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Background: Our understanding of how testing for and mutations of the BRCA1 and BRCA2 genes affect cancer risk and the use of risk-reduction strategies comes largely from studies of women recruited from specialized genetics clinics. Our aim was to assemble a generalizable cohort of women who underwent BRCA1/BRCA2 testing (the What Comes Next Cohort), irrespective of test result, to enable study of health care utilization and outcomes after testing. Methods: This descriptive study included adult women (≥ 18 yr) who met at least 1 of 13 provincial criteria for BRCA1/BRCA2 testing and who underwent genetic testing at sites in Ontario, Canada, from 2007 to 2016. Most of the women were tested at 1 of 2 main sites, which together capture about 70% of all BRCA1/BRCA2 testing in the province. We collected detailed demographic, genetic testing and family history data through chart review for linkage with data from administrative health databases providing information on cancer history before and after testing. We followed all women to September 2019, evaluating the demographic characteristics of the cohort, indications for testing and test results. Results: We identified 15 986 women (mean age 52.5 [standard deviation 13.9] yr) who underwent BRCA1/BRCA2 testing. Of these, 2033 women had positive results, 1175 women had variants of uncertain significance, and 12 778 women had negative results. Positive yields were 41.0% (955/2329) for predictive testing (for familial variants), 10.4% (216/2072) for Ashkenazi Jewish founder testing and 7.4% (862/11 585) for complete gene analysis. Six of the 13 provincial testing criteria had less than 10% positive yield. Among 403 women who tested negative for Ashkenazi Jewish founder mutations and subsequently underwent complete gene analysis, 12 (3.0%) tested positive for alternate pathogenic or likely pathogenic variants in the BRCA1 or BRCA2 gene. Interpretation: Several provincial eligibility criteria for BRCA1/BRCA2 testing led to positive results in less than 10% of cases. How testing influences women’s health care behaviours, particularly those with negative results and those found to carry variants of uncertain significance, is unknown; the What Comes Next Cohort will be instrumental in the study of long-term implications of BRCA1/BRCA2 testing.

Rates of bilateral mastectomy are rising in women with unilateral, nonhereditary breast cancer. We aim to characterize how psychosocial outcomes evolve after breast cancer surgery. We performed a prospective cohort study of women with unilateral, sporadic stage 0–III breast cancer at University Health Network in Toronto, Canada between 2014 and 2017. Women completed validated psychosocial questionnaires (BREAST-Q, Impact of Event Scale, Hospital Anxiety & Depression Scale) preoperatively, and at 6 and 12 months following surgery. Change in psychosocial scores was assessed between surgical groups using linear mixed models, controlling for age, stage, and adjuvant treatments. P < .05 were significant. A total of 475 women underwent unilateral lumpectomy (42.5%), unilateral mastectomy (38.3%), and bilateral mastectomy (19.2%). There was a significant interaction (P < .0001) between procedure and time for breast satisfaction, psychosocial and physical well-being. Women having unilateral lumpectomy had higher breast satisfaction and psychosocial well-being scores at 6 and 12 months after surgery compared with either unilateral or bilateral mastectomy, with no difference between the latter two groups. Physical well-being declined in all groups over time; scores were not better in women having bilateral mastectomy. While sexual well-being scores remained stable in the unilateral lumpectomy group, scores declined similarly in both unilateral and bilateral mastectomy groups over time. Cancer-related distress, anxiety, and depression scores declined significantly after surgery, regardless of surgical procedure (P < .001). Psychosocial outcomes are not improved with contralateral prophylactic mastectomy in women with unilateral breast cancer. Our data may inform women considering contralateral prophylactic mastectomy.

Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death. We studied 596 women with Stage I to III breast cancer. For each woman we estimated the five-year risk of death based on SEER data from 2010 to 2019. For each woman we measured anxiety and cancer-related distress levels shortly after surgery and one year later. The mean estimated five-year survival was 95%. At one week post-surgery, 59% of women had a clinically significant level of anxiety and 74% had a clinically significant level of cancer-related distress. There was no correlation between the objective risk of death and the level of anxiety or distress, at one week or at one year. Many women diagnosed with early-stage breast cancers experience significant levels of anxiety and distress. The emotional response to a breast cancer diagnosis is not related to the risk of death per se and other factors should be explored.

Survivors of allogeneic hematopoietic stem cell transplantation (alloHCT) may experience cognitive impairment over time post-treatment, but early identification of these individuals is limited. We previously reported a prospective evaluation of cognitive functioning over the first 6 months of alloHCT. Here, we report an extension of this study, with specific aims to (1) evaluate the trajectory of cognitive outcomes over the first 6 years post-alloHCT, and (2) determine the extent to which late cognitive impairment is predicted by earlier impairment. Participants completed objective and subjective cognitive measures before alloHCT, and at 100 days, 6 months, and 6 years post-alloHCT. Outcome trajectories were determined using linear mixed effects models. Relationships between early and late cognitive impairment were assessed using logistic regression and receiver operator curves. This analysis is based on longitudinal data from 59 participants, of whom 20 provided data at 6-year follow-up. Longitudinal models revealed an overall stability of cognitive outcomes over time, except for psychomotor efficiency/processing speed performance, which significantly improved (p = .049). However, poor learning/memory and cognitive complaints were persistently observed. At 6 years, 40% of relapse-free survivors met the impairment criteria. Impairment at 100 days was associated with impairment 6 years (OR = 20.00, p = .028) and demonstrated good accuracy in classifying those who were impaired and not impaired at 6 years (AUC = .79; 95% CI = .56-1.00). Poor cognitive outcomes among long-term alloHCT survivors are associated with cognitive functioning during the early post-treatment period. Early identification of survivors likely to experience poor cognitive outcomes may be possible, enabling timely intervention to mitigate long-term negative impacts.

