A Four-Arm Randomized Clinical Trial of Topical Pain Control for Sentinel Node Radiotracer Injections in Patients with Breast Cancer.

BACKGROUND: Radioactive tracer injections for breast cancer sentinel lymph node mapping can be painful. In this randomized trial, we compared four approaches to topical pain control for radiotracer injections. METHODS: Breast cancer patients were randomized (9 April 2021-8 May 2022) to receive the institutional standard of ice prior to injection (n = 44), or one of three treatments: ice plus a vibrating distraction device (Buzzy®; n = 39), 4% lidocaine patch (n = 44), or 4% lidocaine patch plus ice plus Buzzy® (n = 40). Patients completed the Wong-Baker FACES® pain score (primary outcome) and a satisfaction with pain control received scale (secondary). Nuclear medicine technologists (n = 8) rated perceived pain control and ease of administration for each patient. At study conclusion, technologists rank-ordered treatments. Data were analyzed as intention-to-treat. Wilcoxon rank-sum tests were used to compare pain scores of control versus pooled treatment arms (primary) and then control to each treatment arm individually (secondary). RESULTS: There were no differences in pain scores between the control and treatment groups, both pooled and individually. Eighty-five percent of patients were 'satisfied/very satisfied' with treatment received, with no differences between groups. No differences in providers' perceptions of pain were observed, although providers perceived treatments involving Buzzy© more difficult to administer (p < 0.001). Providers rated lidocaine patch as the easiest, with ice being second. CONCLUSION: In this randomized trial, no differences in patient-reported pain or satisfaction with treatment was observed between ice and other topical treatments. Providers found treatments using Buzzy® more difficult to administer. Given patient satisfaction and ease of administration, ice is a reasonable standard.

Clinical Trials That Have Informed the Modern Management of Breast Cancer.

Randomized controlled trials have informed the historical evolution of breast cancer management, distilling operative and nonoperative treatments to achieve disease control and improve survival while maximizing quality of life and minimizing complications. The authors describe landmark trials investigating and influencing the following aspects of breast cancer care: extent of breast surgery; axillary management; neoadjuvant and adjuvant therapies; and selection of chemotherapy versus endocrine therapy via application of genomic assays.

In vitro sarcoma cells release a lipophilic substance that activates the pain transduction system via TRPV1.

BACKGROUND: Despite success in treating many forms of cancer, pain associated with malignancy remains a serious clinical issue with a poorly understood etiology. This study determined if certain sarcoma cell lines produced a soluble factor that activates the TRPV1 ion channel expressed on nociceptive sensory neurons, thereby activating a major pain transduction system. MATERIALS AND METHODS: Trigeminal ganglia were harvested from rats and cultured. A rhabdomyosarcoma (CRL1598) and osteosarcoma (CRL 1543) cell line were grown to 75% confluency. Conditioned media (CM) was collected after 24 h of exposure and subjected to reverse phase chromatography. Neuronal activation in the presence of CM was measured using iCGRP RIA and calcium imaging after treatment with vehicle or I-RTX, a potent TRPV1 antagonist. Data were analyzed by ANOVA/Bonferroni or t test. RESULTS: The rhabdomyosarcoma CM produced a 4-fold increase in iCGRP release compared with control media (P < 0.001). The osteosarcoma cell line CM produced a 7-fold increase in iCGRP release compared with control media (P < 0.001). This evoked iCGRP release was via TRPV1 activation since the effect was blocked by the antagonist I-RTX. The application of rhabdomyosarcoma CM produced about a 4-fold increase in [Ca(2+)]I levels (P < 0.001), and this effect was blocked by pretreatment with the TRPV1 antagonist, I-RTX. CONCLUSIONS: We have shown that certain sarcoma cell lines produce a soluble, lipophilic factor that activates the peripheral nociceptor transduction system via TRPV1 activation, thereby contributing to cancer pain. Further investigations are needed to develop tumor-specific analgesics that do not produce unwanted or harmful side-effects.

Sarcomas of the Breast.

Sarcoma of the breast is extremely rare and differs from epithelial breast carcinomas in staging and treatment. Diagnostic workup includes breast imaging and core biopsy as in breast epithelial carcinoma. Surgical management is often wide local excision in the form of breast conservation if possible for primary breast sarcoma or total mastectomy. Radiation-associated breast angiosarcomas often require total mastectomy with radical excision of skin. Breast sarcomas have a hematogenous spread so lymph node evaluation is not a part of treatment or staging. Local recurrence rates are high; prognosis remains poor despite on-going advances in the treatment of epithelial breast carcinoma.

Author Correction: Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

This corrects the article DOI: 10.1038/ncomms15908.

Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis.

