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.

The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care.

Patients, families, healthcare providers and funders face multiple comparable treatment options without knowing which provides the best quality of care. As a step towards improving this, the REthinking Clinical Trials (REaCT) pragmatic trials program started in 2014 to break down many of the traditional barriers to performing clinical trials. However, until other innovative methodologies become widely used, the impact of this program will remain limited. These innovations include the incorporation of near equivalence analyses and the incorporation of artificial intelligence (AI) into clinical trial design. Near equivalence analyses allow for the comparison of different treatments (drug and non-drug) using quality of life, toxicity, cost-effectiveness, and pharmacokinetic/pharmacodynamic data. AI offers unique opportunities to maximize the information gleaned from clinical trials, reduces sample size estimates, and can potentially "rescue" poorly accruing trials. On 2 May 2023, the first REaCT international symposium took place to connect clinicians and scientists, set goals and identify future avenues for investigator-led clinical trials. Here, we summarize the topics presented at this meeting to promote sharing and support other similarly motivated groups to learn and share their experiences.

The COVID-19 pandemic and its effects on follow-up of patients with early breast cancer: A patient survey.

PURPOSE: Despite limited evidence supporting its effectiveness, most guidelines recommend long-term, routinely scheduled in-person surveillance of patients with early breast cancer (EBC). The COVID-19 pandemic led to increased use of virtual care. This survey evaluated patient perspectives on follow-up care. METHODS: Patients with EBC undergoing surveillance were surveyed about follow-up protocols, perceptions, and interest in clinical trials assessing different follow-up strategies. RESULTS: Of 402 approached patients 270 completed the survey (response rate 67%). Median age 62.5 years (range 25-86) and median time since breast cancer diagnosis was 3.8 years (range < 1-33 years). Most (n = 148/244, 60%) were followed by more than one provider. Routine follow-ups with breast examination were mostly conducted by medical/radiation oncologists every 6 months (n = 110/236, 46%) or annually (n = 106/236, 44%). Participants felt routine follow-up was useful to monitor for recurrence, manage side effects of cancer treatment and to provide support/reassurance. Most participants felt regular follow-up care would detect recurrent cancer earlier (n = 214/255, 96%) and increase survival (n = 218/249, 88%). The COVID-19 pandemic reduced the number of in-person visits for 54% of patients (n = 63/117). Patients were concerned this reduction of in-person visits would lead to later detection of both local (n = 29/63, 46%) and distant recurrences (n = 25/63, 40%). While many felt their medical and radiation oncologists were the most suited to provide follow-up care, 55% felt comfortable having their primary care provider (PCP) conduct surveillance. When presented with a scenario where follow-up has no effect on earlier detection or survival, 70% of patients still wanted routine in-person follow-up for reassurance (63%) with the goal of earlier recurrence detection (56%). CONCLUSIONS: Despite limited evidence of effectiveness of routine in-person assessment, patients continue to place importance on regularly scheduled in-person follow-up.

Shorter Durations of Anti-HER2 Therapy for Patients with Early-Stage, HER2-Positive Breast Cancer: The Physician Perspective.

Despite evidence from clinical trials showing the efficacy of shorter durations of therapy, most HER2-positive early breast cancer (EBC) patients receive a year of anti-HER2 therapy. A survey of Canadian oncologists was conducted online, with electronic data collection, and the analysis is reported descriptively. Measures collected included current practices with respect to the duration of adjuvant anti-HER2 therapy, perspectives on data regarding shorter durations of treatment, and interest in further trials on this subject. Responses were received from 42 providers across Canada. Half (50%, 21/42) reported having never recommended 6 months of anti-HER2 therapy. The primary reason physicians consider a shorter duration is in response to treatment-related toxicities (76%, 31/41). Most participants (79%, 33/42) expressed the need for more data to determine which patients can be safely and effectively treated with shorter durations. Patient factors such as young age, initial stage, hormone receptor status, and type of neoadjuvant chemotherapy were attributed to reluctance to offer shorter durations of treatment. Many respondents (83%, 35/42) expressed interest in participating in the proposed clinical trial of 6 months of anti-HER2 therapy. In contemporary Canadian practice, 12 months of anti-HER2 therapy remains the primary practice. Future trials are required to better define the role of shorter treatment durations.

