TRK inhibitor in a patient with metastatic triple-negative breast cancer and NTRK fusions identified via cell-free DNA analysis.

Tissue-agnostic indications for targeted therapies have expanded options for patients with advanced solid tumors. The Food and Drug Administration approvals of the programmed death-ligand 1 inhibitor pembrolizumab and the TRK inhibitors larotrectinib and entrectinib provide rationale for next-generation sequencing (NGS) in effectively all advanced solid tumor patients given potential for clinical responses even in otherwise refractory disease. As proof of concept, this case report describes a 64-year-old woman with triple-negative breast cancer refractory to multiple lines of therapy, found to have a rare mutation on NGS which led to targeted therapy with meaningful response. She initially presented with metastatic recurrence 5 years after treatment for a localized breast cancer, with rapid progression through four lines of therapy in the metastatic setting, including immunotherapy, antibody-drug conjugate-based therapy, and chemotherapy. Germline genetic testing was normal. Ultimately, NGS evaluation of cell-free DNA via an 83-gene assay (Guardant Health, Inc.) identified two NTRK3 fusions: an ETV6-NTRK3 fusion associated with the rare secretory breast carcinoma, and CRTC3-NTRK3, a novel fusion partner not previously described in breast cancer. Liver biopsy was sent for whole exome sequencing and RNA-seq analysis of tissue (BostonGene, Inc., Boston, MA, USA), which provided orthogonal confirmation of both the ETV6-NTRK3 and CRTC3-NTRK3 fusions. She was started on the TRK inhibitor larotrectinib with a marked clinical and radiographic response after only 2 months of therapy. The patient granted verbal consent to share her clinical story, images, and data in this case report. This case demonstrates the significant potential benefits of NGS testing in advanced cancer and the lessons we may learn from individual patient experiences.

Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline.Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here.The reviews of this paper are available via the supplemental material section.

Racial differences in genomic testing and receipt of endocrine therapy in early-stage breast cancer.

PURPOSE: Genomic testing in early-stage hormone-positive breast cancer is the standard of care. However, decisions based on genomic testing results are predicated on the assumption that patients receive endocrine treatment. We sought to investigate racial differences in genomic testing and adjuvant treatment in breast cancer. METHODS: A retrospective, population-based hospital registry study using the National Cancer Database. Participants included women with stages I-II, ER + breast cancer between 2010 and 2014. Sociodemographic factors were analyzed. Primary outcomes were the utilization of genomic testing and receipt of endocrine therapy. Logistic regression modeling was used to compute crude and adjusted odds of genomic testing and receipt of endocrine therapy. RESULTS: Among a total sample size of 387,008 patients, 147,863 (38.2%) underwent genomic testing. Older age (≥ 70 years) was associated with a lower adjusted odd of genomic testing (OR 0.33; 95% CI 0.32-0.34, p = < 0.0001). Black patients had lower odds of receiving genomic testing on multivariate analysis compared to Whites (OR 0.82; 95% CI 0.80-0.85, p = < 0.0001). In patients who underwent a genomic test, compared to Whites, Blacks had a lower odds of receiving endocrine therapy (OR 0.86; 95% CI 0.80-0.93, p = < 0.0001) even if they did not receive adjuvant chemotherapy (OR 0.90; 95% CI 0.82-0.98, p = 0.014). CONCLUSIONS: In a national sample of breast cancer patients, Black women are less likely to get genomic testing and receive hormonal therapy, even when adjuvant chemotherapy is omitted. A priority in addressing breast cancer disparities is to ensure adherence to hormonal therapy among all women, including those who do not receive adjuvant chemotherapy.

Novel semi-automated algorithm for high-throughput quantification of adipocyte size in breast adipose tissue, with applications for breast cancer microenvironment.

The size distribution of adipocytes in fat tissue provides important information about metabolic status and overall health of patients. Histological measurements of biopsied adipose tissue can reveal cardiovascular and/or cancer risks, to complement typical prognosis parameters such as body mass index, hypertension or diabetes. Yet, current methods for adipocyte quantification are problematic and insufficient. Methods such as hand-tracing are tedious and time-consuming, ellipse approximation lacks precision, and fully automated methods have not proven reliable. A semi-automated method fills the gap in goal-directed computational algorithms, specifically for high-throughput adipocyte quantification. Here, we design and develop a tool, AdipoCyze, which incorporates a novel semi-automated tracing algorithm, along with benchmark methods, and use breast histological images from the Komen for the Cure Foundation to assess utility. Speed and precision of the new approach are superior to conventional methods and accuracy is comparable, suggesting a viable option to quantify adipocytes, while increasing user flexibility. This platform is the first to provide multiple methods of quantification in a single tool. Widespread laboratory and clinical use of this program may enhance productivity and performance, and yield insight into patient metabolism, which may help evaluate risks for breast cancer progression in patients with comorbidities of obesity. ABBREVIATIONS: BMI: body mass index.

