Early change in fatigue, insomnia, and cognitive impairment and symptom severity 3 years post-treatment in breast cancer survivors.

PURPOSE: Breast cancer is the most common form of cancer among Canadian women. Survivorship challenges include fatigue, sleep disturbance, and cognitive impairment. This study examined (1) symptom trajectory from diagnosis to 3 years; (2) whether symptom change in the first 4 months was associated with prolonged difficulties after 3 years; and (3) which factors were associated with deterioration in symptoms during the first 4 months. METHODS: This prospective observational cohort study examined 53 women (Mage = 58.6, 96.2% White, 67.9% stage I) with newly diagnosed breast cancer over 3 years. Women completed assessments before starting treatment, 4 months, and 3 years after diagnosis. Three-way repeated-measures ANOVAs evaluated symptom trajectories. A repeated-measures mediation analysis was performed to determine if change from pre-treatment to 4 months accounted for change from pre-treatment to 3 years. A series of between-subjects ANOVAs were used to determine what variables significantly differed by deterioration status. RESULTS: Perceived cognitive impairment and fatigue increased linearly from diagnosis to 3 years. Change in fatigue in the first 4 months fully accounted for its change over 3 years. Insomnia severity and sleep quality deteriorated from diagnosis to 4 months, but returned to pre-treatment levels at 3 years. Those whose fatigue and cognitive ability deteriorated during the first 4 months were younger. CONCLUSION: Efforts to identify those who are at risk of experiencing fatigue, sleep disturbance, and cognitive impairment; monitor patients early after receiving a diagnosis; and provide targeted interventions may prevent long-term deterioration and improve well-being.

Perceived Executive Functioning Deficits After Diagnosis in Women with Non-Metastatic Breast Cancer Prior to Adjuvant Therapies.

BACKGROUND: Perceived deficits in executive functioning are among the many difficulties that women diagnosed with breast cancer experience. This study assessed the presence of perceived deficits in executive functioning among women with breast cancer prior to systemic treatment and radiation and associations between perceived deficits in executive function and comorbid fatigue, sleep, and mood disturbance. METHOD: Participants were recruited following their breast cancer diagnosis and assessed using the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), subjective and objective measures of sleep duration and efficiency, and self-report measures of insomnia severity, sleep quality, fatigue, and mood disturbance. Hierarchical regression was used to examine associations between symptoms, adjusting for age and education. RESULTS: The final sample included 92 women with a mean age of 60.7 years and 13.5 years of education. Thirteen percent of participants reported global executive dysfunction. After partitioning out variability from other independent variables, fatigue (p = < .001), perceived sleep quality (p = .030), and symptoms of insomnia (p = .008) accounted for 13.3%, 5.7%, and 8.5% of unique variance in perceived executive functioning, respectively. Emotional fatigue was most strongly associated with perceived deficits in executive functioning. Neither subjective or objective sleep duration or efficiency was associated with perceived deficits in executive functioning. CONCLUSION: Fatigue, particularly emotional fatigue, insomnia, and poor sleep quality had the strongest associations with perceived deficits in executive functioning. Sleep interventions and fatigue management strategies may prove useful for women who seek to improve their perceived executive functioning.

Primary neuroendocrine tumor of the pineal gland: a case report.

INTRODUCTION: Primary intracranial neuroendocrine tumors are exceedingly rare, with few cases in the literature. We present a case of a primary neuroendocrine carcinoma of the pineal gland, which is the second that has ever been reported. CASE PRESENTATION: A 53-year-old male patient presented with vomiting, weakness, and headaches. Imaging revealed a lesion in the pineal region, which was surgically resected. This mass was characterized by histology as a neuroendocrine carcinoma, given the presence of neuroendocrine markers and cytokeratin markers with absence of a primary lesion elsewhere on imaging. CONCLUSIONS: There are currently no guidelines on the management of primary intracranial neuroendocrine tumors. In this case, the patient underwent surgical resection and craniospinal radiotherapy. He subsequently received one cycle of chemotherapy with temozolomide, an alkylating agent, but he unfortunately did not tolerate treatment. A multidisciplinary decision was made along with the patient and his family to focus on palliative care. Eighteen months after the initial presentation, disease recurred in the patient's neck. The patient underwent resection to control the metastases, with a plan to follow with radiotherapy and chemotherapy. Unfortunately, the patient became unwell and died at 21 months after initial diagnosis. This demonstrates a need for continued research and reporting on this uncommon disease entity.