Evaluating the Utility and Privacy of Synthetic Breast Cancer Clinical Trial Data Sets.

PURPOSE: There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques. METHODS: We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk. RESULTS: Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models. DISCUSSION: Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.

A Multi-Centre Randomized Study Comparing Two Standard of Care Chemotherapy Regimens for Lower-Risk HER2-Positive Breast Cancer.

BACKGROUND: Neither paclitaxel plus trastuzumab (P-H) nor docetaxel-cyclophosphamide plus trastuzumab (TC-H) have been prospectively compared in HER2-positive early-stage breast cancer (EBC). A randomized trial was performed to assess the feasibility of a larger study. METHODS: Lower-risk HER2-positive EBC patients were randomized to either P-H or TC-H treatment arms. The co-primary feasibility outcomes were: ≥75% patient acceptability rate, active trial participation of ≥50% of medical oncologists, ≥75% and ≥90% treatment completion, and receipt rate of planned cycles of chemotherapy, respectively. SECONDARY OUTCOMES: Febrile neutropenia (FN) rate, treatment-related hospitalizations, health-related quality of life (HR-QoL) questionnaires. Analyses were performed by per protocol and intention-to-treat. RESULTS: Between May 2019 and March 2021, 49 of 52 patients agreed to study participation (94% acceptability rate). Fifteen (65%) of 23 medical oncologists approached patients. Rates of FN were higher (8.3% vs. 0%) in the TC-H vs. P-H arm. Median (IQR) changes in scores from baseline in FACT-Taxane Trial Outcome Index at 24 weeks were -4 (-10, -1) vs. -6.5 (-15, -2) for TC-H and P-H arms, respectively. CONCLUSIONS: A randomized trial comparing P-H and TC-H was feasible. Expansion to a larger trial would be feasible to explore patient-reported outcomes of these adjuvant HER2 chemotherapy regimens.

Telephone completion of patient self-reporting health history documents by registered nurses: a survey to evaluate its effectiveness and strategies for improvement.

AIM: Prior to the COVID-19 pandemic, cancer patients would complete their self-reporting health history documentation at their initial consultation visit. With the increase in virtual care, a program was established; whereby, a registered nurse (RN) would complete the self-reporting history with the patient by telephone prior to the initial consultation. A survey of RNs and oncologists evaluating the effectiveness of this program is presented. METHODS: Outpatient RNs and medical and radiation oncologists were surveyed at a single Canadian cancer center. The surveys collected demographic information and perceptions around the successes and challenges of this program. RESULTS: Responses were received from 31/42 (74%) RNs and 29/48 (60%) oncologists. RNs reported calling an average of 4 patients/week, and the median time for each call was 20 min. For responding RNs, 21/31 (68%) felt patients were satisfied with the process, and 18/31 (58%) were satisfied with the quality and efficacy of care they were delivering. 25/31 (81%) RNs felt the telephone calls improved care when the patient came to the clinic. All (100%) oncologists were aware of the program, and 86% (25/29) felt it saved time at the consult visit. Areas for improvement included patients completing the forms themselves and including information on current symptoms and drug insurance status. CONCLUSION: COVID-19 has resulted in many changes in oncology practice. Completion of patient self-reported health history documentation by an RN over the telephone prior to consultation visit received positive feedback from both RNs and oncologists. However, this process has considerable RN resource implications.

Can routinely collected administrative data effectively be used to evaluate and validate endpoints used in breast cancer clinical trials? Protocol for a scoping review of the literature.

