Stabilization of c-Myc by the atypical cell cycle regulator, Spy1, decreases efficacy of breast cancer treatments.

PURPOSE: c-Myc is frequently upregulated in breast cancers, however, targeting c-Myc has proven to be a challenge. Targeting of downstream mediators of c-Myc, such as the 'cyclin-like' cell cycle regulator Spy1, may be a viable therapeutic option in a subset of breast cancer subtypes. METHODS: Mouse mammary tumor cells isolated from MMTV-Myc mice and human breast cancer cell lines were used to manipulate Spy1 levels followed by tamoxifen or chemotherapeutic treatment with a variety of endpoints. Patient samples from TNBC patients were obtained and constructed into a TMA and stained for c-Myc and Spy1 protein levels. RESULTS: Over time, MMTV-Myc cells show a decreased response to tamoxifen treatment with increasing levels of Spy1 in the tamoxifen-resistant cells. shRNA against Spy1 re-establishes tamoxifen sensitivity. Spy1 was found to be highly elevated in human TNBC cell and patient samples, correlating to c-Myc protein levels. c-Myc was found to be stabilized by Spy1 and knocking down Spy1 in TNBC cells shows a significant increase in response to chemotherapy treatments. CONCLUSION: Understanding the interplay between protein expression level and response to treatment is a critical factor in developing novel treatment options for breast cancer patients. These data have shown a connection between Spy1 and c-Myc protein levels in more aggressive breast cancer cells and patient samples. Furthermore, targeting c-Myc has proven difficult, these data suggest targeting Spy1 even when c-Myc is elevated can confer an advantage to current chemotherapies.

Addressing the Barriers to Clinical Trials Accrual in Community Cancer Centres Using a National Clinical Trials Navigator:A Cross-Sectional Analysis.

INTRODUCTION: Clinical trials, although academically accepted as the most effective treatment available for cancer patients, poor accrual to clinical trials remains a significant problem. A clinical trials navigator (CTN) program was piloted where patients and/or their healthcare professionals could request a search and provide a list of potential cancer clinical trials in which a patient may be eligible based on their current status and disease. OBJECTIVES: This study examined the outcomes of a pilot program to try to improve clinical trials accrual with a focus on patients at medium to small sized cancer programs. Outcomes examined included patient disposition (referral to and accrual to interventional trials), patient survival, sites of referral to the CTN program. METHODS: One 0.5 FTE navigator was retained. Stakeholders referred to the CTN through the Canadian Cancer Clinical Trials Network. Demographic and outcomes data were recorded. RESULTS: Between March 2019 and February 2020, 118 patients from across Canada used the program. Seven per cent of patients referred were enrolled onto treatment clinical trials. No available trial excluded 39% patients, and 28% had a decline in their health and died before they could be referred or enrolled onto a clinical trial. The median time from referral to death was 109 days in those that passed. CONCLUSION: This novel navigator pilot has the potential to increase patient accrual to clinical trials. The CTN program services the gap in the clinical trials system, helping patients in medium and small sized cancer centres identify potential clinical trials at larger centres.

Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia.

BACKGROUND: Thrombopoietin receptor agonists are new treatments for patients with chronic immune thrombocytopenia (ITP). How one of these agent, romiplostim, has impacted practice patterns, especially the use of intravenous immune globulin (IVIG), has not been evaluated outside of clinical trials. STUDY DESIGN AND METHODS: This was a retrospective cohort study of adult ITP patients treated with romiplostim in four Canadian centers. Patients had primary or secondary ITP and were followed for 1 year before starting weekly romiplostim treatment. We compared IVIG use, clinical outcomes, and cost before and after romiplostim. RESULTS: Twenty-nine patients with ITP received romiplostim. Median age was 54 years (interquartile range [IQR], 45-63 years) and patients had a median of two prior ITP treatments (IQR, 1-4) including splenectomy (n = 7). Median platelet (PLT) count was 23 × 10(9) before and 124 × 10(9) after romiplostim. Median duration of romiplostim treatment was 3.7 months. Patients used a median of two IVIG infusions per year before and 0.7 per year after starting romiplostim (p = 0.16). For patients who received weekly romiplostim for at least 1 month (n = 19), IVIG infusions were three (IQR, 1-5) per year before and 0.7 (IQR, 0.4-1.6) per year after romiplostim. Results were squewed by two high IVIG users. Nineteen (66%) patients discontinued romiplostim treatment during follow-up because of lack of response (n = 8), sustained response (n = 5), toxicities (n = 4), or response to splenectomy (n = 2). Overall health care costs were similar before and after romiplostim when concomitant treatments, nursing resources, and hospitalizations were considered. CONCLUSIONS: Romiplostim was associated with improved PLT counts and fewer IVIG infusions for most ITP patients. In practice, romiplostim was generally not continued long term and was cost neutral for overall ITP management.

