The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations.

BACKGROUND: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. METHODS: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. RESULTS: During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. CONCLUSION: The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary.

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Importance: Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. Objective: To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. Design, Setting, and Participants: In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023. Exposures: Self-reported bilateral oophorectomy (with or without salpingectomy). Main Outcomes and Measures: All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. Results: There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy. Conclusions and Relevance: In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Importance: Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. Objective: To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Design, Setting, and Participants: Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Exposures: Entrance into an MRI surveillance program. Main Outcomes and Measures: Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. Results: A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Conclusion and Relevance: Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.

Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis.

BACKGROUND: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. METHODS: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. RESULTS: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05-1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. CONCLUSIONS: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.

Predicting Blood Pressure After Nitroglycerin Infusion Dose Titration in Critical Care Units: A Multicenter Retrospective Study.

Critical care nurses use physiological indicators, such as blood pressure, to guide their decision-making regarding the titration of nitroglycerin infusions. A retrospective study was conducted to determine the accuracy of systolic blood pressure predictions during nitroglycerin infusions. Data were extracted from the publicly accessible eICU program database. The accuracy of a linear model, least absolute shrinkage and selection operator, ridge regression, and a stacked ensemble model trained using the AutoGluon-Tabular framework were investigated. A persistence model, where the future value in a time series is predicted as equal to its preceding value, was used as the baseline comparison for model accuracy. Internal-external validation was used to examine if heterogeneity among hospitals could contribute to model performance. The sample consisted of 827 patients and 2541 nitroglycerin dose titrations with corresponding systolic blood pressure measurements. The root-mean-square error on the test set for the stacked ensemble model developed using the AutoGluon-Tabular framework was the lowest of all models at 15.3 mm Hg, equating to a 22% improvement against the baseline. Internal-external validation revealed consistent accuracy across hospitals. Further studies are needed to determine the impact of using systolic blood pressure predictions to inform nurses' clinical decision-making regarding nitroglycerin infusion titration in critical care.

Recontact to return new or updated PALB2 genetic results in the clinical laboratory setting.

OBJECTIVE: The purpose of this study was to recontact individuals with clinically actionable test results identified through a retrospective research study and to provide a framework for laboratories to recontact patients. METHODS: Genetic testing was conducted on 2977 individuals originally referred for BRCA1 and BRCA2 hereditary breast and ovarian cancer testing that had a negative genetic test result. A gene panel was used to identify pathogenic variants in known or newly discovered genes that could explain the underlying cause of disease; however, analysis was restricted to PALB2 for the purposes of this study. A patient recontact decision tree was developed to assist in the returning of updated genetic test results to clinics and patients. RESULTS: Novel clinically actionable pathogenic variants were identified in the PALB2 gene in 18 participants (0.6%), the majority of whom were recontacted with their new or updated genetic test results. Eight individuals were unable to be recontacted; five individuals had already learnt about their new or updated findings from genetic testing outside the context of this study; three individuals prompted cascade testing in family members; two individuals were deceased. CONCLUSION: Novel pathogenic variants in PALB2 were identified in 18 individuals through retrospective gene panel testing. Recontacting these individuals regarding these new or updated findings had a range of outcomes. The process of conveying genomic results within this framework can be effectively accomplished while upholding patient autonomy, potentially leading to advantageous outcomes for patients and their families.

Theory-based behavior change intervention to increase uptake of risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 pathogenic variant: The PREVENT randomized controlled trial.

OBJECTIVE: To evaluate the effect of a theory-based behavioral intervention delivered by genetic counselors on the uptake of risk-reducing salpingo-oophorectomy (RRSO) at 12 and 24 months by women with a BRCA1 or BRCA2 pathogenic variant (PV) compared to women who received usual care. METHODS: In this two-arm, multi-site randomized controlled trial participants were randomized to receive a theoretically-guided behavioral telephone intervention or usual care. Outcome data were collected at 12 and 24 months. Participants in the usual care arm were offered the intervention after 12 months. RESULTS: Data on 107 participants were included in the analysis. There was no significant difference in the proportion of women who had a RRSO by 1 year (28.6%- intervention; 22.9%- usual care (p = 0.54)). At 1 year, women who received the intervention had significantly lower mean decisional conflict (pinteraction <0.001) and a higher mean knowledge score at one-year compared to usual care (pinteraction <0.001). At 2 years, 53.9% of participants in the intervention arm had RRSO compared to 32.6% in usual care (p = 0.05). CONCLUSIONS: A theory-based behavioral intervention delivered by genetic counselors to women with a BRCA PV who chose not to have the recommended RRSO was effective at reducing decisional conflict and increasing knowledge in women with a BRCA1 or BRCA2 PV.

Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.

PURPOSE: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation. METHODS: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis. RESULTS: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07). CONCLUSION: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary.

Patient Outcomes after Fat Grafting to the Radiated Chest Wall before Delayed Two-stage Alloplastic Breast Reconstruction.

Two-stage alloplastic breast reconstruction in patients having received mastectomy and radiation is associated with a high rate of complications. Fat grafting has been shown to mitigate the effects of radiation on the chest wall to allow for alloplastic reconstruction. In this study, we assess the outcomes (after a mean follow-up of 28 months), including complications and revisional procedures, of women who had fat grafting to the radiated chest wall before two-stage implant-based breast reconstruction. Methods: A retrospective chart review was performed on consecutive patients seeking delayed implant-based reconstruction after simple mastectomy and postmastectomy radiation therapy between 2011 and 2015. All patients underwent two sessions of fat grafting to the radiated chest wall before inserting a tissue expander and subsequent exchange to a silicone implant. Results: Twenty patients were included in the study. No reconstructive failures were recorded. The short-term complication rate was 5%, with one hematoma leading to a revisional procedure. The mean follow-up after reconstruction was 28 months. During follow-up, two patients (10%) developed capsular contracture grade IV with implant malposition, leading to capsular revision and implant exchange. Four patients (20%) underwent additional fat grafting for contour deformities. Conclusions: Fat grafting before two-stage alloplastic breast reconstruction in patients treated with mastectomy and postmastectomy radiation therapy may provide an alternate method of alloplastic reconstruction in a select group of patients who are not suitable for autogenous reconstruction. Follow-up data show that additional surgery may be required for correction of implant malposition and capsular contracture.

Genetic testing women with newly diagnosed breast cancer: What criteria are the most predictive of a positive test?

BACKGROUND: Knowledge of pathogenic variants in cancer-predisposing genes is important when making breast cancer treatment decisions, but genetic testing is not universal and criteria must be met to qualify for genetic testing. The objective of this study was to evaluate the pathogenic variant yield for nine cancer predisposition genes by testing criteria, singly and in combination. METHODS: Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four centers in Toronto, Canada. Participants completed a demographics and family history questionnaire and clinical characteristics were collected from medical charts. Genetic testing was done for BRCA1, BRCA2, PALB2, ATM, CHEK2, BRIP1, RAD51D, RECQL, and TP53. Pathogenic variant frequencies were calculated according to five criteria (age ≤ 50, triple-negative breast cancer, family history, bilateral breast cancer, or Jewish ethnicity). RESULTS: Of the 1006 women studied, 100 women (9.9%) were found to have a pathogenic variant in one of the nine genes tested. The highest prevalence of pathogenic variants was found in women with triple-negative breast cancer (23%). Of the 100 pathogenic variants detected, 78 were detected in women diagnosed at age 50 or less. A total of 96% of the mutations were identified with three criteria (age of diagnosis, family history, and triple-negative status). CONCLUSIONS: Genetic testing criteria for women with breast cancer should include women with triple-negative breast cancer, regardless of age. All women aged 50 years or below at time of breast cancer diagnosis should be offered genetic testing.

The risks of cancer in older women with BRCA pathogenic variants: How far have we come?

BACKGROUND: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. METHODS: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow-up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow-up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan-Meier method. RESULTS: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk-reducing mastectomy and bilateral salpingo-oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. CONCLUSION: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately.

Patient-reported outcomes associated with reflex BRCA1/2 tumor and subsequent germline panel genetic testing for high-grade serous ovarian cancer.

Reflex genetic testing of tumor tissue is being completed to direct cancer treatment; however, the patient impact of this genetic testing model is unknown. This survey study evaluates psychological outcomes following tumor and germline genetic testing in individuals with a new diagnosis of high-grade serous ovarian cancer (HGSOC). Individuals were recruited from two hospitals in Toronto, Canada. Participants completed surveys 1 week after receiving tumor results and 1 week after receiving germline results (which included genetic counseling). Outcomes included cancer-related distress (Impact of Events Scale: IES), genetic testing-related distress (Multidimensional Impact of Cancer Risk Assessment: MICRA), and patient satisfaction. Paired t-tests were used to evaluate differences in outcomes following each genetic test result; Cohen's d was used to evaluate effect size. Subgroup analyses were undertaken according to age at diagnosis (<60 years vs. ≥60 years) and test results (any positive vs. both negative). McNemar's test assessed differences in satisfaction. Fifty-two individuals were included in the analyses. Mean IES scores were similar following disclosure of tumor and germline results (27.39 vs. 26.14; p = 0.481; d = 0.101). Compared to following tumor result disclosure, MICRA scores were significantly lower following receipt of germline results with genetic counseling (27.23 vs. 22.69; p = 0.007; d = 0.435). Decreases in MICRA scores from tumor to germline result disclosure were greater for those diagnosed <60 years or those who received only negative test results. Most individuals were satisfied/highly satisfied following tumor (85.7%) and germline (89.8%) results disclosure (p = 0.774). Reflex tumor, and subsequent germline, genetic testing is a new model of care for cancer patients. In our cohort, genetic testing-related distress decreased significantly following receipt of germline results with genetic counseling, especially for individuals diagnosed under 60 years and those receiving only negative results. Most individuals were satisfied with this model of care.

