Gynecologic Symptoms among Hormone Receptor-Positive Breast Cancer Patients on Oral Endocrine Therapy: A Cross-Sectional Study.

Endocrine therapy (ET) for hormone receptor-positive (HR+) breast cancer can contribute to gynecologic symptoms (GS) that impact vaginal health, sexual function, and quality of life (QoL). A cross-sectional study was conducted at St. Michael's Hospital in Toronto, Canada between July 2017 and June 2018 to examine the occurrence and frequency of GS among HR+ breast cancer patients on ET, patient-provider communication, female sexual dysfunction (FSD), and QoL. A Treatment Experience questionnaire was developed for this study and the Female Sexual Function Index (FSFI) and Menopause-Specific Quality of Life questionnaire (MENQOL) were also administered. Of 151 patients surveyed, 77 (51.0%) were on tamoxifen and 74 (49.0%) on an aromatase inhibitor. Most patients (84.1%, 95% confidence interval [CI] 77.3% to 89.5%) experienced at least one GS "all the time" or "often", or one or more infections, in the past year. Only 44 (31.9%) patients reported that their oncologist had ever previously asked them about experiencing GS. The prevalence of FSD was 61.2% (95% CI 46.2% to 74.8%) among 49 sexually active patients that completed the FSFI. Symptoms captured in the MENQOL's vasomotor domain were deemed most bothersome. Side effect management and patient-provider communication should be prioritized to optimize GS, vaginal health, and sexual function of ET users.

A Multidisciplinary Approach to Implement Personalized Breast Cancer Treatment and Care Plans.

Implementation of survivorship care plans remain a challenge. This quality improvement initiative aims to integrate personalized treatment plans (PTP) and care plans (PCP) into the existing workflow for breast cancer (BC) patients. Methods: Phase 1 was to identify multidisciplinary team members to generate and deliver PTP and PCP. Concurrently, Phase 2 was to deliver PTP and PCP to newly diagnosed invasive BC patients at chemotherapy initiation and completion, respectively. Iterative plan, do, study, act (PDSA) cycles were applied to refine the process. The proportion of information completed for PTP and PCP generation and its delivery by the care team were measured. Patient and provider satisfaction were also assessed. Implementation Process and Results: The care transfer facilitator (CTF) was identified to complete and deliver PTP, and their data entry increased from 0% to 76%, 80%, 92% consecutively during the last 4 PDSA cycles. PTP and PCP were provided to 85% of eligible BC patients. Patients agreed that PTP helped them to actively participate in their care (88%) and communicate with the oncology care team (86%). Primary care physicians agreed that PTP and PCP had the information needed to "stay in the loop" (80%), and oncologists agreed they should be incorporated into oncology clinics (100%). Conclusions: Integrating PTP and PCP generation and delivery into existing workflow has led to an increase in uptake, sustainability and provider buy-in. With limited resources, it remains difficult to find care team members to complete the forms. A dedicated personnel or survivorship clinic is required to successfully implement PTP and PCP as the standard of care.

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study.

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Reclassification of breast cancer: Towards improved diagnosis and outcome.

BACKGROUND: The subtyping of breast cancer based on features of tumour biology such as hormonal receptor and HER2 status has led to increasingly patient-specific treatment and thus improved outcomes. However, such subgroups may not be sufficiently informed to best predict outcome and/or treatment response. The incorporation of multi-modal data may identify unexpected and actionable subgroups to enhance disease understanding and improve outcomes. METHODS: This retrospective cross-sectional study used the cancer registry Surveillance, Epidemiology and End Results (SEER), which represents 28% of the U.S. population. We included adult female patients diagnosed with breast cancer in 2010. Latent class analysis (LCA), a data-driven technique, was used to identify clinically homogeneous subgroups ("endophenotypes") of breast cancer from receptor status (hormonal receptor and HER2), clinical, and demographic data and each subgroup was explored using Bayesian networks. RESULTS: Included were 44,346 patients, 1257 (3%) of whom had distant organ metastases at diagnosis. Four endophenotypes were identified with LCA: 1) "Favourable biology" had entirely local disease with favourable biology, 2) "HGHR-" had the highest incidence of HR- receptor status and highest grade but few metastases and relatively good outcomes, 3) "HR+ bone" had isolated bone metastases and uniform receptor status (HR+/HER2-), and 4) "Distant organ spread" had high metastatic burden and poor survival. Bayesian networks revealed clinically intuitive interactions between patient and disease features. CONCLUSIONS: We have identified four distinct subgroups of breast cancer using LCA, including one unexpected group with good outcomes despite having the highest average histologic grade and rate of HR- tumours. Deeper understanding of subgroup characteristics can allow us to 1) identify actionable group properties relating to disease biology and patient features and 2) develop group-specific diagnostics and treatments.