Disparities Report: Disparities Among Minority Women With Breast Cancer Living in Impoverished Areas of California.

BACKGROUND: Interaction effects of poverty and health care insurance coverage on overall survival rates of breast cancer among women of color and non-Hispanic white women were explored. METHODS: We analyzed California registry data for 2,024 women of color (black, Hispanic, Asian, Pacific Islander, American Indian, or other ethnicity) and 4,276 non-Hispanic white women (Anglo-European ancestries and no Hispanic-Latin ethnic backgrounds) diagnosed with breast cancer between the years 1996 and 2000 who were then followed until 2011. The 2000 US census categorized rates of neighborhood poverty. Health care insurance coverage was either private, Medicare, Medicaid, or none. Cox regression was used to model rates of survival. RESULTS: A 3-way interaction between ethnicity, health care insurance coverage, and poverty was observed. Women of color inadequately insured and living in poor or near-poor neighborhoods in California were the most disadvantaged. Women of color adequately insured and who lived in such neighborhoods in California were also disadvantaged. The incomes of such women of color were typically lower than the incomes of non-Hispanic white women. CONCLUSIONS: Women of color with or without insurance coverage are disadvantaged in poor and near-poor neighborhoods of California. Such women may be less able to bare the indirect, direct, or uncovered costs of health care for breast cancer treatment.

Colon cancer care and survival: income and insurance are more predictive in the USA, community primary care physician supply more so in Canada.

BACKGROUND: Our research group advanced a health insurance theory to explain Canada's cancer care advantages over America. The late Barbara Starfield theorized that Canada's greater primary care-orientation also plays a critically protective role. We tested the resultant Starfield-Gorey theory by examining the effects of poverty, health insurance and physician supplies, primary care and specialists, on colon cancer care in Ontario and California. METHODS: We analyzed registry data for people with non-metastasized colon cancer from Ontario (n = 2,060) and California (n = 4,574) diagnosed between 1996 and 2000 and followed to 2010. We obtained census tract-based socioeconomic data from population censuses and data on county-level physician supplies from national repositories: primary care physicians, gastroenterologists and other specialists. High poverty neighborhoods were oversampled and the criterion was 10 year survival. Hypotheses were explored with standardized rate ratios (RR) and tested with logistic regression models. RESULTS: Significant inverse associations of poverty (RR = 0.79) and inadequate health insurance (RR = 0.80) with survival were observed in the California, while they were non-significant or non-existent in Ontario. The direct associations of primary care physician (RRs of 1.32 versus 1.11) and gastroenterologist (RRs of 1.56 versus 1.15) supplies with survival were both stronger in Ontario than California. The supply of primary care physicians took precedence. Probably mediated through the initial course of treatment, it largely explained the Canadian advantage. CONCLUSIONS: Poverty and health insurance were more predictive in the USA, community physician supplies more so in Canada. Canada's primary care protections were greatest among the most socioeconomically vulnerable. The protective effects of Canadian health care prior to enactment of the Affordable Care Act (ACA) clearly suggested the following. Notwithstanding the importance of insuring all, strengthening America's system of primary care will probably be the best way to ensure that the ACA's full benefits are realized. Finally, Canada's strong primary care system ought to be maintained.

Multiplicative disadvantage of being an unmarried and inadequately insured woman living in poverty with colon cancer: historical cohort exploration in California.

