Supplementary Tables 1-3, Supplementary Figures 1 and 2, Supplementary Data 1 and 2

Immune checkpoint inhibitor (ICI)-induced insulin-dependent diabetes mellitus (IDDM) is a rare but potentially fatal immune-related adverse event (irAE). In this multicentre retrospective cohort study, we describe the characteristics of ICI-induced IDDM in patients treated across five Canadian cancer centres, as well as their tumor response rates and survival. In 34 patients identified, 25 (74%) were male and 19 (56%) had melanoma. All patients received anti-programed death 1 (anti-PD1) or anti-programmed death ligand-1 (anti-PD-L1)-based therapy. From ICI initiation, median time to onset of IDDM was 2.4 months (95% CI 1.1–3.6). Patients treated with anti-PD1/PD-L1 in combination with an anti-cytotoxic T lymphocyte antigen 4 antibody developed IDDM earlier compared with patients on monotherapy (1.4 vs. 3.9 months, p = 0.05). Diabetic ketoacidosis occurred in 21 (62%) patients. Amongst 30 patients evaluable for response, 10 (33%) had a complete response and another 10 (33%) had a partial response. Median overall survival was not reached (95% CI NE; median follow-up 31.7 months). All patients remained insulin-dependent at the end of follow-up. We observed that ICI-induced IDDM is an irreversible irAE and may be associated with a high response rate and prolonged survival.

Purpose The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. Methods An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. Results Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. Conclusions Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.

Abstract Background: Preventive endocrine therapy (ET) has been proven extensively to decrease breast cancer (BC) risk by 50-65%. Despite this significant reduction, a small proportion of high risk women take ET, due to attitudes toward medications, inaccurate risk perception and drug side-effects. The addition of a polygenic risk score (PRS), comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)), to the standard risk calculator estimates, can be used to improve BC risk estimation. We previously reported on the influence of the PRS-adjusted BC risk estimates on the intent to use ET (Abstract, SABCS, 2019). Here we report on the influence of PRS-adjusted BC risk estimates on ET adherence at 1 and 2 year follow –up. We also report on ET side effects over this same time period. Methods: Women older than age 35 were eligible if they were deemed at high risk for BC by either a 5 year Gail Model risk of ≥3% or 10 year Tyrer-Cuzick risk (IBIS) of ≥5%. We excluded women with a personal history of BC or hereditary BC syndromes. At baseline, participants were counseled on their BC risk using standard risk calculators: Gail and IBIS risk scores (5 yr, 10 yr, & lifetime) and ET options were discussed, including benefits and risks. Blood samples were obtained and genotyped for 77 SNPs, and an updated BC -PRS risk report was shared with study participants that reflected the IBIS and Gail risk predictions for 5 yr, 10 yr, & lifetime BC risk with and without the PRS. A baseline self-reported questionnaire assessed understanding of BC risk and decision to take ET. Follow-up questionnaires at 1 and 2 years assessed self-reported ET adherence and ET side effects (vasomotor symptoms, vaginal symptoms, sexual dysfunction, weight gain, GI symptoms, headaches, breast sensitivity, mood changes, and joint pain). Adherence to ET at 1 and 2 year follow-up was stratified by three categories of lifetime PRS-BC risk: 0-20%; 20-40%; 40-100%. Results: 151 women at Mayo Clinic Rochester and CancerCare Manitoba were enrolled in the study from 2016 to 2017. Of the 149 participants with evaluable data at 1 and 2 year follow-up, 57 (38%) started on ET therapy, all within 1 year of the baseline visit; 43 (29%) were taking ET at 1 year and 33 (22%) were taking ET at 2 year follow-up, representing a discontinuation rate of 26% at 1 year and 42% at 2 year follow-up. Adherence to ET use at 1 year and 2 year follow-ups correlated significantly with the category of PRS-BC risk estimation: at 1 year follow up, 17% of those in the lowest PRS-IBIS risk category, 23% in the middle risk category and 50% of those in the highest risk category were taking ET (p=0.001). At 2 year follow up, 12% of those in the lowest PRS-IBIS risk category, 18% in the middle risk category and 38% of those in the highest risk category were taking ET (p=0.008). At 1 year follow up, participants taking ET reported significantly more bothersome symptoms of vaginal itching (p=0.010), weight gain (p=0.015) and joint pain (p=0.044), compared with those not on ET. There was a trend towards increased irritability and mood swings on those taking ET (p=0.059). At year 2 there was no significant difference in side effects between those taking and not taking ET. Conclusion: Adherence to ET in a population of women at high risk for BC decreased overtime and strongly correlated with the level of risk, with 38% of those at highest risk of breast cancer taking ET at 2 year follow up. Side effects of vaginal itching, weight gain and body aches were more common on those taking ET versus not taking ET at the 1 year follow-up, but did not differ at 2 year follow-up, possibly due to the fact that those with the most bothersome symptoms have discontinued ET by the 2 year follow up. Citation Format: Daniela Stan, Julian Kim, Daniel Schaid, Erin Carlson, Andrew Cooke, Christina A. Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Amy Degnim, Fergus Couch, Celine Vachon, Sandhya Pruthi. Influence of a breast cancer polygenic risk score on adherence to preventive endocrine therapy in high risk women at 1 and 2 year follow-up: The genetic risk estimate (GENRE) trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-02.