Using Implementation Science to Promote the Use of the G8 Screening Tool in Geriatric Oncology.

OBJECTIVES: Evidence supports the integration of geriatric assessment in the care of older adults with cancer. The G8 screening tool is a validated instrument to target a geriatric assessment. Use of the G8 tool in clinical practice, however, is suboptimal. We systematically analyzed the barriers and facilitators to G8 tool use in oncology clinics and selected interventions tailored to the local context to enhance its uptake. DESIGN: This qualitative study used semistructured interviews and site observations. SETTING: St. Michael's Hospital, Toronto, Canada. PARTICIPANTS: Ten participants including G8 tool adopters and stakeholders at St. Michael's Hospital were interviewed. MEASUREMENTS: An interview guide based on the Theoretical Domains Framework (TDF) was developed to identify beliefs about G8 tool use. Barriers and facilitators to G8 tool use were mapped to the TDF domains and corresponding intervention functions from the Capability, Opportunity, Motivation, and Behavior model. Evidence-based implementation strategies were selected from two databases. RESULTS: Key TDF domains influencing G8 tool use behavior were social/professional role, goals, beliefs about consequences, and social influences. The behavior change domains were mapped to four mechanisms of change: persuasion (conduct local consensus discussions), modeling (identify and prepare a champion), education (distribute educational materials), and enablement (use materials to prepare patients to be active participants in understanding the evidence behind the G8 tool and answering questions accurately). CONCLUSION: This study identified barriers to G8 tool use. Local consensus discussions, identifying and preparing a champion, using educational materials, and preparing patients to be active participants may be implementation strategies to improve G8 tool use. J Am Geriatr Soc 67:898-904, 2019.

Serial Measurements of Left Ventricular Systolic and Diastolic Function by Cardiac Magnetic Resonance Imaging in Patients with Early Stage Breast Cancer on Trastuzumab.

Our aim was to evaluate the temporal changes in left ventricular (LV) diastolic filling in relation to other LV parameters using cardiac MRI (CMR) in patients with HER2 positive breast cancer receiving trastuzumab therapy. Fourty-one women with early stage HER2+ breast cancer underwent serial CMR (baseline, 6, 12, and 18 months) after initiation of trastuzumab therapy. A single, blinded observer measured LV parameters on de-identified CMRs in random order. Linear mixed models were used to investigate temporal changes. Compared to baseline, there were significant decreases in systolic function as measured by both left ventricular ejection fraction (LVEF) (p <0.001 at 6 and 12 months) and peak ejection rate corrected for end-diastolic volume (PER/LVEDV) (p = 0.008 at 6 months, p = 0.01 at 12 months). However, these differences were no longer significant at 18 months. In contrast, significant reductions in diastolic function as measured by LV peak filling rate corrected for end-diastolic volume (PFR/LVEDV) were observed at 6 months (p = 0.012), 12 months (p = 0.031), and up to 18 months (p = 0.034). There were no significant temporal changes in the time to peak filling rate corrected for cardiac cycle (TPF/RR). The reduction in PFR/LVEDV at 18 months was no longer significant when corrected for heart rate. In conclusion, there were significant subclinical deleterious effects on both LV systolic and diastolic function among patients receiving trastuzumab. While there was recovery in LV systolic function after therapy cessation at 18 months, reduction in PFR/LVEDV appeared to persist. Thus, diastolic dysfunction may serve as a marker of trastuzumab-induced cardiotoxicity that needs to be confirmed in a larger study.

Myocardial strain imaging by cardiac magnetic resonance for detection of subclinical myocardial dysfunction in breast cancer patients receiving trastuzumab and chemotherapy.