BACKGROUND: Many Americans diagnosed with colon cancer do not receive indicated chemotherapy. Certain unmarried women may be particularly disadvantaged. A 3-way interaction of the multiplicative disadvantages of being an unmarried and inadequately insured woman living in poverty was explored. METHODS: California registry data were analyzed for 2,319 women diagnosed with stage II to IV colon cancer between 1996 and 2000 and followed until 2014. Socioeconomic data from the 2000 census classified neighborhoods as high poverty (≥30% of households poor), middle (5-29%) or low poverty (<5% poor). Primary health insurance was private, Medicare, Medicaid or none. Comparisons of chemotherapy rates used standardized rate ratios (RR). We respectively used logistic and Cox regression models to assess chemotherapy and survival. RESULTS: A statistically significant 3-way marital status by health insurance by poverty interaction effect on chemotherapy receipt was observed. Chemotherapy rates did not differ between unmarried (39.0%) and married (39.7%) women who lived in lower poverty neighborhoods and were privately insured. But unmarried women (27.3%) were 26% less likely to receive chemotherapy than were married women (37.1%, RR = 0.74, 95% CI 0.58, 0.95) who lived in high poverty neighborhoods and were publicly insured or uninsured. When this interaction and the main effects of health insurance, poverty and chemotherapy were accounted for, survival did not differ by marital status. CONCLUSIONS: The multiplicative barrier to colon cancer care that results from being inadequately insured and living in poverty is worse for unmarried than married women. Poverty is more prevalent among unmarried women and they have fewer assets so they are probably less able to absorb the indirect and direct, but uncovered, costs of colon cancer care. There seem to be structural inequities related to the institutions of marriage, work and health care that particularly disadvantage unmarried women that policy makers ought to be cognizant of as future reforms of the American health care system are considered.

Inferior vena cava filter use at a large community hospital: a retrospective cohort study.

Inferior vena cava (IVC) filters are considered when patients with venous thromboembolism (VTE) develop a contraindication to anticoagulation. Use of IVC filters is increasing, despite associated complications and lack of data on efficacy in reducing VTE-related mortality. We characterized the pattern of IVC filter use at a large community hospital between 2018 and 2022. Specifically, we assessed the indications for IVC filter insertion, filter removal rates, and filter-associated complications. Indications for IVC filters were compared to those outlined by current clinical practice guidelines. We reviewed 120 consecutive filter placement events. The most common indications included recent VTE and active bleeding (40.0%) or need for anticoagulation interruption for surgery (25.8%). Approximately one-third (30.0%) of IVC filters were inserted for indications either not supported or addressed by guidelines. Half (50.0%) of patients had successful removal of their IVC filter. At least 13 patients (10.8%) experienced a filter-related complication. In a large community-based practice, nearly one-third of IVC filters were inserted for indications not universally supported by current practice guidelines. Moreover, most IVC filters were not removed, raising the risk of filter-associated complications, and supporting the need for development of comprehensive guidelines addressing use of IVC filters, and post-insertion monitoring practices.

Presentation and Outcome of Patients with Multiple Myeloma (MM), Single Centre Experience from Windsor Essex Regional Cancer Centre.

Introduction: Outcomes for patients with multiple myeloma has significantly improved through the years. This is mainly related to the use of novel agents. Methods: This is a retrospective study that reviewed presentation and outcome of 139 patients with multiple myeloma at the Windsor Essex Regional Cancer Centre from Jan. 1, 2015 to Dec. 31, 2019. Median age was 71 years and most patients had higher risk disease (65.5% either R ISS stage II or III). 30% had high risk FISH for myeloma including del.17P, t (4:14), t (14:16) and Gain (1q21). In terms of presentation, 38.8% had anemia (hemoglobin <100g/L), 18.7% had hypercalcemia, 74.1% had skeletal lytic lesions, 38.8% had pathologic fracture and 17.3% had plasmacytoma. Results: Almost all (92%) of the patients were treated using at least one novel agent (proteasome inhibitor or immunomodulators [ImiDs]). Cyclophosphamide, bortezomib, and dexamethasone (CyBorD) was the most used treatment regimen (48.9%) followed by bortezomib, melphalan and prednisone (BMP) at 28.8% and lenalidomide, dexamethasone (LenDex) at 14.4%. With respect to response to therapy, 51.8% had at least Very good partial response (VGPR), while 9.4% had progressive disease. 33% had autologous stem cell transplant. After a median follow up of 2.4 years, median overall survival was 3.7 years. 2 years overall survival and relapse-free survival were 70% and 83%, respectively. Discussion: Our study showed comparable outcome for patients with multiple myeloma despite older age and higher risk disease. Outcome is expected to improve with the introduction of more novel agents.