Randomized Controlled Trial of Virtually Delivered Cognitive Behavioral Therapy for Insomnia to Address Perceived Cancer-Related Cognitive Impairment in Cancer Survivors.

PURPOSE: Comorbid insomnia and cancer-related cognitive impairment (CRCI) are experienced by up to 26% of individuals diagnosed with cancer. This study examined the efficacy and durability of cognitive behavioral therapy for insomnia (CBT-I) on perceived CRCI in cancer survivors. METHODS: Atlantic Canadian cancer survivors with insomnia and CRCI were randomly assigned to receive seven weekly virtual CBT-I sessions (n = 63) or placed in a waitlist control group (n = 69) to receive treatment after the waiting period. Participants completed assessments at baseline, 1 month (mid-treatment), and 2 months (post-treatment). Age- and education-adjusted mixed-effects models using intention-to-treat principles assessed change at post-treatment. Data from both groups were then pooled to assess the durability of effects at 3 and 6 months. A mediation analysis examined whether change in insomnia symptoms mediated the effect of CBT-I on cognitive outcomes. RESULTS: The mean age of the sample was 60 years, 77% were women, and breast cancer was the most common diagnosis (41%). The treatment group reported an 11.35-point reduction in insomnia severity, compared with a 2.67-point reduction in the waitlist control group (P < .001). The treatment group had a greater overall improvement than the waitlist control on perceived cognitive impairment (P < .001; d = 0.75), cognitive abilities (P < .001; d = 0.92), and impact on quality of life (P < .001; d = 1.01). These improvements were maintained at follow-up. Change in insomnia symptoms fully mediated the effect of CBT-I on subjective cognitive outcomes. CONCLUSION: Treating insomnia with CBT-I produces clinically meaningful and durable improvements in CRCI. There is an urgent need increase access to evidence-based treatment for insomnia in cancer centers and the community.

Use of bisphosphonates in metastatic breast cancer: single institution review at the Dr. H. Bliss Murphy Cancer Centre.

PURPOSE: Bone metastases occur in 65-75% of patients with metastatic breast cancer. These patients are at risk of developing skeletal-related events (SREs). SREs are defined as any pathological fracture, spinal cord compression, hypercalcemia, and surgery or radiation required for treatment of bone metastases. Bisphosphonates are used to prevent the development of SREs. The purpose of this study is to review the incidence of SREs in metastatic breast cancer patients with bony disease in Newfoundland and Labrador and to determine if there is an association between SREs and the type of bisphosphonate therapy given. METHODS: This retrospective chart review includes all metastatic breast cancer patients with bony disease treated at the Dr. H. Bliss Murphy Cancer Centre from 2008 to 2010. Patient demographics, treatment received, and treatment changes were collected. Patients at the Centre received bisphosphonate, pamidronate or zolendronic acid to prevent SREs. The prescribing pattern of bisphosphonates was collected. The occurrences of SREs were then compared to the type of treatment received. RESULTS: Sixty-five patients with breast cancer and bony metastasis were identified using the provincial tumor registry, three patients were excluded from the review as their charts could not be located. Following the initial diagnosis of bone metastasis, 8 patients (12.7%) were started on zolendronic acid, 50 patients (80.6%) were started on pamidronate, and 4 (6.4%) received no treatment. Six patients (75%) on zolendronic acid experienced one SRE; however, none experienced multiple SREs. Thirty-one patients (62%) on pamidronate experienced one SRE, and ten (20%) had multiple SREs. Of the 31 patients on pamidronate with an SRE, 4 (12.9%) were switched to zolendronic acid. Three of the four (75%) had multiple SREs despite treatment changes. Of the six patients on zolendronic acid with SREs, none were switched to pamidronate. CONCLUSION: Our results show that the majority of patients with breast cancer, who develop bony metastases in Newfoundland and Labrador, are initially treated with the bisphosphonate, pamidronate. Over 60% of these patients experienced at least one SRE, and 20% had more than two SREs. A small proportion of the patients were initially started on zolendronic acid, and this group had better outcomes with fewer SREs and none had more than two SREs. It appears that zolendronic acid is superior to pamidronate in preventing SREs; however, zolendronic acid is being used primarily as second-line in Newfoundland and Labrador.

