Impact of Telemedicine on Access to Care for Rural Transgender and Gender-Diverse Youth.

OBJECTIVE: To explore the impact of telemedicine on access to gender-affirming care for rural transgender and gender diverse youth. STUDY DESIGN: A retrospective analysis of data drawn from the electronic medical records of a clinic that provides approximately 10 000 adolescent and young adult visits per year and serves patients seeking gender health care. The no-show rate was examined as a proxy for access to care due to anticipated challenges with recruiting a representative sample of a historically marginalized population. Logistic regression with generalized estimating equations was conducted to model the association between the odds of a no-show visit and covariates of interest. RESULTS: Telemedicine visits, rural home address, gender health visits, longer travel time, and being younger than 18 years old were associated with lower odds of a no-show in univariate models (n = 17 928 visits). In the adjusted model, the OR of no-shows for gender health visits was 0.56 (95% CI 0.42-0.74), adjusting for rurality, telemedicine, age (< or >18 years), and travel time to the clinic. CONCLUSIONS: In this study, telemedicine was associated with reduced no-shows overall, and especially for rural, transgender and gender diverse youth, and patients who hold both identities. Although the no-show rate does not fully capture barriers to access, these findings provide insight into how this vulnerable population may benefit from expanded access to telemedicine for rural individuals whose communities may lack providers with the skills to serve this population.

Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR+ Breast Tumors.

Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor-positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mammary tissues, before tumor initiation and in response to dysbiosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non-tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors.

Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy.

Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We found similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increased cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects.

Impact of the microbiome on cancer progression and response to anti-cancer therapies.

Humans are a colonized with trillions of commensal microorganisms which exert a profound effect on normal host physiology and immune function through an abundance of genetic and metabolic by-products. Although the commensal microbiome has beneficial functions to host physiology, perturbations of the composition of the commensal microbiome or the homeostatic mucosal environment can lead to the induction of immune pathology and systemic inflammation. In the context of cancer progression or response to immune therapy, this inflammation can be detrimental, resulting in tumor growth and the promotion of immune suppression. On the other hand, significant associations have been identified whereby certain commensal microorganisms are able to enhance T cell function or are required for tumor control in cancer patients treated with certain immune therapies and chemotherapies. The focus of this chapter is to highlight the role of the commensal microbiome during tumor progression and in response to immune therapies.

Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer.

It is unknown why some patients with hormone receptor-positive (HR+) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by cross-talk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here, we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination. Using a mouse model of HR+ mammary cancer, we demonstrate that a preestablished disruption of commensal homeostasis results in enhanced circulating tumor cells and subsequent dissemination to the tumor-draining lymph nodes and lungs. Commensal dysbiosis promoted early inflammation within the mammary gland that was sustained during HR+ mammary tumor progression. Furthermore, dysbiosis enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. These effects were recapitulated both by directly targeting gut microbes using nonabsorbable antibiotics and by fecal microbiota transplantation of dysbiotic cecal contents, demonstrating the direct impact of gut dysbiosis on mammary tumor dissemination. This study identifies dysbiosis as a preexisting, host-intrinsic regulator of tissue inflammation, myeloid recruitment, fibrosis, and dissemination of tumor cells in HR+ breast cancer. SIGNIFICANCE: Identification of commensal dysbiosis as a host-intrinsic factor mediating evolution of metastatic breast cancer allows for development of interventions or diagnostic tools for patients at highest risk for developing metastatic disease.See related commentary by Ingman, p. 3539.