High-impact practices in cancer education and research: Undergraduate students' perceptions of skills and career development.

High-impact practices (HIPs) are educational practices that foster student success. HIPs have not been widely used in cancer education and research despite the need for students to develop key transferable skills and cultivate social responsibility. Our study addresses this need by implementing four community-based learning HIPs within the context of cancer education and research. Each HIP was classified as having low, moderate, or high alignment with the traits of effective HIPs. Undergraduate science students participated in one to four HIPs as a Feedback Participant, General Volunteer, Student Leader, or Cancer Undergraduate Research and Education (CURES) Class Student. We then studied the effect of these HIPs on students' development of knowledge and skills; career interest and preparedness; and social responsibility. Results from self-reported questionnaires showed that HIPs increased students' cancer knowledge and developed their transferable and technical skills. Many students reported that these HIPs strongly impacted their career preparedness; positively influenced their interest in pursuing careers in health or biomedical sciences; and encouraged them to participate in community service activities. Thus, these findings provide new insights into the perceived benefits of HIPs in cancer education and research by undergraduate students.

Does Pre-Emptive Availability of PREDICT 2.1 Results Change Ordering Practices for Oncotype DX? A Multi-Center Prospective Cohort Study.

For early-stage hormone receptor (HR)-positive and HER2-negative breast cancer, tools to estimate treatment benefit include free and publicly available algorithms (e.g., PREDICT 2.1) and expensive molecular assays (e.g., Oncotype DX). There remains a need to identify patients who de-rive the most benefit from molecular assays and where this test may be of poor value. In this multicenter prospective cohort study, we evaluated whether use of PREDICT 2.1 would impact physician decision making. For the first 6 months of the study, data on physician use of both PREDICT 2.1 and Oncotype DX ordering were collected on all newly diagnosed patients eligible for molecular testing. After 6 months, an educational intervention was undertaken to see if providing physicians with PREDICT 2.1 results affects the frequency of Oncotype DX requests. A total of 602 patients across six cancer centers in Ontario, Canada were recruited between March 2020 and November 2021. Providing PREDICT 2.1 results and an educational intervention did not alter the ordering of an Oncotype DX. For patients with low clinical risk, either by clinico-pathologic features or by PREDICT 2.1, the probability of obtaining a high Oncotype DX recurrence score was substantially lower compared to patients with high-clinical-risk disease. The introduction of an educational intervention had no impact on molecular assay requests. However, routine ordering of molecular assays for patients with low-clinical-risk disease is of poor value.

Evaluating and optimizing Acid-pH and Direct Lysis RNA extraction for SARS-CoV-2 RNA detection in whole saliva.

COVID-19 has been a global public health and economic challenge. Screening for the SARS-CoV-2 virus has been a key part of disease mitigation while the world continues to move forward, and lessons learned will benefit disease detection beyond COVID-19. Saliva specimen collection offers a less invasive, time- and cost-effective alternative to standard nasopharyngeal swabs. We optimized two different methods of saliva sample processing for RT-qPCR testing. Two methods were optimized to provide two cost-efficient ways to do testing for a minimum of four samples by pooling in a 2.0 mL tube and decrease the need for more highly trained personnel. Acid-pH-based RNA extraction method can be done without the need for expensive kits. Direct Lysis is a quick one-step reaction that can be applied quickly. Our optimized Acid-pH and Direct Lysis protocols are reliable and reproducible, detecting the beta-2 microglobulin (B2M) mRNA in saliva as an internal control from 97 to 96.7% of samples, respectively. The cycle threshold (Ct) values for B2M were significantly higher in the Direct Lysis protocol than in the Acid-pH protocol. The limit of detection for N1 gene was higher in Direct Lysis at ≤ 5 copies/µL than Acid-pH. Saliva samples collected over the course of several days from two COVID-positive individuals demonstrated Ct values for N1 that were consistently higher from Direct Lysis compared to Acid-pH. Collectively, this work supports that each of these techniques can be used to screen for SARS-CoV-2 in saliva for a cost-effective screening platform.