Objective This study compares the rate and time to genetic referral, and patient uptake of germline genetic services, before and after implementation of reflex BRCA1/2 tumor testing for high-grade serous ovarian cancer (HGSOC) in a universal healthcare system. Methods A retrospective chart review of HSGOC patients diagnosed in the year before (PRE) and after (POST) implementation of reflex BRCA1/2 tumor testing was conducted. Clinical information (date/age at diagnosis, personal/family history of breast/ovarian cancer, cancer stage, primary treatment, tumor results) and dates of genetics referral, counseling, and germline testing were obtained. Incident rate ratios (IRR) and 95% CI were calculated using negative binomial regression. Time to referral was evaluated using Kaplan-Meier survival analysis. Fisher Exact tests were used to evaluate uptake of genetic services. Results 175 HGSOC patients were identified (81 PRE; 94 POST). Post-implementation of tumor testing, there was a higher rate of genetics referral (12.88 versus 7.10/1000 person-days; IRR = 1.60, 95% CI: 1.07–2.42) and a shorter median time from diagnosis to referral (59 days PRE, 33 days POST; p = .04). In the POST cohort, most patients were referred prior to receiving their tumor results (n = 63/77; 81.8%). Once referred, most patients attended genetic counseling (94.5% PRE, 97.6% POST; p = .418) and pursue germline testing (98.6% PRE; 100% POST; p = .455). Conclusions Following implementation of reflex BRCA1/2 tumor testing for HGSOC, significant improvements to the rate and time to genetics referral were identified. Additional studies are needed to evaluate physician referral practices and the long-term impact of reflex tumor testing.

Background Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancers. We sought to estimate the prevalence of cancer-related distress and to identify predictors of distress in an international sample of unaffected women with a BRCA mutation. Methods Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the United States, Canada, the United Kingdom, Australia and from a national advocacy group. Using an online survey, we asked about cancer risk reduction options and screening, and we measured cancer-related distress using the Impact of Event Scale. Results Among 576 respondents, mean age was 40.8 years (SD = 8.1). On average 4.9 years after a positive test result, 16.3% of women reported moderate-to-severe cancer-related distress. Women who had undergone risk-reducing breast and ovarian surgery were less likely to have (moderate or severe) cancer-related distress compared to other women (22.0% versus 11.4%, P value = 0.007). Women recruited from the advocacy group were more likely to have cancer-related distress than other women (21.6% versus 5.3%, P value = 0.002). Conclusions Approximately 16% of women with a BRCA1 or BRCA2 mutation experience distress levels comparable to those of women after a cancer diagnosis. Distress was lower for women who had risk-reducing surgery.

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

Background Decisions about antidepressant use in pregnancy are complex. Little is known about how pregnancy-planning and already pregnant women making these decisions differ. Methods In 95 Canadian women having difficulty deciding whether to take antidepressants in pregnancy, we compared sociodemographic factors, clinical characteristics, and treatment intent between women planning pregnancy (preconception women) and currently-pregnant women. Results About 90% of preconception women (n = 55) were married or cohabitating and university-educated, and over 60% had an annual income of > 80,000 CAD/year; this was not different from currently-pregnant women (n = 40). Almost all women had previously used antidepressants, but preconception women were more likely to report current use (85.5% vs. 45.0%). They were more likely to have high decisional conflict (83.6% vs. 60.0%) and less likely to be under the care of a psychiatrist (29.1% vs. 52.5%). Preconception women were more likely than pregnant women to report the intent to use antidepressants (60% vs. 32.5%, odds ratio 3.11, 95% confidence interval 1.33–7.32); this was partially explained by between-group differences in current antidepressant use. Conclusions Preconception women were more likely than pregnant women to intend to use antidepressants in pregnancy, in part because more of them were already using this treatment. Strategies to enhance support for decision-making about antidepressant medication use in pregnancy may need to be tailored differently for pregnancy-planning and already pregnant women.

BackgroundMajor improvements in breast cancer treatment in the last decade include advancements in postmastectomy breast reconstruction (PMBR). Unfortunately, the studies in PMBR are primarily researcher or industry led with minimal input from patients and caregivers. The aim of this study is to use the James Lind Alliance (JLA) approach to bring together the patients, caregivers and clinicians in a priority setting partnership to identify the most important unanswered research questions in PMBR.MethodsThe JLA priority setting methodology involved four key stages: gathering research questions on PMBR from patients, caregivers and clinicians; checking these research questions against existing evidence; interim prioritisation and a final consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology.ResultsIn stage 1, 3168 research questions were submitted from 713 respondents across Canada, of which 73% of the participants were patients or caregivers. Stage 2 confirmed that there were a total of 48 unique unanswered questions. In stage three, 488 individuals completed the interim prioritisation survey and the top 25 questions were taken to a final consensus meeting. In the final stage, the top 10 unanswered research questions were determined. They cover a breadth of topics including personalised surgical treatment, safety of implants and newer techniques, access to PMBR, breast cancer recurrence and rehabilitation.InterpretationIdentification of the top 10 unanswered research questions is an important first step to generating relevant and impactful research that will ultimately improve the PMBR experience for patients with breast cancer.

Background Fear of cancer recurrence (FCR) is a common concern for survivors. Oncology nurses have a unique opportunity to identify survivors at increased risk of heightened FCR. Understanding predictors of FCR would be useful for this purpose; however, results about FCR predictors are inconsistent. Objective To examine empirically inconsistent predictors of FCR as guided by Leventhal's Commonsense Model. Methods A cross-sectional survey design was used to assess FCR, sociodemographic and clinical characteristics, and characteristics of the self (self-esteem and generalized expectancies) among cancer survivors. Structural equation modeling was used to examine predictors of FCR. Results Among 1001 participants, the mean time since diagnosis was 9.07 years, and most were diagnosed with breast cancer (65.93%). The strongest predictor of higher FCR was belief that knowing someone with a recurrence affects one's own level of FCR, although knowing someone with a recurrence actually predicted lower FCR. Other significant predictors of higher FCR were having 1 or more symptoms attributed to cancer, lower self-esteem, younger age, female gender, lower pessimism, longer time since diagnosis, and active follow-up at the survivorship clinic. Conclusion Cancer survivors' perceptions are among an important series of variables that may predict higher levels of FCR. Oncology nurses are uniquely situated to identify the subset of cancer survivors with levels of FCR requiring professional intervention. Implications for practice Oncology nurses can use the predictors indicated in this study to identify survivors with greatest need for coping with FCR to facilitate expedient intervention and/or referral to psychosocial providers.

Certain subgroups of patients may be particularly vulnerable to cognitive decline after treatment with allogeneic hematopoietic stem cell transplant (HCT). The objective of this study was to identify predictors of cognitive functioning changes within the first 6 months after HCT. Fifty-eight adults treated with allogeneic HCT (53% male, mean 48 years of age) completed neuropsychological tests of learning/memory, psychomotor efficiency/processing speed, and executive functioning/working memory at three time points: pre-HCT and day 100 and 6 months post transplant. On average, there was significant improvement in learning/memory (p = 0.002), psychomotor efficiency/processing speed (p =Grade 2 was associated with worsening psychomotor efficiency/processing speed; and greater years of education predicted a faster improvement in psychomotor efficiency/processing speed. Other factors were associated with cognitive functioning over time: higher intelligence quotient (IQ) was associated with better cognitive functioning, and older age, being male, and greater pretransplant comorbidities were associated with worse cognitive functioning. Overall, cognitive performance appears to improve over the first 6 months after transplant. However, pretransplant and posttransplant factors may influence this trajectory.