Most BRCA1-associated breast tumours are basal-like yet originate from luminal progenitors. BRCA1 is best known for its functions in double-strand break repair and resolution of DNA replication stress. However, it is unclear whether loss of these ubiquitously important functions fully explains the cell lineage-specific tumorigenesis. In vitro studies implicate BRCA1 in elimination of R-loops, DNA-RNA hybrid structures involved in transcription and genetic instability. Here we show that R-loops accumulate preferentially in breast luminal epithelial cells, not in basal epithelial or stromal cells, of BRCA1 mutation carriers. Furthermore, R-loops are enriched at the 5' end of those genes with promoter-proximal RNA polymerase II (Pol II) pausing. Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium. Our studies show that Pol II pausing is an important contributor to BRCA1-associated R-loop accumulation and breast cancer development.

Disparities in the Use of Breast-Conserving Therapy Among Patients With Early-Stage Breast Cancer.

IMPORTANCE: Although breast-conserving therapy (BCT) is an accepted modality for treatment of early-stage breast cancer, many women continue to undergo mastectomy. Detailing the factors associated with choice of BCT may assist with overcoming barriers in the use of this treatment modality. OBJECTIVE: To conduct a population-based examination of the factors that influence the use of BCT. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base, we examined the surgical choices of women with stage T1 or T2 breast cancer treated between 1998 and 2011. Logistic regression analysis conducted between September 19, 2013, and August 26, 2014, was used to assess the multivariate association between patient and facility variables and the probability of undergoing BCT. MAIN OUTCOMES AND MEASURES: Factors associated with the use of BCT. RESULTS: A cohort of 727,927 women was identified in the National Cancer Data Base. Use of BCT, determined using odds ratio (OR) and 95% CI, was greater in patients aged 52 to 61 years compared with younger patients (1.14; 1.12-1.15) and in those with the highest educational level (1.16; 1.14-1.19). Rates of BCT were lower in patients without insurance compared with those with private insurance (0.75; 0.72-0.78) and in those with the lowest median income (0.92; 0.90-0.94). Academic cancer programs, US Northeast location, and residence within 27.8 km of a treatment facility were associated with greater BCT rates than were community cancer programs (1.13; 1.11-1.15), Southern location (1.50; 1.48-1.52), and residence farther from a treatment facility (1.25; 1.23-1.27). When comparing BCT use in 1998 with use in 2011, increases were seen across age groups (from 48.2% to 59.7%), in community cancer programs (48.4% in 1998 vs 58.8% in 2011), and in facilities located in the South (45.1% in 1998 vs 55.3% in 2011). CONCLUSIONS AND RELEVANCE: Although the use of BCT has increased during the past 14 years, nonclinical factors, including socioeconomic demographics, insurance, and travel distance to the treatment facility, persist as key barriers to receipt of BCT. Interventions that address these barriers may facilitate further uptake of BCT.

Management of the clinically node-negative axilla in primary and locally recurrent breast cancer.

For patients with primary breast cancer, nodal status remains a key determinant for overall prognosis. Sentinel lymph node biopsy (SLNB) has become standard care for staging patients who have clinically node-negative disease. However, a new dilemma has arisen: how to manage the clinically negative axilla in patients with ipsilateral breast tumor recurrences (IBTRs). Are outcomes in these patients improved with repeat SLNB? Although observational studies suggest SLNB is feasible in patients with IBTR and a clinically node-negative axilla, the overall impact on morality and local recurrence is not yet known as no randomized trials have addressed this issue.

alpha7 nicotinic receptor gene promoter polymorphisms in inbred mice affect expression in a cell type-specific fashion.

Inbred mouse strains display significant differences in their levels of brain alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) expression, as measured by binding of the alpha7-selective antagonist alpha-bungarotoxin. Variations in alpha-bungarotoxin binding have been shown to correlate with an animal's sensitivity to nicotine-induced seizures and sensory gating. In two inbred mouse strains, C3H/2Ibg (C3H) and DBA/2Ibg (DBA/2), the inter-strain binding differences are linked to a restriction length polymorphism in the alpha7 nAChR gene, Chrna7. Despite this finding, the molecular mechanism(s) through which genetic variability in Chrna7 may contribute to alpha7 nAChR expression differences remains unknown. However, studies of the human alpha7 nAChR gene (CHRNA7) previously have demonstrated that CHRNA7 promoter polymorphisms are associated with differences in promoter activity as well as differences in sensory processing. In the present study, a 947-base pair region of the Chrna7 promoter was cloned from both the C3H and DBA/2 inbred mouse strains in an attempt to identify polymorphisms that may underlie alpha7 nAChR differential expression. Sequence analysis of these fragments identified 14 single nucleotide polymorphisms (SNPs). A combination of two of these SNPs affects promoter activity in an in vitro luciferase reporter assay. These results suggest a mechanism through which the Chrna7 promoter genotype may influence interstrain variations in alpha7 nAChR expression.