Background: Globally there is a move to adopt competency-based medical education (CBME) at all levels of the medical training system. Implementation of a complex intervention such as CBME represents a marked paradigm shift involving multiple stakeholders. Methods: This article aims to share tips, based on review of the available literature and the authors’ experiences, that may help educators implementing CBME to more easily navigate this major undertaking and avoid “black ice” pitfalls that educators may encounter. Results: Careful planning prior to, during and post implementation will help programs transition successfully to CBME. Involvement of key stakeholders, such as trainees, teaching faculty, residency training committee members, and the program administrator, prior to and throughout implementation of CBME is critical. Careful and selective choice of key design elements including Entrustable Professional Activities, assessments and appropriate use of direct observation will enhance successful uptake of CBME. Pilot testing may help engage faculty and learners and identify logistical issues that may hinder implementation. Academic advisors, use of curriculum maps, and identifying and leveraging local resources may help facilitate implementation. Planned evaluation of CBME is important to ensure choices made during the design and implementation of CBME result in the desired outcomes. Conclusion: Although the transition to CBME is challenging, successful implementation can be facilitated by careful design and strategic planning.

AbstractEndocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer–Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled [median (range) age, 56.1 (36.0–76.4 years)]. Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed.Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.

Abstract Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine therapy (ET) and yet drug uptake and adherence in this setting is suboptimal even among high risk women. A Polygenic Risk Score (PRS) comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)) can provide a personalized risk assessment and potentially influence ET adherence. We assessed ET adherence at 1 year comparing women whose risk estimate increased due to PRS versus women whose risk estimate decreased due to PRS. The effect of ET use on quality of life (hot flashes, night sweats, vaginal dryness, weight gain, joint pain) was evaluated. Methods: Eligible women required either a 5 year Gail Model risk of ≥3% or 10 year IBIS ( International Breast Intervention Study or Tyrer-Cuzick model) of ≥5%. Women with a history of breast cancer (BC) or hereditary BC syndrome were excluded. High risk women were counseled at baseline using their Gail and IBIS risk scores and ET options were discussed including benefits and risks. Participants completed a self-reported questionnaire at baseline to assess their understanding of breast cancer risk and decision to take preventive ET. Blood samples were obtained and genotyped for 77 SNPs, and the odds ratio from the SNPs were used to modify the IBIS and Gail risk estimates. The BC -PRS risk estimate information was shared with study participants that reflected the IBIS and Gail risk estimates for 5 year, 10 year, & lifetime BC risk with and without the PRS. Follow up questionnaires at year 1 were administered to assess drug adherence and ET usage on quality of life. Results: 151 women were enrolled at Mayo Clinic Rochester and CancerCare Manitoba from 2016 to 2017. The median age was 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian and 64.7% had>1 family member with BC. Median 5yr, 10yr, & lifetime IBIS- PRS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). At year 1 (n=112 women) 46 % of those with an increase in risk when considering the BC-PRS score and 16 % with a decrease in risk were taking ET ( p< 0.001). Types of ET taken: tamoxifen-18, raloxifene- 3, exemestane -14 and missing-1. Women taking ET reported weight gain ( 19.4% vs 6.7%, p=0.04) and more joint pain ( 27.8 % vs 12%, p=0.04) when compared to women not taking ET. Conclusion: In high risk women, BC-PRS risk estimates in addition to standard BC risk calculators had a significant impact on preventive ET adherence. ET use was associated with weight gain and joint pain. Citation Format: Sandhya Pruthi, Julian O Kim, Daniel Schaid, Andrew Cooke, Christina Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Fergus Couch, Celine Vachon. Impact of the breast cancer polygenic risk score on preventive endocrine therapy adherence and endocrine therapy usage on quality of life - The Genetic Risk Estimate (GENRE) trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-03.

