Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer.
View Article and Find Full Text PDFAmong the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes.
View Article and Find Full Text PDFPurpose: Medication nonadherence is common among patients with breast cancer (BC) and increases BC mortality and complications from comorbidities. There is growing interest in mobile health interventions such as smartphone applications (apps) to promote adherence.
Methods: Use of Medisafe, a medication reminder and tracking app, was tested over 12 weeks among patients on BC treatment and at least one oral medication.
Introduction: Although the prevalence of a pathogenic variant in the BRCA1 and BRCA2 genes is about 1:400 (0.25%) in the general population, the prevalence is as high as 1:40 (2.5%) among the Ashkenazi Jewish population.
View Article and Find Full Text PDFBackground: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective.
View Article and Find Full Text PDFBackground: Telestroke is an established telemedicine method of delivering emergency stroke care. However, not all neurological patients utilizing telestroke service require emergency interventions or transfer to a comprehensive stroke center. To develop an understanding of the appropriateness of inter-hospital neurological transfers utilizing the telemedicine, our study aimed to assess the differences in outcomes of inter-hospital transfers utilizing the service in relation to the need for neurological interventions.
View Article and Find Full Text PDFJ Clin Oncol
August 2023
Inhibiting individual histone deacetylase (HDAC) is emerging as well-tolerated anticancer strategy compared with pan-HDAC inhibitors. Through preclinical studies, we demonstrated that the sensitivity to the leading HDAC6 inhibitor (HDAC6i) ricolinstat can be predicted by a computational network-based algorithm (HDAC6 score). Analysis of ~3,000 human breast cancers (BCs) showed that ~30% of them could benefice from HDAC6i therapy.
View Article and Find Full Text PDFEstrogen receptor (ER) signaling represents the main driver of tumor growth and survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine therapy (ET) alone or in combination with targeted agents constitutes the mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or acquired resistance to ET occurs in a large proportion of cases, mainly due to aberrant activation of ER signaling (i.
View Article and Find Full Text PDFBackground: Chemoprevention with anti-estrogens, such as tamoxifen, raloxifene or aromatase inhibitors, have been shown to reduce breast cancer risk in randomized controlled trials; however, uptake among women at high-risk for developing breast cancer remains low. The aim of this study is to identify provider-related barriers to shared decision-making (SDM) for chemoprevention in the primary care setting.
Methods: Primary care providers (PCPs) and high-risk women eligible for chemoprevention were enrolled in a pilot study and a randomized clinical trial of web-based decision support tools to increase chemoprevention uptake.
Importance: To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk.
Objective: To examine the effects of patient and clinician decision support about BRCA1/2 genetic testing compared with standard education alone.
Design, Setting, And Participants: This clustered randomized clinical trial was conducted at an academic medical center including 67 clinicians (unit of randomization) and 187 patients.
Introduction: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology.
View Article and Find Full Text PDFCombining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for metastatic estrogen receptor positive (ER+) breast cancer patients but its value in earlier stage patients is unclear. We examined evolutionary trajectories of early-stage breast cancer tumors, using single cell RNA sequencing (scRNAseq) of serial biopsies from the FELINE clinical trial (#NCT02712723) of endocrine therapy (letrozole) alone or combined with the CDK inhibitor ribociclib. Despite differences in subclonal diversity evolution across patients and treatments, common resistance phenotypes emerged.
View Article and Find Full Text PDFPurpose: Increasing usage of multigene panel testing has identified more patients with pathogenic or likely pathogenic (P or LP) variants in low-moderate penetrance genes or variants of uncertain significance (VUS). Our study evaluates the association between genetic test results and contralateral prophylactic mastectomy (CPM) among patients with breast cancer.
Methods: We conducted a retrospective cohort study among women diagnosed with unilateral stage 0-III breast cancer between 2013 and 2020 who underwent genetic testing.
Purpose: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy.
Methods: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1).
Purpose: Preclinical data demonstrate STAT3 as an important regulator in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer.
View Article and Find Full Text PDFPurpose: Propranolol regulates angiogenesis in pre-clinical models and reduces distant breast cancer (BC) metastases in observational studies. We assessed the feasibility of combining propranolol with neoadjuvant chemotherapy (NAC) in patients with BC.
Methods: Women with clinical stage II-III BC undergoing NAC [weekly paclitaxel × 12, followed by dose-dense adriamycin/cyclophosphamide (AC) × 4] started propranolol 20 mg PO BID with paclitaxel #1, and increased to 80 mg extended release (ER) PO daily, as tolerated.
Purpose: Biomarker-driven master protocols represent a new paradigm in oncology clinical trials, but their complex designs and wide-ranging genomic results returned can be difficult to communicate to participants. The objective of this pilot study was to evaluate patient knowledge and expectations related to return of genomic results in the Lung Cancer Master Protocol (Lung-MAP).
Methods: Eligible participants with previously treated advanced non-small-cell lung cancer were recruited from patients enrolled in Lung-MAP.
Purpose: COVID-19 has altered healthcare delivery. Previous work has focused on patients with cancer and COVID-19, but little has been reported on healthcare system changes among patients without COVID-19.
Methods: We performed a retrospective study of patients with breast cancer (BC) in New York City between February 1, 2020, and April 30, 2020.
Background: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR).
Methods: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctOHb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane.