Introduction: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. Validated prognostic and predictive biomarkers ...are needed to guide treatment decisions and prognostication.
Areas covered: In this review, we discuss established and developing prognostic and predictive biomarkers in TNBC and associated emerging and approved therapies. Biomarkers reviewed include epidermal growth factor receptor (EGFR), vascular endothelial growth factors (VEGF), fibroblast growth factor receptor (FGFR), human epidermal growth factor receptor 2 (HER2), androgen receptor, NOTCH signaling, oxidative stress/redox signaling, microRNAs, TP53 mutation, breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutation/homologous recombination deficiency (HRD), NTRK gene fusion, PI3K/AKT/mTOR, immune biomarkers (programmed death-ligand 1 (PDL1), tumor-infiltrating lymphocytes (TILs), tumor mutational burden (TMB), neoantigens, defects in DNA mismatch repair proteins (dMMR)/microsatellite instability-high (MSI-H)), circulating tumor cells/cell-free DNA, novel targets of antibody-drug conjugates, and residual disease.
Expert opinion: Biomarker-driven care in the management of TNBC is increasing and has helped expand options for patients diagnosed with this subtype of breast cancer. Research efforts are ongoing to identify additional biomarkers and targeted treatment options with the ultimate goal of improving clinical outcomes and survivorship.
During the COVID-19 pandemic, music therapists transitioned services from in-person to telehealth due to health and safety concerns. Though online delivery of music therapy services for autistic ...individuals occurred prior to 2020, the number of North American music therapists using telehealth with autistic clients rose substantially during the pandemic. The current paper's objective was to delineate music therapists' perceptions regarding factors that helped or hindered autistic persons' engagement in online music therapy sessions. In total, 192 participants completed the survey. Qualitative content analysis of an open-ended question identified seven overarching themes regarding the benefits and challenges of telehealth music therapy for autistic clients. Findings were used to create a screening tool to help music therapists evaluate autistic persons' suitability for telehealth and meet the needs of those who can benefit from telehealth music therapy.
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CRISPR/Cas9 genome editing can facilitate efficient deletion of genomic region, but it has not been used to delete an entire chromosome. Here, Adikusuma et al. show proof-of-concept ...for efficient CRISPR-mediated selective chromosome deletion by removing the centromere or shredding the chromosome arm in mouse embryonic stem cells and zygotes.
Breast cancer survivors live longer due to more advanced cancer treatments; however, cardiovascular disease (CVD) is the leading non-cancer cause of death in breast cancer survivors. Previous studies ...have shown that depression is associated with an increased risk of CVD development. This study investigated whether depressive symptoms or mood disorder history, either independently or in combination with cardiotoxic treatments, predicted older cardiopulmonary age using a novel index-the Age Based on Exercise Stress Test (ABEST)-among breast cancer survivors.
Breast cancer survivors (N = 80, ages 26-72, stage I-IIIA) were assessed an average of 53 days (SD = 26) post-surgery, but before adjuvant treatment, and again an average of 32 (SD = 6) months thereafter. At both visits, they reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D), completed the Structured Clinical Interview for DSM-V, and engaged in an exercise stress test to obtain ABEST scores.
Controlling for treatment type, age, education, trunk fat, antidepressant use, and time between visits, longitudinal analyses showed that breast cancer survivors with a mood disorder history had worsening ABEST scores over time, compared to their peers without this history (p = .046). Change in physical activity between Visits 1 and 2 did not mediate this relationship (95% CI: -0.16-0.51). Ancillary analyses provided some additional support for the primary finding, such that those with a mood disorder history trended toward greater decreases in Vo2max, although results were marginally non-significant (p = .095). There were no cross-sectional relationships between depressive symptoms or mood disorder history and ABEST scores (ps>.20). Treatment type did not modulate observed relationships (ps>.22).
Breast cancer survivors with a mood disorder history may experience faster cardiopulmonary aging compared to their peers without such a history, raising risk for CVD.
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a rare peripheral T-cell lymphoma, is increasing in incidence. However, many practitioners who treat patients with breast cancer ...are not aware of this disease.
To assess how BIA-ALCL develops, its risk factors, diagnosis, and subsequent treatment and to disseminate information about this entity to the medical field.
A literature review was performed in an academic medical setting. All review articles, case reports, original research articles, and any other articles relevant to BIA-ALCL were included. Data on BIA-ALCL, such as pathophysiology, patient demographics, presentation, diagnosis, treatment, and outcomes, were extracted. Particular focus was paid to age, time to onset, implant type, initial symptoms, treatment, and survival. The search was conducted in January 2017 for studies published in any year.