1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very few at-risk women choose to take them. A woman’s perceived BC risk correlates with uptake of ET. A PRS comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP) improves the accuracy of risk prediction for BC. We examined the impact of the addition of individualized PRS BC risk prediction to standard risk calculator estimates on intent to take BC prevention medication. Methods: Eligible women had ≥5% 10 yr BC Tyrer-Cuzick risk (IBIS) or 5 year Gail score ≥3%, with no history of BC or hereditary BC syndrome. Standard BC risk estimates (IBIS or Gail) were incorporated into the counselling on BC preventive ET. A self-reported questionnaire at baseline quantified intention to take ET and explored factors associated with this decision. Blood samples were obtained and genotyped for 77 SNPs, individualized PRS were calculated then incorporated into IBIS and Gail predictions for 5 yr, 10 yr, & lifetime BC risk. At a second visit, PRS risk & prevention recommendations were revisited. Post visit questionnaires assessed change in intent to take ET. Multivariable linear regression was performed to assess impact of baseline variables on change in intent to take medication. Results: From 2016 to 2017, 151 women in Canada & USA were enrolled, median age: 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian. Median 5yr, 10yr, & lifetime IBIS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). PRS increased BC risk estimates in 84 (55.6%) and reduced BC risk estimates in 67 (44%) women. After PRS risk counselling, intention to take ET significantly changed (p<0.001): 41.9% of those with increased PRS were more inclined, and 46.7% of women with decreased PRS were less inclined to take ET. On multivariable regression, increase in PRS (p<0.0001) and less concern about ET side effects (p<0.0001) were associated with greater intent to take ET. Conclusions: In high risk women, PRS significantly changed BC risk estimates & intent to take preventive ET. Further assessments of the impact of PRS scores on compliance with ET are warranted. Clinical trial information: NCT02517593.

PURPOSE Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

Therapy for breast cancer involves a complex interplay of three main treatment modalities: surgery, systemic therapy, and radiation therapy. The Canadian Consortium for Locally Advanced Breast Cancer (LABC) was established with the goal to convene a strong multidisciplinary team of breast oncology clinicians and scientists who are dedicated to the advancement of LABC research and treatment, with a vision to drive progress through increased collaboration across disciplines and throughout Canada. The most recent meeting in May 2017 highlighted the latest evidence and literature about the optimal use of neoadjuvant systemic therapy in breast cancer. There is a need for increased clinical and scientific collaboration and the development of guidelines for the use of emerging treatment strategies. The interactive meeting sessions fostered unique opportunities for academic debate and nurtured collaboration between the attendees.