A Population Description of Young Women with Breast Cancer in Newfoundland and Labrador.

It has been well established in the literature that young women tend to carry more aggressive subtypes of breast cancer than their older-aged counterparts. The objective of this study was to describe the characteristics and outcomes of young women with breast cancer. In this retrospective analysis, data were collected for women under the age of 40 years who were diagnosed with breast cancer between 2008 and 2018 in the province of Newfoundland and Labrador. Specifically, data were collected on demographics, staging, pathological characteristics, treatment, and survival outcomes for young women with this disease. Results demonstrate that most of these women were diagnosed between the age of 35 and 39 years (91.2%). Most women presented with early-stage disease (stage I and II-66.4%), while 24% were stage III and 9.6% presented with stage IV metastatic disease. The prevalence of hormone-receptor-positive disease represented 41.9% of the cohort, with triple-negative and HER2+ measuring 27.7% and 30.4%, respectively. Five-year disease-free survival was 80.5% and overall survival was 82.7%. These findings provoke discussion regarding the intersecting roles of genetics, environment, and lifestyle in a region with some of the highest rates of malignancy in the country.

Specialty Care and Counselling about Hereditary Cancer Risk Improves Adherence to Cancer Screening and Prevention in Newfoundland and Labrador Patients with BRCA1/2 Pathogenic Variants: A Population-Based Retrospective Cohort Study.

Pathogenic variants (PVs) in BRCA1 and BRCA2 increase the lifetime risks of breast and ovarian cancer. Guidelines recommend breast screening (magnetic resonance imaging (MRI) and mammogram) or risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO). We sought to (1) characterize the population of BRCA1/2 PV carriers in Newfoundland and Labrador (NL), (2) evaluate risk-reducing interventions, and (3) identify factors influencing screening and prevention adherence. We conducted a retrospective study from a population-based provincial cohort of BRCA1/2 PV carriers. The eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommendations. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. A total of 276 BRCA1/2 PV carriers were identified; 156 living NL biological females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 years versus 51.7 years; p = 0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0%, and 75.7% of patients underwent MRI, mammogram, RRM, and RRSO, respectively. Individuals with breast cancer were more likely to have RRM (64.7% versus 35.3%; p < 0.001), and those who attended a specialty hereditary cancer clinic were more likely to be adherent to recommendations (73.2% versus 13.4%; p < 0.001) and to undergo RRSO (84.1% versus 15.9%; p < 0.001). Nearly 40% of the female BRCA1/2 PV carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian healthcare systems and have the potential to reduce the burden of disease countrywide.

Molecular alterations between the primary breast cancer and the subsequent locoregional/metastatic tumor.

BACKGROUND: Metastatic breast cancers have historically been presumed to have the same predictive biomarkers as the initial primary tumor. We compared the expression of these biomarkers in a large paired tissue microarray (TMA) series of primary and subsequent relapsed tumors. METHODS: Using the British Columbia Cancer Agency Breast Cancer Outcomes Unit database, patients with biopsy-proven relapses were identified and linked to a large TMA series of primary breast cancers from 1986-1992. Charts were reviewed, and tissue blocks of the metastatic cancer were collected to create a separate TMA. Immunohistochemical assessment with the same antibodies and conditions was performed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2 on both the primary and relapsed tumors. RESULTS: One hundred sixty cases were received that had tumor adequate for analyses. Of these, 71.9% had no changes in either the ER or PR status or HER-2 status. Of the 45 (28.1%; 95% confidence interval [CI], 21.2%-35.1%) tumors that did have changes in receptor status, 7.5% were in-breast recurrences or new breast primaries, 4.4% had changes in PR status only and were therefore deemed clinically irrelevant, and 19.4% (95% CI, 13.3%-25.5%) had changes in either the ER or HER-2 status from regional or distant relapses. Five percent of tumors had a receptor status change going from ER(+) or PR(+) to ER(-) or PR(-); 9.4% went from ER(-) or PR(-) to ER(+) or PR(+). With regard to HER-2 status, 3.8% of tumors went from positive to negative and 1.3% went from negative to positive. For all discordant cases, biopsies of the relapsed lesion were obtained prior to initiation of first-line treatment for metastatic disease. In the primary tumors that were ER(+), time to relapse was significantly shorter in the discordant relapsed cases than in the concordant ones (p = .0002). Changes in loss or gain of either biomarker were seen across the discordant cases. CONCLUSIONS: A significant proportion of relapsed tumors had changes in either ER or HER-2 status, which would dramatically alter treatment recommendations and clinical behavior. This study suggests that biopsies of relapsed and metastatic breast cancers should be performed routinely in clinical practice.