Background Presentation to multidisciplinary cancer conferences (MCCs) supports optimal treatment of young women with breast cancer (YWBC). However, research shows barriers to MCC practice, and variation in professional attendance and referral patterns. A checklist may help overcome these barriers and support MCC practice with YWBC. Methods We developed, piloted and evaluated an MCC checklist in sites participating in a pan-Canadian study (RUBY; Reducing the bUrden of Breast cancer in Young women). A survey assessed checklist processes and impacts, and checklist data were analysed for checklist uptake, MCC presentation rates and MCC processes including staff attendance. Results Fifteen RUBY sites used the checklist (~50%), mostly for data collection/tracking. Some positive effects on clinical practice such as increased presentation of YWBC at MCC were reported, but most survey participants indicated that MCC processes were sufficient without the checklist. Conversely, checklist data show that only 31% of patients were presented at MCC. Of those, 41% were recommended treatment change. Conclusion Despite limited checklist uptake, there was evidence of its clinical practice benefit. Furthermore, it supported data collection/quality monitoring. Critically, checklist data showed gaps in MCC practice and low MCC presentation rates for YWBC. This contrasts with overall provider perceptions that MCCs are working well. Findings suggest that supports for MCC are needed but may best take the form of clear national practice recommendations and audit and feedback cycles to inform awareness of good MCC practice and outcomes. In this setting, tools like the MCC checklist may become helpful in supporting MCC practice.

Background Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. Methods We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. Results Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. Conclusions In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.

Background Decisions about antidepressant use in pregnancy are complex. We performed a pilot randomized controlled trial assessing the feasibility of a trial protocol for an online patient decision aid (PDA) for women deciding about antidepressant use in pregnancy. Methods 96 preconception and pregnant Canadian women recruited from specialist (n = 51) and non-specialist (n = 45) settings with Decisional Conflict Scale (DCS, range 0–100) score of ≥25 signifying moderate-to-high decisional conflict were randomly allocated to either the PDA or a control condition that guided participants to publicly available resources for advice around antidepressants and pregnancy. Follow-up data were collected at 4 weeks post-randomization. Results About 88.9% of eligible participants consented to participate. Women's views of the tool were positive; 88.7% of participants provided follow-up data. At follow-up, mean DCS score had decreased by 19.9 points in the PDA group vs. 13.3 in controls (adjusted mean difference, MD, 7.01, 95% CI −14.3 to 0.30). In the non-specialist setting, DCS scores decreased more for PDA users (25.5 points) than controls (10.5 points; adjusted MD −15.1, 95% CI −25.6 to −4.55); the MD was negligible in the specialist setting. Limitations The main limitation is the highly educated, high-income nature of our sample. Conclusions Evaluation of an online PDA for antidepressant use in pregnancy with national recruitment is feasible. Pilot results suggest that the tool is acceptable and reduces decisional conflict more than clinical care alone in a non-specialist setting. Evaluation of the PDA's impact on longer-term maternal and child clinical outcomes is a key next step.

Background Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017). Methods Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries. Subjects completed a questionnaire at the time of genetic testing, which included past use of cancer prevention options and screening tests. Biennial follow-up questionnaires were administered. Results Six-thousand two-hundred and twenty-three women were followed for a mean of 7.5 years. The mean age at last follow-up was 52.1 years (27–96 years) and 42.3% of the women had a prior diagnosis of breast cancer. In all, 27.8% had a prophylactic bilateral mastectomy and 64.7% had a BSO. Screening with breast MRI increased from 70% before 2009 to 81% at or after 2009. There were significant differences in uptake of all options by country. Conclusion For women who received genetic testing more recently, uptake of prophylactic mastectomy and breast MRI is significantly higher than those who received genetic testing more than 10 years ago. However, uptake of both BSO and breast MRI is not optimal, and interventions to increase uptake are needed.

Simple Summary The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Study subjects registered online and were sent a saliva sample kit. Of the 1269 tested individuals between March 2017 and January 2019, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. The study results endorse a model where genetic testing is offered directly to the consumer via a home-delivered kit and a saliva sample, and some clinical guidance for those with positive test results. We believe that testing has substantial benefits, and therefore, we would like to expand testing to as many eligible women as possible. Abstract There is limited information of the outcomes of direct-to-consumer testing for BRCA1 and BRCA2 mutations. The Screen Project was initiated in 2017 to offer BRCA1 and BRCA2 genetic screening to all Canadians over the age of 18 who wish to know their mutation status. Patients enrolled in the study from 2017 to 2019 and were followed for one year after the receipt of a genetic test result. Study subjects registered online and were sent a saliva sample kit, which was shipped to the reference laboratory. Pre-test genetic counselling and counselling for mutation-negative subjects was optional and at the individual’s discretion. There were 1269 tested individuals between March 2017 and January 2019. A total of 1157 (93%) were women and 87 (7%) were men. Sixty-six percent had a first- or second-degree relative with breast or ovarian cancer. Of the 1269 tested individuals, 30 (2.4%) had a pathogenic mutation in BRCA1 or BRCA2 (20 women and 10 men). Seventy-five percent of the female mutation carriers underwent a bilateral mastectomy and/or salpingo-oophorectomy within a year of receiving a positive result. Genetic counselling was available at no cost to all participants but was requested by only 5% of the non-carriers. The study subjects expressed a high degree of satisfaction with the process.

Objective To summarize the evidence regarding the accuracy of continuous non-invasive arterial pressure measurements in adult critical care patients. Research methodology Medline, EMBASE, and CINAHL were searched for studies that included adult critical care patients reporting the agreement between continuous non-invasive and invasive arterial pressure measurements. The studies were selected and assessed for risk of bias using the Revised Quality Assessment of Diagnostic Accuracy Studies tool by two independent reviewers. The Grading of Recommendations, Assessment, Development and Evaluations approach was used. Pooled estimates of the mean bias and limits of agreement with outer 95% confidence intervals (termed population limits of agreement) were calculated. Results Population limits of agreement for systolic blood pressure were wide, spanning from −36.13 mmHg to 28.28 mmHg (18 studies; 785 participants). Accuracy of diastolic blood pressure measurements was highly inconsistent across studies, resulting in imprecise estimates for the population limits of agreement. Population limits of agreement for mean arterial pressure spanned from −39.96 mmHg to 44.36 mmHg (17 studies; 765 participants). The evidence was rated as very low-quality due to very serious concerns about heterogeneity and imprecision. Conclusion Substantial differences in blood pressure were identified between measurements taken from continuous non-invasive and invasive monitoring devices. Clinicians should consider this broad range of uncertainty if using these devices to inform clinical decision-making in critical care.

BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56).CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

BACKGROUND Whether to undergo postmastectomy breast reconstruction (PMBR) is a challenging, preference-sensitive decision. It is therefore paramount to optimize decision quality through ensuring patients' knowledge and aligning treatments with their personal preferences. This study assessed the effects of a preconsultation educational group intervention (PEGI) on patient knowledge, state-trait anxiety, and decisional conflict (patient uncertainty in decision making) during the decision-making process. METHODS This phase 3 randomized controlled trial assessed effects of a PEGI in women without active breast cancer undergoing delayed PMBR, or prophylactic mastectomy with immediate PMBR. Both groups underwent routine education before consultation. In addition, the intervention group underwent a PEGI composed of presentations from a plastic surgeon and nurse, a value clarification exercise, and shared experiences from PMBR patients before the consultation with the plastic surgeon. Before and 1-week after consultation, outcome measures were assessed using the Decisional Conflict Scale, State-Trait Anxiety Inventory, and the BREAST-Q. RESULTS Of the 219 women deemed eligible, a total of 156 women were recruited and randomized. Treatment fidelity was 96% and retention was 88%. At baseline, there were no significant differences in terms of demographic or clinical status, knowledge, state-trait anxiety, and decisional conflict. Patient knowledge about PMBR improved in both groups; however, the degree of knowledge attainment was significantly greater in the PEGI group (24.5% improvement in the intervention group compared with 13.5% in the routine education group, P < 0.001). The reduction in decisional conflict from baseline to follow-up was greater in the intervention group compared with the routine education; however, the difference only approached significance (P = 0.09). CONCLUSIONS The provision of a preconsultation educational group intervention has been shown to significantly close the knowledge gap on PMBR in patients seeking delayed breast reconstruction or prophylactic mastectomy with immediate breast reconstruction compared with routine education alone.

Background Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with BRCA mutations and measured choices and sequence of breast cancer risk reduction strategies. Methods Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women’s recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices. Results Among 598 respondents, mean age was 40.9 years (range 25–55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen. Conclusions Women revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with BRCA1 or BRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.

This study aimed to evaluate the impact of rapid genetic testing (RGT) for BRCA1 and BRCA2 at the time of breast cancer diagnosis on treatment choices. Bilateral mastectomy for the treatment of breast cancer in women with a BRCA1 or BRCA2 mutation offers a reduction in the risk of contralateral breast cancer. It is unclear whether offering RGT at the time of breast cancer diagnosis has an impact on women’s surgical decision-making. Women with breast cancer diagnosed between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. The participants completed a questionnaire before genetic testing, then one week and one year after disclosure of the genetic test result. Before surgery, RGT was performed. Diagnostic, pathologic, and treatment data were compared between those with and those without a BRCA mutation. The study enrolled 1007 women who consented to RGT. The mean age of the participants was 46.3 years, and the median time to result disclosure was 10 days. A BRCA mutation was found in 6% of the women. The women with a BRCA mutation were significantly more likely to elect for bilateral mastectomy than the women without a BRCA mutation (p

Women with a germline pathogenic variant in the BReast CAncer susceptibility genes (BRCA1 or BRCA2) have an increased risk of early-onset breast and ovarian cancer. In addition to weighing cancer screening and risk-reduction options, healthy BRCA mutation carriers of childbearing age may choose to preclude passing the mutation to the next generation. In the current study, we report on preimplantation genetic diagnosis (PGD) practices in BRCA-positive Israeli women who were offered PGD at no cost. Methods: we measured PGD uptake, decision satisfaction or regret, and predictors of uptake. Of the 70 participant female carriers, only 25.7% chose to use PGD to prevent transmission of the mutation, and were not predicted by age or religious affiliation. For those who chose IVF/PGD, satisfaction with the decision regarding IVF and PGD was significantly higher than those who did not have IVF and PGD (p

The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR.The DA was developed and evaluated in three phases. The first phase included the development of the DA with input and review by practitioners and key stakeholders. The second phase involved pilot testing of the feasibility and acceptability of the DA with a convenience sample of women with delayed PMBR. The third phase involved a pretest/post-test evaluation of the DA for women who were making decisions about their PMBR options.The DA was developed using the Ottawa Decision Support Framework. In the second phase of the study, 21 women completed the acceptability survey, of whom 100% reported that they would recommend the DA to other women. In the third phase, decisional conflict decreased significantly (p 0.001) and knowledge increased significantly (p 0.001) from prior to using the DA to 1-2 weeks after using the DA.The DA is feasible and acceptable to women considering delayed PMBR. Furthermore, the DA is effective at reducing decisional conflict and increasing knowledge about delayed PMBR. The DA is an appropriate tool to be used in addition with standard care in women considering PMBR.

162 Background: Young women with breast cancer (YWBC) have unique survivorship needs due to life stage at point of diagnosis. Peer support sought by YWBC through social media channels appears to be rising. We aimed to understand the unmet needs of YWBC in order to develop a tailored peer support program to improve young women’s breast cancer experience and ultimately reduce psychosocial morbidity long-term. Methods: Using qualitative inquiry, we conducted semi-structured interviews with YWBC survivors and clinicians using purposive sampling. Inclusion criteria were women aged 40 years or younger at diagnosis, stage 0-IV disease. Survivors were minimum one year post-diagnosis and with active treatment complete. Interviews were recorded and transcribed verbatim and data was analyzed using Thorne’s Interpretive Description. Themes were reviewed with study team throughout data analysis. Results: Thirty-six participants were interviewed from ten centers across seven Canadian provinces; mean age 36 years. Participant reported demographics:18% ‘visible minority’, 9% ‘born outside Canada’, 7% ‘Indigenous’ and 54% of patients’ household income at or below Canadian average. At point of diagnosis 69% married, 44% had children and 9% pregnant or postpartum. Themes from YWBC interviewed focused on coping needs: feeling alone, misunderstood by professionals and misplaced among peers. Participants described all-age peer support groups risked triggering anxieties, lacked convenience and were comprised of women at later life stages with differing needs. YWBC reported lack of young age breast cancer-specific peer support. YWBC frequently found support through social media de novo, by following young-age breast cancer survivor pages, blogs and forums as well as virtual support groups. YWBC also report benefit from identifying similar life and cancer stage survivors globally and forming individual relations virtually, through direct messaging. Additionally, benefits described from age-specific social media support included unique shared experience and understanding, hope from positive outcomes of similar life stage diagnoses, and increased confidence and healthcare navigation for YWBC. Women unanimously requested one on one peer support program development - a survivor mentorship scheme specifically for YWBC that would provide the convenience of online support without the obligations or emotionally overwhelming nature of structured support groups. Conclusions: We have identified unique support needs from this young cohort of women that are not currently being met within standard Canadian healthcare pathways. We aim to develop a novel one on one peer support program for YWBC, to optimize psychosocial support and improve young women’s empowerment and autonomy in managing the effects of cancer long-term.