Mediation of the effects of living in extremely poor neighborhoods by health insurance: breast cancer care and survival in California, 1996 to 2011.

BACKGROUND: We examined the mediating effect of health insurance on poverty-breast cancer care and survival relationships and the moderating effect of poverty on health insurance-breast cancer care and survival relationships in California. METHODS: Registry data for 6,300 women with breast cancer diagnosed between 1996 and 2000 and followed until 2011 on stage at diagnosis, surgeries, adjuvant treatments and survival were analyzed. Socioeconomic data were obtained for residences from the 2000 census to categorize neighborhoods: high poverty (30% or more poor), middle poverty (5%-29% poor) and low poverty (less than 5% poor). Primary payers or health insurers were Medicaid, Medicare, private or uninsured. RESULTS: Evidence of survival mediation was observed for women with node negative breast cancer. The apparent effect of poverty disappeared in the presence of Medicare or private health insurance. Women who were so insured were advantaged on 8-year survival compared to the uninsured or those insured by Medicaid (OR = 1.89). Evidence of payer moderation by poverty was also observed for women with node negative breast cancer. The survival advantaging effect of Medicare or private insurance was stronger in low poverty (OR = 1.81) than it was in middle poverty (OR = 1.57) or in high poverty neighborhoods (OR = 1.16). This same pattern of mediated and moderated effects was also observed for early stage at diagnosis, shorter waits for adjuvant radiation therapy and for the receipt of sentinel lymph node biopsies. These findings are consistent with the theory that more facilitative social and economic capital is available in low poverty neighborhoods, where women with breast cancer may be better able to absorb the indirect and direct, but uncovered, costs of care. As for treatments, main protective effects as well as moderator effects indicative of protection, particularly in high poverty neighborhoods were observed for women with private health insurance. CONCLUSIONS: America's multi-tiered health insurance system mediates the quality of breast cancer care. The system is inequitable and unjust as it advantages the well insured and the well to do. Recent health care reforms ought to be enacted in ways that are consistent with their federal legislative intent, that high quality health care be truly available to all.

Amyloidosis: a case series and review of the literature.

BACKGROUND: Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis. CASE PRESENTATIONS: In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a  69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges. CONCLUSIONS: Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.

Real-world challenges in eligibility for MMR vaccination two years after autologous and allogeneic HSCT.

Measles outbreaks have raised concerns of fatal infections in immunocompromised patients. Canadian guidelines advise administration of live vaccines, such as measles, mumps, and rubella (MMR), two yearsafter hematopoietic stem cell transplant (HSCT) yet studies have not assessed eligibility based on medication contraindications. We retrospectively reviewed the charts of 72 autologous (auto-HSCT) and 68 allogeneic (allo-HSCT) recipients at the Windsor Regional Cancer Center to determine MMR reactivity and eligibility based on administration of contraindicated medications two years post-HSCT. Reactivity to measles, mumps, and rubella in auto-HSCT recipients was 49.1 %, 28.8 %, and 52.3 %, respectively, and in allo-HSCT recipients was 75.6 %, 57.8 %, and 64.4 %, respectively. Immunity to all three components was significantly different between transplant types (p = 0.0002). Nearly 80 % of auto-HSCT patients were on a contraindicated medication at two years compared to 45 % of allo-HSCT recipients. Auto-HSCT recipients require MMR revaccination, but it is contraindicated in a large proportion of patients.