Cancer prevention in cancer predisposition syndromes: A protocol for testing the feasibility of building a hereditary cancer research registry and nurse navigator follow up model.

Monogenic, high penetrance syndromes, conferring an increased risk of malignancies in multiple organs, are important contributors to the hereditary burden of cancer. Early detection and risk reduction strategies in patients with a cancer predisposition syndrome can save their lives. However, despite evidence supporting the benefits of early detection and risk reduction strategies, most Canadian jurisdictions have not implemented programmatic follow up of these patients. In our study site in the province of Newfoundland and Labrador (NL), Canada, there is no centralized, provincial registry of high-risk individuals. There is no continuity or coordination of care providing cancer genetics expertise and no process to ensure that patients are referred to the appropriate specialists or risk management interventions. This paper describes a study protocol to test the feasibility of obtaining and analyzing patient risk management data, specifically patients affected by hereditary breast ovarian cancer syndrome (HBOC; BRCA 1 and BRCA 2 genes) and Lynch syndrome (LS; MLH1, MSH2, MSH6, and PMS2 genes). Through a retrospective cohort study, we will describe these patients' adherence to risk management guidelines and test its relationship to health outcomes, including cancer incidence and stage. Through a qualitative interviews, we will determine the priorities and preferences of patients with any inherited cancer mutation for a follow up navigation model of risk management. Study data will inform a subsequent funding application focused on creating and evaluating a research registry and follow up nurse navigation model. It is not currently known what proportion of cancer mutation carriers are receiving care according to guidelines. Data collected in this study will provide clinical uptake and health outcome information so gaps in care can be identified. Data will also provide patient preference information to inform ongoing and planned research with cancer mutation carriers.

Rationale and protocol for a randomized waitlist controlled trial of videoconference delivered cognitive behaviour therapy for insomnia (CBT-I) to improve perceived cognitive impairment (PCI) among cancer survivors.

Perceived cognitive impairment (PCI) and sleep disturbances (such as insomnia) are commonly reported barriers preventing cancer survivors from resuming normal functioning. Cognitive-behaviour therapy for insomnia (CBT-I) is the treatment of choice for insomnia among cancer survivors. Literature suggests that treatment with CBT-I may lead to an improvement in PCI, but this needs to be tested in a sample of patients with PCI at study entry with cognitive impairments as the primary study outcome. Here we describe the design of a clinical trial to evaluate the efficacy of videoconference-delivered CBT-I for the improvement of PCI among cancer survivors. This project is a randomized waitlist-controlled trial with a recruitment target of 124 adult cancer survivors (solid tumors and hematological malignancies) who have completed primary treatment at least 6 months prior, report PCI and meet criteria for insomnia disorder. Participants will complete assessments at baseline, 4 weeks (mid-treatment), 8 weeks (post treatment), and 3 and 6 months post-treatment. The primary outcome is the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog). Treatment of PCI in cancer patients is a priority for clinicians, researchers, and patients. This research will increase our understanding of the mechanisms of cognitive impairment associated with cancer, and potentially expand currently available treatment options.

Medical Assistance in Dying: the opinions of medical trainees in Newfoundland and Labrador. A cross- sectional study.