A Qualitative Study of the Everyday Impacts of Cognitive Difficulties After Stem Cell Transplantation.

PURPOSE: To explore how cognitive difficulties affect the everyday lives of survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT). PARTICIPANTS & SETTING: 20 survivors of allo-HSCT attending follow-up care at a tertiary cancer center in Toronto, Canada. METHODOLOGIC APPROACH: This qualitative, descriptive study used semistructured interviews. FINDINGS: Cognitive symptoms affected the everyday lives of allo-HSCT survivors by changing the experience of everyday tasks, provoking emotional responses, and prompting adoption of mitigation strategies. Subthemes within each of these themes highlight the ways in which cognitive impairment shapes how allo-HSCT survivors feel about themselves, interact with others, and navigate coping challenges. IMPLICATIONS FOR NURSING: These findings demonstrate the multidimensional experience of cognitive difficulties following allo-HSCT and may inform the development of patient-centered approaches to assessing and managing cognitive difficulties.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention.

Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit "Gynecologic Cancer Prevention: Thinking Big, Thinking Differently" in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.

Psychological and health behaviour outcomes following multi-gene panel testing for hereditary breast and ovarian cancer risk: a mini-review of the literature.

INTRODUCTION: Knowledge of the genetic mechanisms driving hereditary breast and ovarian cancer (HBOC) has recently expanded due to advances in gene sequencing technologies. Genetic testing for HBOC risk now involves multi-gene panel testing, which includes well characterized high-penetrance genes (e.g. BRCA1 and BRCA2), as well as moderate- and low-penetrance genes. Certain moderate and low penetrance genes are associated with limited data to inform cancer risk estimates and clinical management recommendations, which create new sources of genetic and clinical uncertainty for patients. PURPOSE: The aim of this review is to evaluate the psychological and health behaviour outcomes associated with multi-gene panel testing for HBOC risk. The search was developed in collaboration with an Information Specialist (Princess Margaret Cancer Centre) and conducted in the following databases: MEDLINE, EMBASE, EMCare, PsycINFO, Epub Ahead of Publication. RESULTS: Similar to the BRCA1/2 literature, individuals with a pathogenic variant (PV) reported higher levels of testing-related concerns and cancer-specific distress, as well as higher uptake of prophylactic surgery in both affected and unaffected individuals compared to those with variant of uncertain significance (VUS) or negative result. A single study demonstrated that individuals with a PV in a moderate penetrance gene reported higher rates of cancer worry, genetic testing concerns and cancer-related distress when compared to women with high penetrance PV. Analysis of cancer screening and prevention outcomes based upon gene penetrance were limited to two studies, with conflicting findings. CONCLUSION: The findings in this review emphasize the need for studies examining psychological and health behavior outcomes associated with panel testing to include between group differences based upon both variant pathogenicity and gene penetrance. Future studies evaluating the impact of gene penetrance on patient-reported and clinical outcomes will require large samples to be powered for these analyses given that a limited number of tested individuals are found to have a PV.

The development of a patient decision aid to reduce decisional conflict about antidepressant use in pregnancy.

BACKGROUND: People with moderate to severe depression in pregnancy must weigh potential risks of untreated or incompletely treated depression against the small, but uncertain risks of fetal antidepressant drug exposure. Clinical support alone appears insufficient for helping individuals with this complex decision. A patient decision aid (PDA) has the potential to be a useful tool for this population. The objective of our work was to use internationally recognized guidelines from the International Patient Decision Aids Standards Collaboration to develop an evidence-based PDA for antidepressant use in pregnancy. METHODS: A three-phased development process was used whereby, informed by patient and physician perspectives and evidence synthesis, a steering committee commissioned a web-based PDA for those deciding whether or not to start or continue antidepressant treatment for depression in pregnancy (Phase 1). A prototype was developed (Phase 2) and iteratively revised based on feedback during field testing based on a user-centred process (Phase 3). RESULTS: We developed a web-based PDA for people deciding whether to start or continue antidepressant use for depression in pregnancy. It has five interactive sections: (1) information on depression and treatment; (2) reasons to start/continue an antidepressant and to start/stop antidepressant medication; (3) user assessment of values regarding each issue; (4) opportunity to reflect on factors that contribute to decision making; and (5) a printable PDF that summarizes the user's journey through the PDA. CONCLUSIONS: This tool, which exclusively focuses on depression treatment with Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors, can be used by individuals making decisions about antidepressant use to treat depression during pregnancy. Limitations of the PDA are that it is not for other conditions, nor other medications that can be used for depression, and in its pilot form cannot be used by women who do not speak English or who have a visual impairment. Pending further study, it has the potential to enhance quality of care and patient experience.