Multidisciplinary genetic clinics offer counseling and testing to those who meet criteria for familial breast cancer, and plastic surgeons become integral to this process when risk-reducing surgery and postmastectomy reconstruction are deemed appropriate. As reconstructive surgeons, it is important that plastic surgeons are aware of the risks and issues associated with the genetic variants that cause patients to present for prophylactic or therapeutic surgery.

Purpose Unaffected women who carry BRCA1 or BRCA2 mutations face difficult choices about reducing their breast cancer risk. Understanding their treatment preferences could help us improve patient counseling and inform drug trials. The objective was to explore preferences for various risk-reducing options among women with germline BRCA1/2 mutations using a discrete-choice experiment survey and to compare expressed preferences with actual behaviors. Methods A discrete-choice experiment survey was designed wherein women choose between hypothetical treatments to reduce breast cancer risk. The hypothetical treatments were characterized by the extent of breast cancer risk reduction, treatment duration, impact on fertility, hormone levels, risk of uterine cancer, and ease and mode of administration. Data were analyzed using a random-parameters logit model. Women were also asked to express their preference between surgical and chemoprevention options and to report on their actual risk-reduction actions. Women aged 25–55 years with germline BRCA1/2 mutations who were unaffected with breast or ovarian cancer were recruited through research registries at five clinics and a patient advocacy group. Results Between January 2015 and March 2016, 622 women completed the survey. Breast cancer risk reduction was the most important consideration expressed, followed by maintaining fertility. Among the subset of women who wished to have children in future, the ability to maintain fertility was the most important factor, followed by the extent of risk reduction. Many more women said they would take a chemoprevention drug than had actually taken chemoprevention. Conclusions Women with BRCA1/2 mutations indicated strong preferences for breast cancer risk reduction and maintaining fertility. The expressed desire to have a safe chemoprevention drug available to them was not met by current chemoprevention options. Electronic supplementary material The online version of this article (doi:10.1007/s10549-017-4332-3) contains supplementary material, which is available to authorized users.

Women with a BRCA1 or BRCA2 mutation are at high risk for breast cancer and must make important decisions about breast cancer prevention and screening. In the current study, we report a multisite, randomized, controlled trial evaluating the effectiveness of a decision aid for breast cancer prevention in women with a BRCA mutation with no previous diagnosis of cancer. Within 1 month of receiving a positive BRCA result, women were randomized to receive either usual care (control group) or decision aid (intervention group). Participants were followed at 3, 6, and 12 months; were asked about preventive measures; and completed standardized questionnaires assessing decision making and psychosocial functioning. One hundred fifty women were randomized. Mean cancer-related distress scores were significantly lower in the intervention group compared with the control group at 6 months (P = 0.01) and at 12 months postrandomization (P = 0.05). Decisional conflict scores declined over time for both groups and at no time were there statistical differences between the two groups. The decision aid for breast cancer prevention in women with a BRCA1 or BRCA2 mutation is effective in significantly decreasing cancer-related distress within the year following receipt of positive genetic test results. Genet Med 19 3, 330–336.

This abstract was withdrawn by the authors.

Background Delayed breast reconstruction is an option for women who have undergone mastectomy; however, uptake is low. The purpose of this study was to identify premastectomy and postmastectomy demographic, clinical, and psychosocial predictors of uptake of delayed breast reconstruction in the long-term survivorship period. Methods This was a prospective longitudinal survey study of mastectomy patients in which a repeated measures design was used to evaluate uptake of delayed breast reconstruction. Demographic, clinical, and psychosocial variables were collected before mastectomy and 1 year after mastectomy. Information regarding uptake of delayed breast reconstruction was collected at approximately 6 years after mastectomy. A predictive model was designed using a multivariate logistic regression model and Akiake information criterion stepwise algorithm. Results Ninety-six mastectomy patients were followed from before mastectomy to 75.2 months after mastectomy, and 35 women (36.5 percent) underwent delayed breast reconstruction. Women who elected for delayed breast reconstruction experienced worsening of body concerns from before mastectomy to 1 year after mastectomy, compared with women who did not elect to undergo delayed breast reconstruction (p = 0.03). Mean scores for psychological distress were significantly worse both before mastectomy and 1 year after mastectomy in women who went on to undergo delayed breast reconstruction compared with those who did not undergo delayed breast reconstruction (p = 0.034 and p = 0.022, respectively). A predictive model for the uptake of delayed breast reconstruction was developed using demographic, clinical, and psychosocial characteristics. The area under the receiver operating characteristic curve was 85 percent, indicating good precision. Conclusions Women who are experiencing higher levels of distress, anxiety, and body concerns both before and after mastectomy appear to be significantly likely to select delayed breast reconstruction. This may have implications for postreconstruction satisfaction and psychosocial functioning. Clinical question/level of evidence Risk, III.

Aim To identify and assess the quality of decision aids that align the decision, values and information provided for parents making end-of-life or palliative care decisions for children with life-threatening conditions. Methods Six databases and the grey literature were searched in December 2018. Two reviewers independently reviewed database citations, and one reviewed grey literature citations. Citation chaining via Scopus was conducted. Quality was assessed using IPDAS Collaboration Criteria. Results After reviewing 18 671 database citations and 10 988 grey literature citations, 18 citations describing 11 decision aids remained. Decision aids targeted premature infants, children requiring airway management, children with cancer and children with scoliosis. Three aids underwent testing beyond initial development. Quality scores averaged 27 of 50 points. Conclusions There are few high-quality decision aids available for use and a lack evidence of widespread clinical use. Additional research is needed to support systematic development and the use of decision aids with families.