Critical Illness in Migrant Workers in the Windsor-Essex Region: A Descriptive Analysis.

Despite their essential role in Canadian agriculture, migrant workers face numerous healthcare barriers. There is a knowledge gap regarding the healthcare experiences of migrant workers with critical illness in the Windsor-Essex region. Our objective was to collect information on the experiences of migrant workers experiencing a critical illness at Windsor Regional Hospital (WRH) between 31 December 2011 and 31 December 2021. We conducted a retrospective chart review and interviews with migrant workers. We identified 14 migrant workers who presented to WRH with a critical illness over these 10 years. Despite occasional barriers regarding access to care, the migrant workers received an appropriate standard of care in Canada. Five of the fourteen patients identified were repatriated to their home countries. The migrant worker patients interviewed expressed satisfaction with the care they received in Canada but identified repatriation as a specific concern to receiving continuity of care. The health and financial burden imposed by critical illness on migrant workers and their employers makes critically ill workers vulnerable to medical repatriation as a unique social determinant of health. Considering the critical role of migrant workers in Canada's food security, policy changes should be considered to ensure critically ill workers are able to remain until recovery.

Effects of being uninsured or underinsured and living in extremely poor neighborhoods on colon cancer care and survival in California: historical cohort analysis, 1996-2011.

BACKGROUND: We examined the mediating effects of health insurance on poverty-colon cancer care and survival relationships and the moderating effects of poverty on health insurance-colon cancer care and survival relationships among women and men in California. METHODS: We analyzed registry data for 3,291 women and 3,009 men diagnosed with colon cancer between 1996 and 2000 and followed until 2011 on lymph node investigation, stage at diagnosis, surgery, chemotherapy, wait times and survival. We obtained socioeconomic data for individual residences from the 2000 census to categorize the following neighborhoods: high poverty (30% or more poor), middle poverty (5-29% poor) and low poverty (less than 5% poor). Primary health insurers were Medicaid, Medicare, private or none. RESULTS: Evidence of mediation was observed for women, but not for men. For women, the apparent effect of poverty disappeared in the presence of payer, and the effects of all forms of health insurance seemed strengthened. All were advantaged on 6-year survival compared to the uninsured: Medicaid (RR = 1.83), Medicare (RR = 1.92) and private (RR = 1.83). Evidence of moderation was also only observed for women. The effects of all forms of health insurance were stronger for women in low poverty neighborhoods: Medicaid (RR = 2.90), Medicare (RR = 2.91) and private (RR = 2.60). For men, only main effects of poverty and payers were observed, the advantaging effect of private insurance being largest. Across colon cancer care processes, Medicare seemed most instrumental for women, private payers for men. CONCLUSIONS: Health insurance substantially mediates the quality of colon cancer care and poverty seems to make the effects of being uninsured or underinsured even worse, especially among women in the United States. These findings are consistent with the theory that more facilitative social and economic capital is available in more affluent neighborhoods, where women with colon cancer may be better able to absorb the indirect and direct, but uncovered, costs of care.

A geographical analysis of breast cancer clustering in southern Ontario: generating hypotheses on environmental influences.

This article presents the results of spatial analysis of breast cancer clustering in southern Ontario. Data from the Cancer Care Ontario were analyzed using the Scan Statistic at the level of county, with further analysis conducted within counties that were identified as primary clusters at the dissemination area level. The results identified five counties as primary clusters of women diagnosed with breast cancer between 1986 and 2002: Essex (relative risk [RR] =1.096-1.061; p<0.001), Lambton (RR=1.05-1.167), Chatham-Kent (RR=1.133-1.191), Niagara (RR=1.228-1.290) and Toronto (RR=1.152-1.146). The within county analysis revealed several DAs with significantly higher (RR>3, p<0.05) rates of breast cancer, and supports our hypothesis that breast cancer risk in southern Ontario may be associated with industrial and environmental (such as pesticides) pollutants. Further research is needed to verify the environmental links within the identified clusters.

Are we overtreating stage I triple-negative breast cancer in Ontario? A population-based retrospective epidemiological analysis using the ICES database.