BACKGROUND: Our objectives were to evaluate the temporal changes in CMR-based strain imaging, and examine their relationship with left ventricular ejection fraction (LVEF), in patients treated with trastuzumab. PATIENTS AND METHODS: In this prospective longitudinal observational study, 41 women with HER2+ breast cancer treated with chemotherapy underwent serial CMR (baseline, 6, 12, and 18 months) after initiation of trastuzumab (treatment duration 12 months). LVEF and LV strain (global longitudinal[GLS] and circumferential[GCS]) measurements were independently measured by 2 blinded readers. RESULTS: Of the 41 patients, 56% received anthracycline-based chemotherapy. Compared to baseline (60.4%, 95%CI 59.2-61.7%), there was a small but significant reduction in LVEF at 6 months (58.4%, 95%CI 56.7-60.0%, p = 0.034) and 12 months (57.9%, 95%CI 56.4-59.7%, p = 0.012), but not at 18 months (60.2%, 95%CI 58.2-62.2%, p = 0.93). Similarly, compared to baseline, GLS and GCS decreased significantly at 6 months (p = 0.024 and < 0.001, respectively) and 12 months (p = 0.002 and < 0.001, respectively) with an increase in LV end-diastolic volume, but not at 18 months. There were significant correlations between the temporal (6 month-baseline) changes in LVEF, and all global strain measurements (Pearson's r = -0.60 and r = -0.75 for GLS and GCS, respectively, all p < 0.001). CONCLUSION: There was a significant reduction in LV strain during trastuzumab treatment, which correlated with a concurrent subtle decline in LVEF and was associated with an increase in LV end-diastolic volume. LV strain assessment by CMR may be a promising method to monitor for subclinical myocardial dysfunction in breast cancer patients receiving chemotherapy. Future studies are needed to determine its prognostic and therapeutic implications.

Web-based Oncology Educational Tool for Medical Trainees on Oncology Rotation-Results of a Pilot Study.

Oncology education for post-graduate medical trainees is mostly clinic-based with didactic lectures. However, a 3-4-week rotation lacks full exposure to the vast field of oncology, resulting in an educational gap. We felt there is a need for a standard curriculum to educate trainees on common oncology topics and encourage self-directed learning. This study aims to improve knowledge of oncology in trainees through the use of an oncology educational tool (consisting of a handbook and website) that we developed and evaluated. Fifty-three post-graduate trainees (years 1, 2, and 3) consented to participate at the start of their oncology rotation. In phase I, four participants took part in a usability evaluation of the tool. In phase II, 39 trainees underwent a knowledge assessment with use of the tool. Baseline and post-intervention test results were compared using paired t tests. In the qualitative study (phase III), 10 trainees provided feedback on the updated tool and overall rotation experience. Issues identified from phase I were addressed prior to subsequent phases. Phase II analysis of complete sets of data found the mean post-intervention scores (9.44/10) were significantly higher (p < 0.001) than the mean baseline scores (7.47/10). In the qualitative study, feedback strongly supported the integration of the tool for improving knowledge of trainees. To our knowledge, this is the first study to show that an oncology educational tool for medical trainees improves oncology knowledge by providing a standard curriculum. Future work involves evaluating this tool to determine if effects are from the education tool or rotation experience.

Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study.

BACKGROUND: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab. METHODS: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters. RESULTS: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17). CONCLUSION: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancer--results from NCIC CTG/AGITG CO.17.

PURPOSE: Cetuximab improves survival in patients with K-ras wild-type advanced colorectal cancer. We examined the predictive and prognostic significance of additional biomarkers in this setting, in particular BRAF, PIK3CA, and PTEN. EXPERIMENTAL DESIGN: Available colorectal tumor samples were analyzed from the CO.17 study. BRAF mutations were identified in tumor-derived DNA by direct sequencing and PIK3CA mutations were identified using a high-resolution melting screen with confirmation by sequencing. PTEN expression by immunohistochemistry (IHC) was performed on tissue microarrays. For each biomarker, prognostic and predictive effects were examined using a Cox model with tests for treatment-biomarker interaction. RESULTS: A total of 572 patients with pretreated colorectal cancer were randomly assigned to receive cetuximab or best supportive care (BSC). Of 401 patients assessed for BRAF status, 13 (3.2%) had mutations. Of 407 patients assessed for PIK3CA status, 61 (15%) had mutations. Of 205 patients assessed for PTEN, 148 (72%) were negative for IHC expression. None of BRAF, PIK3CA, or PTEN was prognostic for overall or progression-free survival in the BSC arm. None was predictive of benefit from cetuximab, either in the whole study population or the K-ras wild-type subset. In the K-ras wild-type subgroup, the overall survival adjusted HR according to BRAF mutation status was 1.39 (interaction P = 0.69), PIK3CA mutation status HR = 0.79 (interaction P = 0.63), and PTEN expression HR = 0.75 (interaction P = 0.61). CONCLUSIONS: In chemotherapy-refractory colorectal cancer, neither PIK3CA mutation status nor PTEN expression were prognostic, nor were they predictive of benefit from cetuximab. Evaluation of predictive significance of BRAF mutations requires a larger sample size.

