "HBOC", categorized into six groups based on the source of upload: BC Tube, hospitals/governments, individual physicians, public-interest organizations/companies, breast cancer survivors, and others. The videos were evaluated based on various factors, including content length, view counts, likes, comments, and the presence of advertisements. The content was evaluated using the PEMAT and DISCERN quality criteria. RESULTS: BC Tube created high-quality videos with high scores on PEMAT understandability, significantly outperforming other sources. Videos from public-interest organizations/companies received the most views and likes, despite their lower quality. Videos from medical institutions and governments were of superior quality but attracted less attention. CONCLUSIONS: Our study emphasizes the importance of promoting accessible, easy-to-understand, and widely recognized medical information online. The popularity of videos does not always correspond to their quality, emphasizing the importance of quality evaluation. BC Tube provides a peer-reviewed platform to disseminate high-quality health information. We need to develop high-quality online health information and encourage the promotion of evidence-based information on YouTube.

Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer.

PURPOSE: We report results from a phase II study assessing the efficacy of the WEE1 inhibitor adavosertib with cisplatin in metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: Patients with mTNBC treated with 0-1 prior lines of chemotherapy received cisplatin 75 mg/m2 i.v. followed 21 days later by cisplatin plus adavosertib 200 mg oral twice daily for five doses every 21 days. The study had 90% power to detect the difference between null (20%) and alternative (40%) objective response rates (ORR) with a one-sided type I error of 0.1: an ORR >30% was predefined as making the regimen worthy of further study. RNA sequencing and multiplex cyclic immunofluorescence on pre- and post-adavosertib tumor biopsies, as well as targeted next-generation sequencing on archival tissue, were correlated with clinical benefit, defined as stable disease ≥6 months or complete or partial response. RESULTS: A total of 34 patients initiated protocol therapy; median age was 56 years, 2 patients (6%) had BRCA2 mutations, and 14 (41%) had one prior chemotherapy. ORR was 26% [95% confidence interval (CI), 13-44], and median progression-free survival was 4.9 months (95% CI, 2.3-5.7). Treatment-related grade 3-5 adverse events occurred in 53% of patients, most commonly diarrhea in 21%. One death occurred because of sepsis, possibly related to study therapy. Tumors from patients with clinical benefit demonstrated enriched immune gene expression and T-cell infiltration. CONCLUSIONS: Among patients with mTNBC treated with 0-1 prior lines, adavosertib combined with cisplatin missed the prespecified ORR cutoff of >30%. The finding of immune-infiltrated tumors in patients with clinical benefit warrants validation.

Phase II study of Radium-223 dichloride combined with hormonal therapy for hormone receptor-positive, bone-dominant metastatic breast cancer.

BACKGROUND: Radium-223 dichloride (Ra-223) is a targeted alpha therapy that induces localized cytotoxicity in bone metastases. We evaluated the efficacy and safety of Ra-223 plus hormonal therapy in hormone receptor-positive (HR+), bone-dominant metastatic breast cancer. METHODS: In this single-center phase II study, 36 patients received Ra-223 (55 kBq/kg intravenously every 4 weeks) up to 6 cycles with endocrine therapy. The primary objective was to determine the clinical disease control rate at 9 months. Secondary objectives were to determine (a) tumor response rate at 6 months, (b) progression-free survival (PFS) durations, and (c) safety. RESULTS: The median number of prior systemic treatments for metastatic disease was 1 (range, 0-4). The disease control rate at 9 months was 49%. The tumor response rate at 6 months was 54% (complete response, 21%; partial, 32%). The median PFS was 7.4 months (95% CI, 4.8-not reached [NR]). The median bone-PFS was 16 months (95% CI, 7.3-NR). There were no grade 3/4 adverse events. CONCLUSIONS: Ra-223 with hormonal therapy showed possible efficacy in HR+ bone-dominant breast cancer metastasis, and adverse events were tolerable. We plan to further investigate the clinical application of Ra-223 in these patients. (NCT02366130).

Bone Metastasis of Breast Cancer.

Bone is the most common site of metastasis for breast cancer. Bone metastasis significantly affects both quality of life and survival of the breast cancer patient. Clinically, complications secondary to bone metastasis include pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Because bone metastasis is extremely common in patients with metastatic breast cancer, clinical management of bone metastases is an important and challenging aspect of treatment in the metastatic setting.The skeleton is a metabolically active organ system that undergoes continuous remodeling throughout life. A delicate balance of the bone-forming osteoblasts and bone-resorbing osteoclasts in the dynamic microenvironment of the skeleton maintains normal bone remodeling and integrity. The presence of metastatic lesions in bone disrupts the normal bone microenvironment and upsets the fine balance between the key components. The changes in the bone microenvironment then create a vicious cycle that further promotes bone destruction and tumor progression.Various therapeutic options are available for bone metastases of breast cancer. Treatment can be tailored for each patient and, often requires multiple therapeutic interventions. Commonly used modalities include local therapies such as surgery, radiation therapy and radiofrequency ablation (RFA) together with systemic therapies such as endocrine therapy, chemotherapy, monoclonal antibody-based therapy, bone-enhancing therapy and radioisotope therapy. Despite the use of various therapeutic modalities, bone metastases eventually become resistant to therapy, and disease progresses.In this chapter, we describe the clinical picture and biological mechanism of bone metastases in breast cancer. We also discuss known risk factors as well as detection and assessment of bone metastases. We present therapeutic options for bone metastasis using a multidisciplinary approach. Further, we describe future directions for bone metastasis management, focusing on novel bone-specific targeted therapies.

Ribociclib Plus Trastuzumab in Advanced HER2-Positive Breast Cancer: Results of a Phase 1b/2 Trial.

BACKGROUND: Signaling through the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway can mediate therapeutic resistance in HER2-positive breast cancer. Preclinical studies have demonstrated that CDK4/6 inhibitors can resensitize resistant HER2-positive breast cancer to anti-HER2 therapies. PATIENTS AND METHODS: We conducted a phase 1b/2 study of ribociclib (400 mg per day on a continuous schedule) plus trastuzumab (6 mg/kg every 3 weeks) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine. There were no restrictions on the number of prior therapy lines. Primary objective was clinical benefit rate at 24 weeks, and secondary objectives included safety, objective response, rate and progression-free survival. The study was enrolled at ClinicalTrials.gov as NCT02657343. RESULTS: From March 2016 to March 2017, 13 patients were enrolled. One patient was found to have HER2-negative disease and did not receive treatment. Median number of prior lines in the metastatic setting was 5 (range, 0-14); 67% had hormone receptor-positive disease. No dose-limiting toxicities were observed during the safety run-in phase, and ribociclib was thus dosed at 400 mg per day continuously for the expansion cohort. Grade 3 adverse events were observed in 4 patients (33.3%) and included neutropenia (n = 2) as well as fatigue and pain in 1 patient each. No grade 4/5 adverse events or QTc prolongation were observed. One patient (8.3%) experienced stable disease > 24 weeks; no objective responses were observed, and median progression-free survival was 1.33 months (95% confidence interval, 0.92-2.57). CONCLUSION: Continuous low-dose ribociclib (400 mg) plus trastuzumab is safe, with no new safety concerns. The limited activity observed in this study suggests that further study of CDK4/6 inhibitor/anti-HER2 combinations should focus on a less pretreated population.