BACKGROUND: Randomized controlled trials (RCTs) are a critical component of evidence-based medicine and the evolution of patient care. However, the costs of conducting a RCT can be prohibitive. A promising approach toward reduction of costs and lessening of the burden of intensive and lengthy patient follow-up is the use of routinely collected healthcare data (RCHD), commonly called real-world data. We propose a scoping review to identify existing RCHD case definitions of breast cancer progression and survival and their diagnostic performance. METHODS: We will search MEDLINE, EMBASE, and CINAHL to identify primary studies of women with either early-stage or metastatic breast cancer, managed with established therapies, that evaluated the diagnostic accuracy of one or more RCHD-based case definitions or algorithms of disease progression (i.e., recurrence, progression-free survival, disease-free survival, or invasive disease-free survival) or survival (i.e., breast-cancer-free survival or overall survival) compared with a reference standard measure (e.g., chart review or a clinical trial dataset). Study characteristics and descriptions of algorithms will be extracted along with measures of the diagnostic accuracy of each algorithm (e.g., sensitivity, specificity, positive predictive value, negative predictive value), which will be summarized both descriptively and in structured figures/tables. DISCUSSION: Findings from this scoping review will be clinically meaningful for breast cancer researchers globally. Identification of feasible and accurate strategies to measure patient-important outcomes will potentially reduce RCT budgets as well as lessen the burden of intensive trial follow-up on patients. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/6D9RS ).

Regularly scheduled physical examinations and the detection of breast cancer recurrences.

PURPOSE: Follow-up care of early breast cancer (EBC) patients usually includes routinely scheduled physical examinations. While ASCO guidelines recommend a physical exam every three to six months for the first three years, little evidence supports this schedule. We evaluated recurrence detection of patients transferred into a single centre survivorship program that follows ASCO recommendations. METHODS: Patients with EBC referred to the Wellness Beyond Cancer Program (WBCP) who had breast cancer recurrence between February 1, 2013, and January 1, 2019 were reviewed. Descriptive analyses were used to present patient and disease characteristics stratified by type of recurrence and mode of cancer detection. RESULTS: Of 206 recurrences, 135 were distant recurrences (65.5%), 41 were ipsilateral breast recurrences (19.9%), and 30 were contralateral breast primaries (14.6%). Distant recurrences were primarily detected via patient-reported symptoms (125/135, 92.6%). 53.7% (22/41) of ipsilateral breast recurrences were detected by patients and 41.5% (17/41) by routine imaging. Contralateral breast primaries were primarily detected by imaging 83.3% (25/30) and patient-reported symptoms 16.7% (5/30). Only 2/206 (1.14%) recurrences/new primaries were detected by healthcare providers at routinely scheduled follow-up visits. CONCLUSIONS: Despite following ASCO guidelines, healthcare providers rarely detect recurrences at routinely scheduled follow-up appointments. Our data suggests that approximately 35, 000 follow-up visits were required for healthcare providers to detect these 2 recurrences. While reduced in-person visits may affect other aspects of follow-up care (e.g. toxicity management), it appears unlikely, provided patients attend regular screening tests, that less frequent in-person follow-up is associated with worse breast cancer-related outcomes.

Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer.

Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4-12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population.

Does the number of 6-monthly adjuvant zoledronate infusions received affect treatment efficacy for early breast cancer? A sub-study of ABCSG-12.

BACKGROUND: The widespread adoption of adjuvant bisphosphonate therapy for postmenopausal early breast cancer (EBC) patients was based on results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis. Despite multiple regimens evaluated, there was no signal of varying efficacy with type, dose/dose intensity of bisphosphonate administration. We evaluated the effect of early treatment cessation using long-term outcome data from the ABCSG-12 trial. PATIENTS AND METHODS: ABCSG-12 randomized 1803 hormone-receptor positive EBC patients on ovarian suppression between 1999 and 2006 to receive 4 mg zoledronic acid 6-monthly or not (and tamoxifen or anastrozole, 2:2 factorial design). In the current study, we evaluated whether the number of zoledronate infusions had an impact on breast cancer-specific outcomes. We hypothesized that amongst patients who received at least one zoledronate infusion, the number of infusions had no effect on outcomes. Time-to-event endpoints were analysed with Cox models and Kaplan Meier curves starting from a 3-year landmark. BMD analysis was restricted to patients who participated in the BMD sub-study. RESULTS: 725 patients who received at least one zoledronate infusion were included in the time-to-event analysis. There was no statistically significant difference in disease-free or overall survival in the patients who received ≤6 zoledronate infusions (n = 170) compared to those who received ≥7 zoledronate infusions (n = 555). CONCLUSIONS: Comparable to efforts to de-escalate treatment duration in metastatic bone disease, there was no evidence to indicate that a reduced number of zoledronate infusions is associated with reduced adjuvant efficacy. Further studies to define optimal regimens of adjuvant bone-targeted therapies are required.

Management of genitourinary symptoms in patients with breast cancer: an updated systematic review of available evidence from randomized trials.

PURPOSE: The purpose of this systematic review update is to synthesize available data on management of genitourinary symptoms (GUS) in breast cancer patients, a common and challenging clinical scenario. METHODS: EMBASE, Ovid Medline, and the Cochrane Library were searched from September 2014 to December 2021 for randomized controlled trials which examined various interventions for GUS in breast cancer patients. Outcomes of interest included improvements in vaginal symptoms (e.g., dryness, pain, dyspareunia, itching), vaginal hormone response measured by validated scales (e.g., Vaginal Health Index, and Vaginal Maturation Index), and Female Sexual Function Index (FSFI). A team of reviewers participated in the processes of study selection, data collection, and risk of bias appraisal. A descriptive approach to synthesis was used. RESULTS: Of 842 unique citations identified (412 from this update, 430 from previous review), eight studies (n = 539) met inclusion criteria. Interventions included 0.005% estriol gel (EG; n = 50), intravaginal testosterone (IVT; n = 21), intravaginal prebiotic (n = 13), hyaluronic acid (HA; n = 12), polyacrylic acid (PA; n = 25), pH-balanced gel (n = 118), Replens® (n = 24), and Lidocaine (n = 22). These were compared to placebo/saline/lubricants/usual care (n = 228). FSFI total score was significantly improved by all interventions except IVT and lidocaine, and not measured for Replens®. Significant improvements in vaginal hormone responses were reported for EG and pH-balanced gel; however, no significant effects were found for IVT, HA, or prebiotics. Vaginal symptoms were significantly improved by EG, IVT, PA, and PH-balanced gel. CONCLUSION: Treatment of GUS remains a challenging issue. It is evident that more prospective trials are needed.

How Frequently Should Patients with Breast Cancer Have Routine Follow-Up Visits?

Prospective Data Regarding the Optimal Frequency and ModalityProspective data regarding the optimal frequency and modality of follow up after definitive therapy for localized breast cancer is lacking, especially as it relates to time to recurrence detection. This article reviews the evidence and proposes a randomized trial to evaluate on-demand versus guideline-based survivorship care.

Integrating Systematic Reviews into Supportive Care Trial Design: The Rethinking Clinical Trials (REaCT) Program.

PURPOSE: To review the successes and challenges of integrating systematic reviews (SRs) into the Rethinking Clinical Trials (REaCT) Program. METHODS: All REaCT program SRs were evaluated and descriptive summaries presented. RESULTS: Twenty-two SRs have been performed evaluating standard of care interventions for the management of: breast cancer (n = 15), all tumour sites (n = 4), breast and prostate cancers (n = 2), and prostate cancer (n = 1). The majority of SRs were related to supportive care (n = 14) and survivorship (n = 5) interventions and most (19/22, 86%) confirmed the existence of uncertainty relating to the clinical question addressed in the SR. Most SRs (15/22, 68%) provided specific recommendations for future studies and results were incorporated into peer-reviewed grant applications (n = 6) and clinical trial design (n = 12). In 12/22 of the SRs, the first author was a trainee. All SRs followed PRISMA guidelines. CONCLUSION: SRs are important for identifying and confirming clinical equipoise and designing trials. SRs provide an excellent opportunity for trainees to participate in research.

Delivery of cancer care via an outpatient telephone support line: a cross-sectional study of oncology nursing perspectives on quality and challenges.

RATIONALE: Patient support lines (PSLs) assist in triaging clinical problems, addressing patient queries, and navigating a complex multi-disciplinary oncology team. While providing support and training to the nursing staff who operate these lines is key, there is limited data on their experience and feedback. METHODS: We conducted a cross-sectional study of oncology nurses' (ONs') perspectives on the provision of care via PSLs at a tertiary referral cancer center via an anonymous, descriptive survey. Measures collected included nursing and patient characteristics, nature of questions addressed, perceived patient and nursing satisfaction with the service, common challenges faced, and initiatives to improve the patient and nursing experience. The survey was delivered online, with electronic data collection, and analysis is reported descriptively. RESULTS: Seventy-one percent (30/42) of eligible ONs responded to the survey. The most common disease site, stage, and symptom addressed by PSLs were breast cancer, metastatic disease, and pain, respectively. The most common reported issue was treatment-related toxicity (96.7%, 29/30). Sixty-seven percent (20/30) of respondents were satisfied with the care provided by the service; however, many areas for potential improvement were identified. Fifty-nine percent (17/29) of respondents recommended redefining PSLs' responsibilities for improved use, with 75% (6/8) ONs identifying high call volumes due to inappropriate questions as a barrier to care. Sixty percent (18/30) of ONs reported having hospital-specific management plans for common issues would improve the care provided by the PSL. CONCLUSION: Despite high rates of satisfaction with the care provided by the PSL, our study identified several important areas for improvement which we feel warrant further investigation.

Evolving Role of Risk Tailored Therapy in Early Stage HER2-Positive Breast Cancer: A Canadian Perspective.

The advent of HER2-targeted therapies has led to an important shift in the management of HER2-positive early breast cancer. However, initial treatment approaches apply uniform treatment regimens to all patients, with significant treatment-related and financial toxicities for both the patient and the health care system. Recent data demonstrates that for many patients, the chemotherapy backbone, duration and nature (mono- versus dual-targeted therapy) of the HER2 blockade can be better targeted to an individual patient's risk of recurrence. We will provide a review of current data supporting risk tailored therapy in early stage HER2-positive breast cancer along with key completed and ongoing Canadian and international risk tailored trials. Neoadjuvant systemic therapy should now be considered for patients with clinical stage 2 disease, with greater use of non-anthracycline based chemotherapy regimens. Patients with residual disease following neoadjuvant therapy should be considered for escalated treatment with adjuvant T-DM1. Patients with stage I disease can often be managed with upfront surgery and evidence-based de-escalated adjuvant chemotherapy regimens. The modest benefit of 12- versus 6 months of adjuvant HER2 therapy and/or dual adjuvant HER2 therapy should be carefully weighed against the toxicities. All patients with HER2-positive breast cancer should be enrolled in ongoing risk tailored treatment trials whenever possible. Increasing data supports risk tailored therapy in early stage HER2-positive breast cancer in place of the routine application of aggressive and toxic systemic therapy regimens to all patients. While much progress has been made towards treatment de-escalation in appropriate patients, more is needed, as we highlight in this review. Indeed, Canadian-led clinical trials are helping to lead these efforts.

Using machine learning to predict individual patient toxicities from cancer treatments.

PURPOSE: Machine learning (ML) is a powerful tool for interrogating datasets and learning relationships between multiple variables. We utilized a ML model to identify those early breast cancer (EBC) patients at highest risk of developing severe vasomotor symptoms (VMS). METHODS: A gradient boosted decision model utilizing cross-sectional survey data from 360 EBC patients was created. Seventeen patient- and treatment-specific variables were considered in the model. The outcome variable was based on the Hot Flush Night Sweats (HFNS) Problem Rating Score, and individual scores were dichotomized around the median to indicate individuals with high and low problem scores. Model accuracy was assessed using the area under the receiver operating curve, and conditional partial dependence plots were constructed to illustrate relationships between variables and the outcome of interest. RESULTS: The model area under the ROC curve was 0.731 (SD 0.074). The most important variables in the model were as follows: the number of hot flashes per week, age, the prescription, or use of drug interventions to manage VMS, whether patients were asked about VMS in routine follow-up visits, and the presence or absence of changes to breast cancer treatments due to VMS. A threshold of 17 hot flashes per week was identified as being more predictive of severe VMS. Patients between the ages of 49 and 63 were more likely to report severe symptoms. CONCLUSION: Machine learning is a unique tool for predicting severe VMS. The use of ML to assess other treatment-related toxicities and their management requires further study.