Triple-negative breast cancer (TNBC) is associated with inferior outcomes. The use of adjuvant chemotherapy is the mainstay of treatment, and its efficacy was demonstrated to be correlated with tumor size. Different guidelines exist regarding chemotherapy in early-stage TNBC. This study uses ICES database to examine the outcomes of the use of adjuvant chemotherapy in stage I TNBC in Ontario stratified by tumor size. Records of TNBC patients diagnosed in 2012 to 2014 were collected from ICES database. Stage I patients were analyzed by tumor size: T1a (≤ 0.5 cm), T1b (> 0.5 cm and ≤ 1.0 cm), and T1c (> 1.0 cm and ≤ 2.0 cm). Kaplan-Meier curves, log-rank test statistic, and Cox's proportional hazard regression were used to compare differences in overall survival (OS) between chemotherapy and no-chemotherapy groups. Of 610 patients, 183 had tumor sizes ≤ 1 cm, representing stages T1aN0M0 and T1bN0M0, and 427 had tumors > 1 cm to 2 cm, representing stage T1cN0M0. Patients with tumors ≤ 1 cm who received chemotherapy did not have a significant difference in OS compared to the no-chemotherapy group (p = 0.41, hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.021-2.5). However, patients with tumor sizes > 1 cm to 2 cm who received chemotherapy demonstrated significantly better OS compared to those without (p = 0.023, HR = 0.40, 95% CI 0.16-0.86). Patients with TNBC stage T1cN0M0 should receive adjuvant chemotherapy. For TNBC tumors ≤ 1 cm, avoidance of chemotherapy can be considered. Prospective research should further investigate the efficacy of chemotherapy in TNBC stages T1a-bN0M0.Trial Registration University of Windsor REB#16-119.

A review of the totality of evidence in the development of ABP 798, a rituximab biosimilar.

ABP 798 (RIABNI™) is a biosimilar to rituximab reference product (RP), a monoclonal antibody that targets CD20. Approval of ABP 798 was based on the totality of evidence generated using a stepwise approach which began by showing that it is structurally and functionally similar to rituximab RP. This analytical assessment was followed by a demonstration of pharmacokinetic/pharmacodynamic similarity in patients with rheumatoid arthritis. Comparative clinical efficacy and safety of ABP 798 with rituximab RP was demonstrated as a final step in patients with non-Hodgkin lymphoma and in those with rheumatoid arthritis. Overall, the totality of evidence supported the conclusion that ABP 798 is highly similar to rituximab RP and provided scientific justification for extrapolation to other approved indications of rituximab RP.

Frequently used antiemetic agent dexamethasone enhances the metastatic behaviour of select breast cancer cells.

Glucocorticoids, such as dexamethasone (Dex), are used to prevent common side effects induced by chemotherapy and are heavily prescribed for solid cancers such as breast cancer. There is substantial pre-clinical data to support that Dex activation of the glucocorticoid receptor overrides chemotherapy-induced apoptosis in breast cancer cell lines. These findings are compounded by a recent study demonstrating that increased glucocorticoid receptor activation by endogenous stress hormones increased breast cancer heterogeneity and metastasis. Our study is the first to use both in vitro and in vivo models to thoroughly compare the Dex response on the migration of multiple estrogen receptor negative (ER-) and ER+ cancer cell lines. ER+ and ER- breast cancer cell lines were studied to compare their endogenous glucocorticoid activity as well as their metastatic ability in response to Dex treatment. We show that in the ER- breast cancer lines, Dex increases cell numbers, invasiveness, and migration, while decreasing apoptotic ability. Furthermore, we show that following Dex treatment, ER- breast cancer lines migrate further in an in vivo zebrafish model in comparison to ER+ cell lines. The use of ROR1 antibody to block WNT signaling diminished the metastatic properties of ER- cells, however recombinant WNT5A alone was not sufficient to induce migration. Taken together, we demonstrate that Dex treatment exacerbates the metastatic potential of ER- but not ER+ cells. These findings add to the growing body of data stressing the potential adverse role of endogenous and synthetic glucocorticoids in breast cancer biology.