Background Premenopausal breast cancer patients are at risk of treatment-related infertility. Many patients do not receive sufficient fertility information before treatment. As such, our team developed and alpha tested the Begin Exploring Fertility Options, Risks, and Expectations decision aid (BEFORE DA). Methods The BEFORE DA development process was guided by the International Patient Decision Aids Standards and the Ottawa Decision Support Framework. Our team used integrated knowledge translation by collaborating with multiple stakeholders throughout the development process including breast cancer survivors, multi-disciplinary health care providers (HCPs), advocates, and cancer organization representatives. Based on previously conducted literature reviews and a needs assessment by our team – we developed a paper prototype. The paper prototype was finalized at an engagement meeting with stakeholders and created into a graphically designed paper and mirrored online decision aid. Alpha testing was conducted with new and previously engaged stakeholders through a questionnaire, telephone interviews, or focus group. Iterative reviews followed each step in the development process to ensure a wide range of stakeholder input. Results Our team developed an 18-page paper prototype containing information deemed valuable by stakeholders for fertility decision-making. The engagement meeting brought together 28 stakeholders to finalize the prototype. Alpha testing of the paper and online BEFORE DA occurred with 17 participants. Participants found the BEFORE DA usable, acceptable, and most provided enthusiastic support for its use with premenopausal breast cancer patients facing a fertility decision. Participants also identified areas for improvement including clarifying content/messages and modifying the design/photos. The final BEFORE DA is a 32-page paper and mirrored online decision aid (https://fertilityaid.rethinkbreastcancer.com). The BEFORE DA includes information on fertility, fertility options before/after treatment, values clarification, question list, next steps, glossary and reference list, and tailored information on the cost of fertility preservation and additional resources by geographic location. Conclusion The BEFORE DA, designed in collaboration with stakeholders, is a new tool for premenopausal breast cancer patients and HCPs to assist with fertility discussions and decision-making. The BEFORE DA helps to fill the information gap as it is a tool that HCPs can refer patients to for supplementary information surrounding fertility.

BACKGROUND The rates of contralateral prophylactic mastectomy (CPM) are increasing in women with breast cancer. Previous retrospective research has examined clinical and demographic predictors of the uptake of CPM. However, to the authors' knowledge, there has been very little prospective research to date that has examined psychosocial functioning prior to breast cancer surgery to determine whether psychosocial functioning predicts uptake of CPM. The current study was conducted to evaluate demographic, clinical, and psychosocial predictors of the uptake of CPM in women with unilateral breast cancer without a BRCA1 or BRCA2 mutation. METHODS Women with unilateral non-BRCA-associated breast cancer completed questionnaires prior to undergoing breast cancer surgery. Participants completed demographic and psychosocial questionnaires assessing anxiety, depression, cancer-related distress, optimism/pessimism, breast satisfaction, and quality of life. Pathological and surgical data were collected from medical charts. RESULTS A total of 506 women consented to participate, 112 of whom (22.1%) elected to undergo CPM. Age was found to be a significant predictor of CPM, with younger women found to be significantly more likely to undergo CPM compared with older women (P

Importance Rates of bilateral mastectomy continue to increase in average-risk women with unilateral in situ and invasive breast cancer. Contralateral prophylactic mastectomy rates increased from 5% to 12% of all operations for breast cancer in the US from 2004 to 2012. Among women having mastectomy, rates of contralateral prophylactic mastectomy have increased from less than 2% in 1998 to 30% in 2012. Observations The increased use of breast magnetic resonance imaging and genetic testing has marginally increased the number of candidates for bilateral mastectomy. Most bilateral mastectomies are performed on women who are at no special risk for contralateral cancer. The true risk of contralateral breast cancer is not associated with the decision for contralateral prophylactic mastectomy; rather, the clinical factors associated with the probability of distant recurrence are associated with bilateral mastectomy. Several changes in society and health care delivery appear to act concurrently and synergistically. First, the anxiety engendered by a fear of cancer recurrence is focused on the contralateral cancer because this is most easily conceptualized and provides a ready target that can be acted upon. Second, the modern woman with breast cancer is supported by the surgeon and the social community of breast cancer survivors. Surgeons want to respect patient autonomy, despite guidelines discouraging bilateral mastectomy, and most women have their expenses covered by a third-party payer. Satisfaction with the results is high, but the association with improved psychosocial well-being remains to be fully understood. Conclusions and Relevance Reducing the use of medically unnecessary contralateral prophylactic mastectomy in women with nonhereditary, unilateral breast cancer requires a social change that addresses patient-, physician-, cultural-, and systems-level enabling factors. Such a transformation begins with educating clinicians and patients. The concerns of women who want preventive contralateral mastectomy must be explored, and women need to be informed of the anticipated benefits (or lack thereof) and risks. Areas requiring further study are considered.

568 Background: In breast cancer, clinicians aim to improve survival while patients value quality of life. We aim to delineate the impact of patient, tumour and treatment factors on psychosocial outcomes after treatment. Methods: A prospective cohort of women with unilateral stage I-III breast cancer were recruited at University Health Network in Toronto, Canada between 2014-2017. Validated questionnaires (BREAST-Q, Impact of Event, Hospital Anxiety & Depression Scales) were completed pre-operatively, and 6 and 12 months after surgery. Change in psychosocial scores over time by surgical procedure was assessed using linear mixed models, controlling for age, pathologic stage, hormone (HR) and HER2 receptor, and treatments. Predictors of psychosocial outcomes at 12 months were assessed using multivariable linear regression models. P values

Simple Summary Women with a BRCA1 or BRCA2 mutation are at an increased risk of developing hereditary breast and ovarian cancers. While genetic counselling by genetic counsellors takes place before and after receiving the results of genetic testing, genetic counsellors are not involved in the patient’s long-term psychosocial follow-up. Genetic testing can cause short-term and long-term distress in women with a BRCA1 or BRCA2 mutation, and follow-up supports may be necessary for some women. As the uptake of genetic testing for hereditary breast and ovarian cancer increases, the need for additional sources of support may be needed. This review examined the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Abstract This scoping review aimed to explore the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Four electronic bibliographic databases were searched. After review, 23 articles that described or assessed forms of an additional psychosocial intervention for individuals with a BRCA mutation were identified and included. Intervention types discussed in the articles were telephone-based peer-to-peer counselling (5), online communities (4), in-person group counselling (8), and one-day sessions (6). Outcomes investigated within the articles included psychosocial outcomes (18), satisfaction (8), health behaviours (7), and knowledge (5). The included studies suggested that telephone-based peer-to-peer counselling and online communities improve patient knowledge and psychosocial functioning and can overcome challenges such as scheduling and travel associated with in-person support groups, but may have challenges with recruitment and retainment of participants. Group in-person education sessions satisfied the need amongst BRCA1/2 carriers in terms of accessing necessary information regarding cancer risk assessment and management; however, the impact of group education sessions on psychological outcomes was variable across the included studies. Overall, all the forms of intervention described in this scoping review were well-received by participants; some have been shown to reduce distress, depression, and anxiety.