Designing a multifaceted survivorship care plan to meet the information and communication needs of breast cancer patients and their family physicians: results of a qualitative pilot study.

BACKGROUND: Following the completion of treatment and as they enter the follow-up phase, breast cancer patients (BCPs) often recount feeling 'lost in transition', and are left with many questions concerning how their ongoing care and monitoring for recurrence will be managed. Family physicians (FPs) also frequently report feeling ill-equipped to provide follow-up care to BCPs. In this three-phase qualitative pilot study we designed, implemented and evaluated a multi-faceted survivorship care plan (SCP) to address the information needs of BCPs at our facility and of their FPs. METHODS: In Phase 1 focus groups and individual interviews were conducted with 35 participants from three stakeholder groups (BCPs, FPs and oncology specialist health care providers (OHCPs)), to identify specific information needs. An SCP was then designed based on these findings, consisting of both web-based and paper-based tools (Phase 2). For Phase 3, both sets of tools were subsequently evaluated via focus groups and interviews with 26 participants. Interviews and focus groups were audio taped, transcribed and content analysed for emergent themes and patterns. RESULTS: In Phase 1 patients commented that web-based, paper-based and human resources components were desirable in any SCP. Patients did not focus exclusively on the post-treatment period, but instead spoke of evolving needs throughout their cancer journey. FPs indicated that any tools to support them must distill important information in a user-friendly format. In Phase 2, a pilot SCP was subsequently designed, consisting of both web-based and paper-based materials tailored specifically to the needs of BCPs as well as FPs. During Phase 3 (evaluation) BCPs indicated that the SCP was effective at addressing many of their needs, and offered suggestions for future improvements. Both patients and FPs found the pilot SCP to be an improvement from the previous standard of care. Patients perceived the quality of the BCP-FP relationship as integral to their comfort with FPs assuming follow-up responsibilities. CONCLUSIONS: This pilot multi-component SCP shows promise in addressing the information needs of BCPs and the FPs who care for them. Next steps include refinement of the different SCP components, further evaluation (including usability testing), and planning for more extensive implementation.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase guideline adherence.

Multicenter, randomized, cross-over clinical trial of venlafaxine versus gabapentin for the management of hot flashes in breast cancer survivors.

PURPOSE: Nonhormonal pharmacologic interventions are recommended for the treatment of hot flashes in breast cancer survivors. Antidepressants and gabapentin have been shown to be both effective and well tolerated; however, it is not clear which is preferred. PATIENTS AND METHODS: This was a group-sequential, open-label, randomized, cross-over trial of 4 weeks of venlafaxine (37.5 mg daily for 7 days followed by 75 mg daily for 21 days) versus gabapentin (300 mg once per day for 3 days, then 300 mg twice per day for 3 days, then 300 mg three times per day for 22 days), with patient preference as the primary outcome. Postmenopausal women with at least 14 bothersome hot flashes per week for the prior month were eligible. A 2-week baseline period and a 2-week tapering/washout time was used before the first and second treatment periods, respectively. Diaries were used to measure hot flashes and potential toxicities throughout the study. Participants completed a preference questionnaire at the end of the study. A predefined Pocock stopping rule was applied. Patient preference and hot flash and toxicity outcomes were compared between treatments. RESULTS: Sixty-six patients were randomly assigned, 56 of whom provided a preference (eight dropped out and two had no preference); 18 (32%) preferred gabapentin and 38 (68%) preferred venlafaxine (P = .01). Both agents reduced hot flash scores to a similar extent (66% reduction). Venlafaxine was associated with increased nausea, appetite loss, constipation, and reduced negative mood changes compared with gabapentin, whereas gabapentin was associated with increased dizziness and appetite compared with venlafaxine (all P < .05). CONCLUSION: Breast cancer survivors prefer venlafaxine over gabapentin for treating hot flashes.