Risk factors for psychological morbidity and the protective role of coping self-efficacy in young women with breast cancer early in diagnosis: a national multicentre cohort study.

PURPOSE: Young women with breast cancer (YWBC) are an understudied population and there are limited data on risk factors for psychological morbidity early in diagnosis. We examined psychological morbidity (anxiety, depression, stress symptoms), well-being and associated risk factors. METHODS: A total of 845 women from a pan-Canadian, multicentre inception cohort study of YWBC (age ≤ 40) who completed Patient Reported Outcome Measures (PROMs) after their initial surgical consultation and prior to surgical or other treatments were included. Multivariate regression analyses identified risk factors (i.e. parenting young children) associated with psychological morbidity and whether coping self-efficacy was protective. RESULTS: Rates of clinically significant anxiety (n = 683, 69.1%) and depression (n = 422, 42.7%) were high but lower for stress symptoms (n = 67, 6.8%). Probability of anxiety was high for women with a previous history of depression (OR 2.02, P = 0.03, CI 1.09-3.74) and working full-time (OR 1.76, P = 0.05 CI 1.02-2.77). Whereas, pre-existing depression (OR 2.91, P = 0.01, CI 1.36-6.01), younger children (age ≤ 10) (OR 1.69, P = 0.05, CI 1.01-2.93), and income > $100,000 (OR 2.06, P = 0.02, CI 1.18-3.64) were risk factors for depression. Coping self-efficacy was protective with a decreased risk of anxiety (OR 0.11, P ≤ 0.01 CI 0.04-0.28), depression (OR 0.03, P ≤ .01, CI 0.01-0.16), stress symptoms (OR 0.17, P ≤ .01, CI 0.04-0.65) and higher psychosocial well-being with a gain of 19.68 points (P < 0.01) for high levels of CSE (> mean plus 1 SD). Those with lower levels of neurosis had less negative outcomes. CONCLUSION: Young women with breast cancer are vulnerable to psychological morbidity early in diagnosis, particularly those with low coping self-efficacy and may benefit from earlier supportive care.

Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal.

BACKGROUND: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case-control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. METHODS: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. RESULTS: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34-0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87-1.70; P = 0.26). CONCLUSIONS: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. IMPACT: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Reflex BRCA1 and BRCA2 tumour genetic testing for high-grade serous ovarian cancer: streamlined for clinicians but what do patients think?

BACKGROUND: Reflex (automatic) BRCA1 and BRCA2 (BRCA1/2) genetic testing of tumour tissue is being completed for all newly diagnosed high-grade serous ovarian cancer (HGSOC) in the province of Ontario, Canada. The objective of this study was to measure the psychological impact of tumour genetic testing among individuals with a new diagnosis of HGSOC. METHODS: Participants had a new diagnosis of HGSOC and received reflex BRCA1/2 tumour genetic testing as a component of their care. Eligible individuals were recruited from two oncology centres in Toronto, Canada. One week after disclosure of tumour genetic test results, consenting participants were asked to complete a questionnaire that measured cancer-related distress, dispositional optimism, knowledge of hereditary breast/ovarian cancer, recall of tumour genetic test results, satisfaction, and the psychological impact of receiving tumour genetic test results. The Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire was used to measure the psychological impact of tumour genetic testing. RESULTS: 76 individuals completed the study survey; 13 said they did not receive their tumour test results. Of the remaining 63 participants, the average MICRA score was 26.8 (SD = 16.3). Higher total MICRA scores were seen among those with children (p = 0.02), who received treatment with primary surgery (p = 0.02), and had higher reported cancer-related distress (p < 0.001). Higher dispositional optimism (p < 0.001) and increasing age (p = 0.03) were associated with lower total MICRA scores. Most (83.5%) participants reported being satisfied/highly satisfied with having tumour testing completed; however, 40.8% could not accurately recall their tumor test results. CONCLUSIONS: This study is the first to assess psychological outcomes following reflex BRCA1/2 tumour genetic testing in women newly diagnosed with HGSOC. Increased dispositional optimism provided a protective effect, while increased cancer-related distress increased the psychological impact of tumour genetic testing. Educational resources are needed to help increase patient understanding and recall of tumour results, particularly when tumour genetic testing includes analysis of genes that may have implications for hereditary cancer risk. Additional research is required to better understand the patient experience of reflex tumour genetic testing.