VIVA1: a more invasive subclone of MDA-MB-134VI invasive lobular carcinoma cells with increased metastatic potential in xenograft models.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer. As few tools exist to study ILC metastasis, we isolated ILC cells with increased invasive properties to establish a spontaneously metastasising xenograft model. METHODS: MDA-MB-134VI ILC cells were placed in transwells for 7 days. Migrated cells were isolated and expanded to create the VIVA1 cell line. VIVA1 cells were compared to parental MDA-MB-134VI cells in vitro for ILC marker expression and relative proliferative and invasive ability. An intraductally injected orthotopic xenograft model was used to assess primary and metastatic tumour growth in vivo. RESULTS: Similar to MDA-MB-134VI, VIVA1 cells retained expression of oestrogen receptor (ER) and lacked expression of E-cadherin, however showed increased invasion in vitro. Following intraductal injection, VIVA1 and MDA-MB-134VI cells had similar primary tumour growth and survival kinetics. However, macrometastases were apparent in 7/10 VIVA1-injected animals. Cells from a primary orthotopic tumour (VIVA-LIG43) were isolated and showed similar proliferative rates but were also more invasive than parental cells. Upon re-injection intraductally, VIVA-LIG43 cells had more rapid tumour growth with similar metastatic incidence and location. CONCLUSIONS: We generated a new orthotopic spontaneously metastasising xenograft model for ER+ ILC amenable for the study of ILC metastasis.

Attitudes towards open-label versus placebo-control designs in oncology randomized trials: A survey of medical oncologists.

RATIONALE, AIMS AND OBJECTIVES: Randomized trials are considered the gold standard when assessing the efficacy of new therapeutic agents. In clinical situations where no standard of care therapy is approved, randomized trials usually compare experimental agents to either a placebo or an open-label nonintervention arm (i.e., best supportive care). We surveyed Canadian medical oncologists to understand their attitudes towards each design. METHODS: Members of the Canadian Association of Medical Oncologists were invited to participate in an anonymous online survey. Standardized case scenarios were used to determine participants' attitudes regarding the role of open-label versus placebo-controlled trials. RESULTS: A total of 322 medical oncologists and trainees were invited to participate and 86 responded (response rate 27%). Fifty-one (59%) believed that open-label trials are an acceptable alternative to placebo-controlled design when investigating a therapeutic agent in the adjuvant setting. Thirty-eight (49%) deemed it acceptable to compare the investigational agent to an open-label arm instead of a placebo to assess progression-free survival in the metastatic setting. Twenty-eight (38%) of respondents felt that open-label design was acceptable when assessing the quality of life endpoint. Most physicians were unsure whether the US Food and Drug Administration require a placebo-controlled arm in oncology trials. CONCLUSION: Canadian medical oncologists participating in this survey are divided in their opinions regarding the acceptability of an open-label design in randomized-controlled trials, where no standard therapy is approved. Clearer guidance from regulatory bodies on the adequacy of different trial designs is needed.

Vasomotor symptoms in early breast cancer-a "real world" exploration of the patient experience.

BACKGROUND: Despite the frequency of vasomotor symptoms (VMS) in patients with early breast cancer (EBC), their optimal management remains unknown. A patient survey was performed to determine perspectives on this important clinical challenge. METHODS: Patients with EBC experiencing VMS participated in an anonymous survey. Patients reported on the frequency and severity of VMS using the validated Hot Flush Rating Scale (HFRS) and ranked their most bothersome symptoms. Respondents were also asked to determine endpoints that defined effective treatment of VMS and report on the effectiveness of previously tried interventions. RESULTS: Responses were received from 373 patients, median age 56 years (range 23-83), who experienced an average of 5.0 hot flashes per day (SD 6.57). Patients reported the most bothersome symptoms to be feeling hot/sweating (155/316, 49%) and sleeping difficulties (86/316, 27%). Fifty-five percent (201/365) of patients would consider a treatment to be effective if it reduced night-time awakenings. While 68% of respondents were interested in trying interventions from their healthcare team to manage VMS, only 18% actually did so. Of the 137 patients who had tried an intervention for VMS, pharmacological treatments, exercise, and relaxation strategies were more likely to be effective, while therapies such as melatonin and black cohosh were deemed less effective. CONCLUSION: VMS are a common and bothersome problem for EBC patients, with a minority receiving interventions to manage these symptoms. Further research is needed to identify patient-centered strategies for managing these distressing symptoms.