e12000 Background: The incidence of early-stage breast cancers has increased dramatically over the past decades. Treatment decisions for patients with stage I breast cancers are challenging, as there are significant variations in outcomes based on biologic subtypes. The objectives were to describe the distribution, molecular phenotypes, management, and long-term outcomes of women with early-stage breast cancer (T1mic/T1a/T1b N0 M0) in Manitoba from 2006-2011. Methods: Using the Manitoba Cancer Registry, we created a retrospective cohort of patients with primary breast cancer of ≤1.0 cm, diagnosed between 2006 and 2011. Data included patient demographics, tumour size, treatment modalities (surgery, radiotherapy, chemotherapy and trastuzumab), estrogen-receptor (ER) and progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. Node-positive cancers were excluded. Patient outcomes were evaluated, including rates of recurrence and overall survival using univariate and multivariable models. Kaplan-Meier curves and cumulative incidence curves were used to illustrate overall survival and recurrence, respectively. Results: Our study included 733 women. Mean age at diagnosis was 62. ER/PR positivity and HER2 positivity (HER2+) were 84% and 8.9%, respectively. Tumours were: T1mic in 14.0%, T1a in 19.1%, and T1b in 66.9%. 98% of patients had surgery, 60% had adjuvant radiation, 3.8% received trastuzumab, and 11% received chemotherapy. The adjusted hazard ratio (HR) for disease recurrence for patients with HER2+ versus HER2- status was 4.31 (95% CI, 2.18 to 8.50; P = 0.0001), and the HR for overall survival was 1.63 (95% CI, 0.72 to 3.67; P = 0.2402). The HR for disease recurrence in HER2+ patients receiving trastuzumab versus HER2+ patients who did not receive trastuzumab was 1.92 (95% CI, 0.61 to 5.97; P = 0.2621). Conclusions: HER2-positivity appears to be an important risk factor for recurrence in small, early-stage breast cancers. In our cohort, trastuzumab did not appear to reduce the risk of recurrence compared to those who did not receive it. This may be due to limited power and selection bias, in which patients with higher risk cancers received trastuzumab.

Background: Data on the comparative efficacy of fulvestrant and other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified.Methods: We searched the literature from inception to May 2015, using MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials (RCTs) that compared fulvestrant containing arm to either tamoxifen or an aromatase inhibitors (AI) and presented results for subgroup analyses as Hazard Ratios (HR) for Time to Progression (TTP) or Progression Free Survival (PFS). Subgroup analyses reported in at least two RCTs were included. Data were then weighted using generic inverse variance approach and pooled in meta-analysis using RevMan 5.3 software. Difference between subgroups was tested with chit statistics.Results: Analysis included 4 RCTs comparing fulvestrant-based therapy to AI alone and comprising 2382 patients (1190 on fulvestrant and 1192 on control arms). TTP/PFS was the primary endpoint in all included studies. Four sub-groups fulfilled our criteria. Fulvestrant was associated with greater benefit in patients with visceral metastasis (HR 0.85 vs 1.02 for no visceral disease, p for difference = 0.05) and in those patients with a time to recurrence >5 years (HR 0.80 vs 1.09 for recurrence <= 5 years, p for difference = 0.02). There was no apparent difference in benefit based on age >65 years (HR 0.86 vs 0.96, p for difference = 0.32) or HER2/neu status (HR 0.36 vs 0.92, p for difference = 0.09).Conclusion: Patients with advanced breast cancer with visceral involvement and longer time from diagnosis to recurrence had significantly better TTP/PFS with the use of fulvestrant. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice. (C) 2016 Elsevier Ltd. All rights reserved.