Although neurocognitive impairment has been established as a major issue among cancer survivors, the real-world consequences of this impairment are unclear. This study investigated the relationship between neurocognitive functioning and medication management ability over time among 58 patients treated with allogeneic hematopoietic stem cell transplantation (HCT). Participants completed a neuropsychological test battery and a simulated medication management task at three time points: pre-transplant (T0), Day 100 (T1) and 6 months post transplant (T2). Neurocognitively impaired participants performed worse on the medication management task than neurocognitively normal participants at each time point, and were more likely to score in the impaired range of medication management ability post transplant (72% vs 20%, P

Background: Distress levels among female BRCA1 and BRCA2 mutation carriers can be similar to levels reported among breast cancer patients. However, there is a lack of data on long-term psychosocial functioning, and it is not known if uptake of risk-reducing surgery influences long-term cancer related distress in women with a BRCA mutation who are unaffected with cancer. The objective of this study was to evaluate long-term cancer-related distress in women with a BRCA mutation, and to evaluate predictors of distress, including uptake of cancer risk reducing surgery. Methods: Female BRCA1 or BRCA2 mutation carriers, ages 25-55, and without cancer were eligible to complete the survey online. A validated instrument, Impact of Events Scale (IES)-Revised (Horowitz 1979, Weis & Marmar 1995; 0-80 overall scale), was used to assess current levels of cancer risk-related psychological distress. Respondents were recruited through the Facing Our Risk of Cancer Empowered (FORCE) advocacy organization, which includes women at high risk of breast cancer. This interim analysis is part of a larger multi-center patient preference study of BRCA mutation carriers designed to assess women's willingness to adopt hypothetical treatments to prevent breast cancer. Linear regression was used to evaluate predictors of IES distress levels. Results: Between January and April 2015, 259 women completed the survey. The mean age of the participants was 41 years, and the mean time since receipt of genetic test results was 3.5 years (range 0-16; median 2 years). One hundred thirty-six (52%) women elected for prophylactic bilateral mastectomy (PBM), 139 (54%) elected for bilateral salpingo oophorectomy (BSO) (93 [36%] women had both surgeries), and 77 (30%) had not undergone risk-reducing surgery. The mean total IES score was 15.1 (range 0-72; median 11). Overall, 54 (21%) women reported moderate or severe cancer-related distress, and those who had undergone risk-reducing surgery reported lower perceived risk of developing breast cancer. Results to date indicate that shorter time since notification of mutation status, not having PBM (with or without BSO) (table), and not completing post-secondary education were independent predictors of higher IES distress scores. IES severityNo prophylactic surgeryPBM onlyBSO onlyPBM and BSOn (%)77434693Subclinical27 (35)23 (54)16 (35)44 (47)Mild26 (34)13 (30)21 (46)35 (38)Moderate18 (23)5 (12)6 (13)11 (12)Severe6 (8)2 (5)3 (6)3 (3) Conclusions: This study measured cancer-related distress in a large population of women with BRCA mutations who participate in the FORCE online support community. Higher levels of distress were associated with not having PBM and more recent genetic test disclosure. These findings are specific to a more informed community of women with high levels of understanding of cancer risk than may be seen in the clinical setting. Citation Format: Liede A, Fairchild A, Friedman S, Amelio J, Hallett DC, Mansfield CA, Metcalfe KA. Risk-reducing surgery and cancer-related distress among female BRCA1 and BRCA2 mutation carriers. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-09.

570 Background: Rates of bilateral mastectomy continue to rise in average-risk women with unilateral breast cancer. We aim to characterize psychosocial predictors of surgical procedure and how psychosocial outcomes change over time after surgery for breast cancer. Methods: A prospective cohort of women with unilateral, nonhereditary breast cancer were recruited at University Health Network in Toronto, Canada between 2014-2017. Women completed validated psychosocial questionnaires (BREAST-Q) pre-operatively, and 6 and 12 months after surgery. Outcomes were assessed between three surgical groups (unilateral lumpectomy, unilateral mastectomy, bilateral mastectomy). Predictors of surgical procedure were identified using a multinomial logistic regression model. Change in psychosocial scores over time according to procedure was assessed using linear mixed models. All models control for age, stage, reconstruction and treatment. P values < .05 were considered statistically significant. Results: 506 women underwent surgery as follows: 216 unilateral lumpectomy (43%), 181 unilateral mastectomy (36%) and 109 bilateral mastectomy (22%). In the multinomial regression model, younger age (p < .01), and lower chest physical (p = .03) and sexual well-being (p = .02) predicted having bilateral mastectomy over unilateral lumpectomy while younger age (p < .01) and lower disease stage (p = .02) predicted bilateral mastectomy over unilateral mastectomy. The mixed model demonstrates that breast satisfaction follows a non-linear pattern of change over time, with 6- but not 12-month scores being significantly different from baseline (p = .015). Procedure predicts baseline satisfaction (p = .016), with bilateral mastectomy having worse satisfaction than unilateral lumpectomy. Procedure also predicts change in satisfaction, with unilateral and bilateral mastectomy having lower scores across time than lumpectomy. While a significant improvement in psychological well-being is detected by 12 months (p = .02), those with unilateral and bilateral mastectomy have worse psychological well-being over time compared to lumpectomy. Women having mastectomy start with worse physical well-being than those in the lumpectomy group, but their physical well-being does not decline as much as the lumpectomy group over time (p < .01). Conclusions: Definitive surgical procedure affects the trajectory of psychosocial functioning over time. This emerging data may be used to further facilitate surgical decision-making in women considering contralateral prophylactic mastectomy.