After duplicates were excluded, 304 relevant articles were assessed, and 115 were included from the first documented case in August 1997 through January 2017. Thirty review articles, 44 case reports or series, 15 original research articles, and 26 "other" articles (eg, techniques, special topics, letters) were reviewed. A total of 93 cases have been reported in the literature, and with the addition of 2 unreported cases from the Penn State Health Milton S. Hershey Medical Center, 95 patients were included in this systematic review. Almost all documented BIA-ALCL cases have been associated with a textured device. The underlying mechanism is thought to be due to chronic inflammation from indolent infections, leading to malignant transformation of T cells that are anaplastic lymphoma kinase (ALK) negative and CD30 positive. The mean time to presentation is approximately 10 years after implant placement, with 55 of 83 (66%) patients initially seen with an isolated late-onset seroma and 7 of 83 (8%) with an isolated new breast mass. Ultrasonography with fluid aspiration can be used for diagnosis. Treatment must include removal of the implant and surrounding capsule. More advanced disease may require chemotherapy, radiotherapy, and lymph node dissection.
Breast implant-associated anaplastic large cell lymphoma is a rare cancer in patients with breast implants but is increasing in incidence. It is important for all physicians involved in the care of patients with breast implants to be aware of this entity and be able to recognize initial symptoms.
The 2019 coronavirus disease pandemic influenced music therapists to migrate services to online platforms, though some lost clinical hours during the pandemic when telehealth was not a viable option. ...This survey study aimed to ascertain factors that helped music-based therapists to continue serving autistic clients over telehealth during the pandemic. We surveyed 193 accredited music therapists located mainly in Canada and the US. In addition to gathering data on general perceptions of telehealth music therapy and Neurologic Music Therapy (NMT), one-way ANOVAs were applied to determine differences in percent-change loss of clinical hours for music therapists: (1) working in different employment settings; (2) serving children, youth, adults, or a mixture of ages; and (3) practicing NMT or not. The general perception of telehealth music therapy was positive, and NMTs believed that the clear protocols and transformation design model were helpful to them in adapting services to telehealth. There were no significant differences in percent-change of clinical hours among music therapists in different employment settings or serving different client age groups. Music therapists who said they practiced within the NMT treatment model lost a significantly lower percentage of clinical hours with autistic clients than those who did not practice NMT. Possible reasons for this result and the need for further research are discussed.
The purpose of this study is to highlight the experiences of women who are often hidden in what we know and understand about homelessness, and to make policy and practice recommendations for ...women-centred services including adaptations to current housing interventions.
Three hundred survey interviews were conducted with people experiencing homelessness in Calgary, Alberta, Canada. The survey instrument measured socio-demographics, adverse childhood experiences, mental and physical health, and perceived accessibility to resources. Eighty-one women participants were identified as a subsample to be examined in greater depth. Descriptive statistics and logistic regressions were calculated to provide insight into women respondents' characteristics and experiences of homelessness and how they differed from men's experiences.
Women's experiences of homelessness are different from their male counterparts. Women have greater mental health concerns, higher rates of diagnosed mental health issues, suicidal thoughts and attempts, and adverse childhood trauma. The results should not be considered in isolation, as the literature suggests, because they are highly interconnected.
In order to ensure that women who are less visible in their experiences of homelessness are able to access appropriate services, it is important that service provision is both gender specific and trauma-informed. Current Housing First interventions should be adapted to ensure women's safety is protected and their unique needs are addressed.
DNA alkylation represents a major type of DNA damage and is generally unavoidable due to ubiquitous exposure to various exogenous and endogenous sources of alkylating agents. Among the alkylated DNA ...lesions, O 2-alkylthymidines (O 2-alkyldT) are known to be persistent and poorly repaired in mammalian systems and have been shown to accumulate in the esophagus, lung, and liver tissue of rats treated with tobacco-specific N-nitrosamines, i.e., 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N′-nitrosonornicotine (NNN). In this study, we assessed the replicative bypass of a comprehensive set of O 2-alkyldT lesions, with the alkyl group being a Me, Et, nPr, iPr, nBu, iBu, or sBu, in template DNA by conducting primer extension assays with the use of major translesion synthesis DNA polymerases. The results showed that human Pol η and, to a lesser degree, human Pol κ, but not human polymerase ι or yeast polymerase ζ, were capable of bypassing all O 2-alkyldT lesions and extending the primer to generate full-length replication products. Data from steady-state kinetic measurements showed that human Pol η exhibited high frequencies of misincorporation of dCMP opposite those O 2-alkyldT lesions bearing a longer straight-chain alkyl group. However, the nucleotide misincorporation opposite branched-chain lesions was not selective, with dCMP, dGMP, and dTMP being inserted at similar efficiencies, though the total frequencies of nucleotide misincorporation opposite the branched-chain lesions differed and followed the order of O 2-iPrdT > O 2-iBudT > O 2-sBudT. Together, the results from the present study provided important knowledge about the effects of the length and structure of the alkyl group in the O 2-alkyldT lesions on the fidelity and efficiency of DNA replication mediated by human Pol η.
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