Abstract OBJECTIVES: The objectives of this study were to describe the distribution, management, and outcomes of women with early-stage breast cancer in Manitoba during the period from 1995-2011. Specifically, we looked at tumours 1cm or smaller in size (T1mic/T1a/T1b) across the spectrum of molecular phenotypes: estrogen-receptor (ER) status, progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2) status. This is the first study to evaluate these objectives in Manitoba, and will contribute significantly to the limited data of long-term outcomes for smaller-sized breast tumours. METHODS: Using the Manitoba Cancer Registry, we created a retrospective cohort of all patients with primary breast cancer of 1.0 cm or less, between 1995 and 2011. Women with previous or synchronous contralateral breast cancers were excluded. Data included patient demographics, diagnostic procedure, tumour size, nodal disease, treatment modalities (surgery, radiotherapy, hormone therapy, and chemotherapy), ER status, PR status, and HER2 status. Linkage to the Manitoba Health Drug Program Information Network (DPIN) database allowed capture of all hormonal therapies. Patient outcomes were evaluated, including risk of recurrence, overall survival and relative survival. Risk of recurrence was illustrated using cumulative incidence of recurrence, accounting for the competing risk of death. Kaplan-Meier curves were used to illustrate overall survival. The relative survival estimate was used to estimate the probability of surviving from breast cancer while controlling for differences in mortality due to other causes. RESULTS: Our study captured 2,341 women. Mean age at diagnosis was 62. ER+, PR+, and HER2+ status were 71% (11% unknown), 61.6% (11% unknown), and 8.6% (31% unknown), respectively. Clinically, 78% were Stage I disease, and by tumour size overall: T1mic 11.5%, T1a 18.9%, and T1b 69.7%. Ninety-eight percent had primary surgery, 58% had primary radiation, 48% received hormone therapy, and 16% received chemotherapy. At last follow-up, 21% of all patients were deceased. Relative survival estimates revealed that the survival of the overall cohort was not different than the general population, when comparing based on age groupings for Manitoban females. Recurrence occurred in 6.6% (156) of all cases. ER+, PR+, and HER2+ status were 63% (4% unknown), 58% (4% unknown), and 48% (5% unknown), respectively. By staging, 65% were Stage I disease and by tumour size 60% were T1b. Overall, 64% of recurrences were node-negative. For the HER2+, node-negative subpopulation at diagnosis: 21% of the T1mic group recurred, 41% of T1a recurred, and 19% of T1b recurred. In all recurrences, 39% of patients were deceased at last follow-up. CONCLUSIONS: Small, early-stage breast cancers are common and a significant proportion of patients recur. HER2-positivity appears to be an important risk factor for recurrence and may independently warrant treatment with trastuzumab, regardless of primary tumour size. Citation Format: Aly-Khan Lalani, Katherine Fradette, Rashid Ahmed, Debjani Grenier, Marshall Pitz. Outcomes of women with small, early-stage breast cancer in Manitoba from 1995-2011 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-13.

Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure, congenital malformations and a propensity for developing malignancies at an early age. The underlying genetic defect in FA creates a state of cellular hypersensitivity to many traditional chemotherapy agents, making the treatment of malignancies in this population particularly challenging.

155 Background: The objectives of this implementation study were to 1) identify and address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice, and 2) follow patients during the first few days following receipt of the consultation recording to document, from the patient’s perspective, the benefits realized from listening to the recording. Methods: Nine medical and 9 radiation oncologists from cancer centers in three Canadian cities (Calgary, Vancouver, Winnipeg) recorded their primary treatment consultations for 228 patients newly diagnosed with prostate or breast cancer. The Digital Recording Use Semi-Structured Interview (DRUSSI) was conducted at two days post-consultation and at 1-week post-consultation. Each oncologist was given a feedback letter summarizing the consultation recording benefits reported by their patients. Results: Sixty-nine percent of patients listened to at least a portion of the recording within the first week following the consultation. Consultation recording favourableness ratings were high: 93.6% rated the intervention between 75–100 on a 100-point scale. Four main areas of benefit were reported: 1) Anxiety reduction; 2) Enhanced retention of information; 3) Better informed decision making; and 4) Improved communication with family members. Eight fundamental components of successful transfer and uptake of consultation recording practice were identified. Conclusions: Implementation research and additional randomized trials are needed to facilitate the transfer and uptake of consultation recording use so that far more patients and significant others may realize the associated benefits.

To determine if higher bone mineral density (BMD) is a risk factor for breast cancer in women age 50 years and older. 37,860 women ≥50-year old with no previous breast cancer diagnosis had baseline BMD assessment between January 1999 and December 2007. Cox proportional hazards models were created for time to a new breast cancer as a function of lumbar spine or femoral neck BMD quartile (1st = lowest as reference) with adjustment for relevant covariates. A secondary analysis was performed to look for an association with estrogen receptor-positive (ER-positive) breast cancers. 794 invasive and in situ breast cancers (484 ER-positive) occurred with a median follow up of 5.4 years. Increased breast cancer risk was seen for the 3rd and 4th quartiles of lumbar spine BMD with hazard ratios (HRs) of 1.26 (95% CI, 1.01–1.58) and 1.45 (95% CI, 1.16–1.81), respectively and for the 3rd quartile of femoral neck BMD with a HR of 1.33 (95% CI, 1.07–1.64). A test for linear trend showed that lumbar spine BMD (P < 0.001) and femoral neck BMD (P = 0.04) were associated with increased risk. Higher lumbar spine BMD was also associated with increased risk of ER-positive breast cancer with HR of 1.45 (95% CI, 1.08–1.94), and 1.68 (95% CI, 1.24–2.27) for women in the 2nd and 4th quartiles, respectively. A test for linear trend showed lumbar spine BMD was associated with increasing risk of ER-positive breast cancer (P = 0.003). Increased ER-positive breast cancer risk was seen for the 3rd quartile of femoral neck BMD with a HR of 1.43 (95% CI, 1.08–1.89). Higher lumbar spine and femoral neck BMD are associated with higher risk of breast cancer in women ≥50-year old. Lumbar spine and femoral neck BMD are associated with increased risk of ER-positive breast cancer.