BACKGROUND: Medical Assistance in Dying (MAiD) was legalized in Canada in 2016. As future physicians, medical trainees may face decisions regarding MAiD. Although many publications exist internationally, Canadian data is limited in the peer-reviewed literature, particularly following legalization. The purpose of this study is to determine the opinions of medical trainees in Newfoundland and Labrador regarding MAiD, and the factors that impact these views. METHODS: A survey was distributed to all under- and postgraduate medical trainees at Memorial University (N=570), the only medical school in Newfoundland and Labrador. The survey collected demographic information and opinions regarding MAiD. Respondents were divided into groups based on demographic characteristics, and their responses analyzed using non-parametric statistics. RESULTS: The survey was completed by 124 trainees. Ninety percent of respondents agreed with the legalization of MAiD in Canada and nearly 60% stated they would perform the procedure for their patients. Several factors influenced the opinions of medical trainees, including level of training and religious affiliation. Trainees also favored detachment from the MAiD process. INTERPRETATION: Medical trainees in Newfoundland and Labrador are largely in favor of MAiD. This may highlight the importance of emphasizing MAiD within medical curricula, so that trainees are adequately informed and prepared for this new aspect of medical care upon joining independent practice.

CONTEXTE: L'aide médicale à mourir a été légalisée au Canada en 2016. En tant que futurs médecins, les apprenants en médecine devront peut-être prendre des décisions concernant l'aide médicale à mourir. Bien qu'il existe plusieurs publications au niveau international, les données canadiennes sous forme d'articles évalués par des pairs sont limitées. Cette étude vise à connaître les opinions des apprenants en médecine de Terre-Neuve-et-Labrador concernant l'aide médicale à mourir, et déterminer les facteurs qui influencent leurs points de vue. MÉTHODES: Un sondage a été distribué à tous les étudiants en médecine et résidents de l'Université Memorial (N=570), la seule faculté de médecine à Terre-Neuve-et-Labrador. Ce sondage a recueilli des informations démographiques et des opinions concernant l'aide médicale à mourir. Les personnes interrogées ont été divisées en groupes établis selon des caractéristiques démographiques, et leurs réponses ont été analysées à l'aide de statistiques non paramétriques. RÉSULTATS: 124 apprenants ont complété le sondage. 90 pour cent des personnes interrogées étaient en faveur de la légalisation de l'aide médicale à mourir au Canada et près de 60 % ont indiqué leur intention d'effectuer cette intervention auprès de leurs patients. Plusieurs facteurs ont influencé les opinions des stagiaires en médecine, notamment le niveau de formation et l'affiliation religieuse. Les stagiaires ont également favorisé le détachement face au processus d'aide médicale à mourir. INTERPRÉTATION: Les apprenants en médecine de Terre-Neuve-et-Labrador sont très favorables à l'aide médicale à mourir. Ces résultats font ressortir l'importance d'intégrer l'aide médicale à mourir aux programmes d'études en médecine pour bien informer et préparer les stagiaires à cette nouvelle dimension des soins médicaux avant de débuter leur pratique.

What is the difference between triple-negative and basal breast cancers?

Triple-negative breast cancer (TNBC) represents a phenotype defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression. Because TNBCs have more aggressive features and lack a therapeutic target, they have become a key topic of clinical and research interest within the oncology community. With advancements in the field of molecular biology, gene expression profiling has resulted in the identification of intrinsic subtypes including basal-like breast cancers (BLBCs). Although often thought to be synonymous, TNBC and BLBC represent different biologic phenomena. Furthermore, even within the basal-like subtype, diversity exists. The purpose of this review is to outline the most current evidence in an attempt to answer the question: what is BLBC?

Encapsulated apocrine papillary carcinoma of the breast--a tumour of uncertain malignant potential: report of five cases.

Five cases of an unusual encapsulated apocrine papillary tumour are reported. All presented as cystic masses in the breast of women aged 44-84 years. Imaging studies showed a complex cyst often with one or more mural nodules. The key histological features are similar to those of classical encapsulated papillary carcinoma in that myoepithelial cells were absent within the papillary structures and at the periphery of the cyst. All were pure apocrine in type and showed variable degrees of cytological atypia and mitotic activity. All lacked evidence of malignancy in the breast tissue outside of the lesion. Sentinel lymph node biopsies performed in three of the cases were negative for metastases, and all have behaved in a benign fashion.