The Impact of Locoregional Treatment on Survival in Patients With Metastatic Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Although systemic therapy is the standard treatment for metastatic breast cancer, the value of locoregional treatment (LRT) of the primary tumor and its impact on survival is controversial. This study evaluates survival outcomes in patients with metastatic breast cancer after receiving LRT (surgery and/or radiation therapy) of the primary tumor. MATERIALS AND METHODS: The National Cancer Database was used to identify 16,128 qualifying cases of metastatic breast cancer who received systemic therapy with or without LRT from 2004 to 2013. Treatment modality was divided into surgery (Sx), radiation therapy (RT), surgery followed by RT (Sx + RT), and no LRT. The median survival and 3-year actuarial survival rates (OS) were analyzed for each treatment group. On multivariate analyses, adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox regression modeling to adjust for patient and clinicopathologic characteristics. RESULTS: Overall, the median follow-up was 28.3 months, and the median survival for all patients was 37.2 months. With 9761 deaths reported, the estimated 3-year OS was 51.3%. The Sx + RT group (n = 2166) had the highest 3-year OS of 69.4%, followed by the Sx group (n = 4293) with 57.6%, the no LRT group (n = 8955) with 44.3%, and the RT group (n = 714) with 41.5% (P < .0001). On multivariate analysis, compared with the no LRT group, a decreased HR was noted in patients receiving Sx (adjusted HR, 0.68; 95% CI, 0.65-0.71; P < .0001) and Sx + RT (adjusted HR, 0.46; 95% CI, 0.43-0.49; P < .0001). CONCLUSION: LRT, especially surgery followed by RT, in addition to systemic therapy, was associated with improved survival in patients with metastatic breast cancer.

Breast Cancer Treatment Delays at an Urban Safety Net Hospital Among Women Experiencing Homelessness.

Disparities in outcomes for vulnerable women is an ongoing problem. Homelessness and breast cancer treatment outcomes is understudied. This is a descriptive study exploring types of homelessness and treatment delays at an urban safety net hospital providing care to a vulnerable patient population.This study is a retrospective chart review of homeless female patients diagnosed with breast cancer between January 1, 2000 and December 31, 2014. Data for this study were acquired from the hospital cancer registry and electronic medical record. All demographic characteristics, time to treatment and factors related to delays to treatment were analyzed descriptively, reporting frequencies and proportions. The total number of individuals analyzed was 24. All except two subjects were delayed to treatment (≥ 30 days from diagnosis to treatment). Most women in this cohort were categorized as chronically homeless (46%) with the rest categorized as transitionally (29%) or episodically (12%) homeless. The majority of subjects (70%) were Black, non-Hispanic. All except one subject were publicly insured (71% Medicaid; 12% Medicare) or uninsured (8%). Regardless of type of homelessness, most subjects were either 30-60 or 60-90 days delayed. Those who were chronically homeless experienced significantly more delays to first treatment (56% of those who were delayed 30-60 days and 57% of those who were delayed 60-90 days; p value 0.006) than those who were episodically or transitionally homeless. Significant delays and barriers to breast cancer treatment exist among women experiencing homelessness. Further studies to improve breast cancer care for homeless women are warranted.

ATYPICAL MACULOPATHY IN A PATIENT WITH LIGHT CHAIN DEPOSITION DISEASE MIMICKING ADVANCED GEOGRAPHIC ATROPHY.

PURPOSE: To report a previously unreported presentation of advanced geographic atrophy of the macula mimicking nonneovascular (dry) age-related macular degeneration in a patient with light chain deposition disease. METHODS: Ocular examination included dilated fundus examination, fundus autofluorescence, full-field electroretinography, and spectral domain optical coherence tomography. PATIENTS: Single-patient case report. RESULTS: Dilated fundus examination demonstrated diffuse loss of the retinal pigment epithelium in a geographic atrophy pattern in the macula and drusenlike deposits localized to the outer retina and retinal pigment epithelium. There were no signs of choroidal neovascularization or retinal pigment epithelium detachments. Fundus autofluorescence demonstrated wide areas of retinal pigment epithelium loss. Full-field electroretinography was normal. Spectral domain optical coherence tomography displayed atrophy of the outer retinal layers. DISCUSSION: This is the first documented case of drusenlike deposits and maculopathy in a patient with light chain deposition disease that mimics advanced geographic atrophy that is typically observed in nonneovascular age-related macular degeneration. Physicians should be aware of the macular changes that can be associated with light chain deposition disease, and patients with light chain deposition disease should be regularly evaluated for associated macular disease.