OBJECTIVES:The aim of this study was to evaluate whether cardiac biomarkers, tissue velocity (TVI) and strain imaging, and cardiac magnetic resonance imaging can predict early left ventricular (LV) dysfunction in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting. BACKGROUND:Early indexes of LV systolic dysfunction with noninvasive cardiac imaging would be useful for addressing the cardiac safety profile of trastuzumab, potentially avoiding the detrimental effects of heart failure. METHODS:We used cardiac biomarkers, TVI and strain imaging, and cardiac magnetic resonance imaging to detect pre-clinical changes in LV systolic function, before conventional changes in left ventricular ejection fraction (LVEF) in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting. RESULTS:Of 42 patients (mean age 47 ± 9 years) prospectively followed between 2007 and 2009, 10 (25%) developed trastuzumab-mediated cardiomyopathy (CM). Troponin T, C-reactive protein, and brain natriuretic peptide did not change over time. Within 3 months of adjuvant therapy with trastuzumab, there was a significant difference in the lateral S' between the normal cohort and the CM group (9.1 ± 1.6 cm/s and 6.4 ± 0.6 cm/s, respectively, p < 0.05). Similarly, the peak global longitudinal and radial strain decreased as early as 3 months in the trastuzumab-mediated cardiotoxicity group. As compared with both global longitudinal and radial strain, only S' was able to identify all 10 patients who developed trastuzumab-mediated CM. The LVEF subsequently decreased at 6 months of follow-up in all 10 patients, necessitating discontinuation of the drug. All 10 patients demonstrated delayed enhancement of the lateral wall of the LV within the mid-myocardial portion, consistent with trastuzumab-induced CM. CONCLUSIONS:Both TVI and strain imaging were able to detect pre-clinical changes in LV systolic function, before conventional changes in LVEF, in patients receiving trastuzumab in the adjuvant setting.

BACKGROUND:The time period from diagnosis to the end of treatment is challenging for newly diagnosed cancer patients. Patients have a substantial need for information, decision aids, and psychosocial support. Recordings of initial oncology consultations improve information recall, reduce anxiety, enhance patient satisfaction with communication, and increase patients' perceptions that the essential aspects of their disease and treatment have been addressed during the consultation. Despite the research evidence supporting the provision of consultation recordings, uptake of this intervention into oncology practice has been slow. The primary aim of this project is to conduct an implementation study to explicate the contextual factors, including use of evidence, that facilitate and impede the transfer and uptake of consultation-recording use in a sample of patients newly diagnosed with breast or prostate cancer.METHODS:Sixteen oncologists from cancer centres in three Canadian cities will participate in this three-phase study. The preimplementation phase will be used to identify and address those factors that are fundamental to facilitating the smooth adoption and delivery of the intervention during the implementation phase. During the implementation phase, breast and prostate cancer patients will receive a recording of their initial oncology consultation to take home. Patient interviews will be conducted in the days following the consultation to gather feedback on the benefits of the intervention. Patients will complete the Digital Recording Use Semi-Structured Interview (DRUSSI) and be invited to participate in focus groups in which their experiences with the consultation recording will be explored. Oncologists will receive a summary letter detailing the benefits voiced by their patients. The postimplementation phase includes a conceptual framework development meeting and a seven-point dissemination strategy.DISCUSSION:Consultation recording has been used in oncology, family medicine, and other medicine specialties, and despite affirming evidence and probable applications to a large number of diseases and a variety of clinical contexts, clinical adoption of this intervention has been slow. The proposed study findings will advance our conceptual knowledge of the ways to enhance uptake of consultation recordings in oncology.