Prophylactic bilateral salpingo-oophorectomy (BSO) is recommended at an early age to BRCA mutation carriers to prevent ovarian cancer. It is critical to evaluate the impact of BSO on non-cancer outcomes, including quality of life (QOL), menopausal symptoms and sexual functioning.BRCA mutation carriers who elected to undergo a BSO completed three questionnaires prior to surgery and then again approximately one and three years following surgery which included: 1) medical history questionnaire, 2) Menopause-Specific Quality of Life Intervention questionnaire and 3) Sexual Activity Questionnaire. The change in quality of life, menopausal symptoms and sexual functioning before and after oophorectomy was determined using a paired t-test and stratified by menopausal status at surgery.We included 140 BRCA mutation carriers with an average follow-up of 3.5 years following BSO. Among 93 women who were premenopausal, oophorectomy was associated with an increase in menopausal symptoms (vasomotor, physical) (P 0.001) and a decline in sexual functioning (discomfort, pleasure) (P ≤ 0.0001), but had no impact on overall QOL (P = 0.31). HRT mitigated, but did not eliminate the adverse effects. Women who were postmenopausal at surgery (n = 47) experienced an increase in physical symptoms (P = 0.03) and a decline in sexual functioning (discomfort) (P = 0.004) and in overall QOL (P = 0.04).This study demonstrates that 3.5 years after oophorectomy, BRCA mutation carriers experience a significant worsening of menopausal symptoms and a decline in sexual functioning, particularly among those who underwent surgery prior to natural menopause. The use of HRT mitigated some but not all the effects. Overall, women who were premenopausal at surgery did not experience a decline in their QOL.

To compare psychosocial function outcomes in early breast cancer patients treated with breast-conserving surgery (BCS), mastectomy alone (MA), and mastectomy with immediate breast reconstruction (IBR) at 1 year after surgery.Early-stage (stage 0-2) breast cancer patients treated with BCS, MA, and IBR at the University Health Network, Toronto, Ontario, Canada between May 1 2015 and July 31 2016 were prospectively enrolled. Their changes in psychosocial functioning from baseline to 12 months following surgery were compared by using the BREAST-Q, Hospital Anxiety and Depression Scale, and Impact of Event Scale with ANOVA and linear regression.There were 303 early-stage breast cancer patients: 155 underwent BCS, 78 MA, and 70 IBR. After multivariable regression accounting for age, baseline score, income, education, receipt of chemoradiation or hormonal therapy, ethnicity, cancer stage, and unilateral versus bilateral surgery, breast satisfaction was highest in BCS (72.1, SD 19.6), followed by IBR (60.0, SD 18.0), and MA (49.9, SD 78.0) at 12 months, p 0.001. Immediate breast reconstruction had similar psychosocial well-being (69.9, SD 20.6) compared with BCS (78.5, SD 20.6), p = 0.07. Sexual and chest physical well-being were similar between IBR, BCS, and MA, p 0.05.Our study found that in a multidisciplinary breast cancer centre where all three breast ablative and reconstruction options are available to early breast cancer patients, either BCS or IBR can be used to provide patients with a higher degree of satisfaction and psychosocial well-being compared with MA in the long-term.

Background To evaluate the predictors of mortality, including ER status, in women with a BRCA2 mutation and breast cancer. Methods Eligible participants were identified from within two longitudinal cohorts. These patients were selected because they were diagnosed with breast cancer between 1975 and 2015 and carried a BRCA2 mutation. Data were abstracted from the medical record and pathology report. We analysed the effects of ER status and other variables on breast cancer specific survival using a Cox proportional hazards model. Results Three hundred ninety women with breast cancer and a BRCA2 mutation were included in the analysis. The mean follow-up time was 12.3 years (range 1–39 years) and 89 subjects died (22.8%). In the multivariate analysis, women with ER-positive tumours were more likely to die than women with ER-negative tumours (HR 2.08, 95% CI 0.99–4.36, p = 0.05), and this was of borderline significance. For the 233 women with ER-positive tumours the 20-year survival rate was 62.2%, compared to 83.7% for 58 women with ER-negative tumours (p = 0.03). Conclusions The majority of women with a BRCA2 mutation present with ER-positive breast cancer, and for these women, prognosis may be worse than for BRCA2 carriers with ER-negative breast cancer.

In 2001, genetic testing for BRCA1 and BRCA2 was introduced in Ontario, for women at high-risk of breast or ovarian cancer. To date over 30,000 individuals have been tested throughout Ontario. Testing was offered to all Ontario residents who were eligible under any of 13 criteria. We report the results of tests conducted at Mount Sinai Hospital from 2007 to 2014. A total of 4726 individuals were tested, 764 (16.2%) were found to carry a pathogenic variant (mutation). Among 3684 women and men who underwent testing without a known familial BRCA mutation, 331 (9.0%) were found to carry a mutation. Among 1042 women and men tested for a known family mutation, 433 (41.6%) were positive. There were 603 female mutation carriers, of these, 303 were affected with breast or ovarian cancer (50%) and 16 with another cancer (2.3%). Of 284 unaffected female carriers, 242 (85%) were tested for a known family mutation and 42 (15%) were the first person in the family to be tested. By placing greater emphasis on recruiting unaffected female relatives of known mutation carriers for testing, greater than one-half of newly identified carriers will be unaffected.

Background. Patient decision aids (PtDAs) supplement advice from health care professionals by communicating the absolute risk or benefit of treatment options (i.e., X/100). As such, PtDAs have been amenable to binary outcomes only. We aimed to develop and test the validity of the Conversion to Risk Estimates through Application of Normal Theory (CREATE) method for estimating absolute risk based on continuous outcome data. Methods. CREATE is designed to derive an estimate of the proportion of those who experience a clinically relevant degree of change (CRDoC). We used a 2-stage validation process using real and simulated change score data, respectively. First, using raw data from published intervention trials, we calculated the proportion of patients with a CRDoC and compared that with our CREATE-derived estimate using chi-square tests of association. Second, 200,000 simulated distributions of change scores were generated with widely varying distribution characteristics. Actual and CREATE-derived estimates were compared for each simulated distribution, and relative differences were summarized graphically. Results. The absolute difference between the estimated and actual CRDoC did not exceed 5% for any of the samples based on real data. Applying the CREATE method to 200,000 simulated scenarios demonstrated that the CREATE method should be avoided for outcomes where the underlying distribution can be reasonably assumed to have high levels of skew or kurtosis. Conclusion. Our results suggest that standard statistical theory can be used to estimate continuous outcomes in absolute terms with reasonable accuracy for use in PtDAs; caution is advised if outcome summary statistics are assumed to have been derived from highly skewed distributions.

Introduction: Patients with Turner syndrome demonstrate a variety of breast deformities that can contribute to their reported lack of self-esteem, sexual health and social adjustment. Breast reconstruction is an option for women with TS to correct breast deformities. Methods: We present three cases of women with Turner syndrome referred to the Breast Cancer Clinic at Women's College Hospital in Toronto between 1996 and 2009. Each woman had a breast deformity despite being on hormone replacement therapy and was requesting reconstruction to increase their self-esteem, feelings of femininity and sexual confidence. Results: Women with Turner syndrome may present with various breast deformities, including tubular deformities, bilateral developmental mammary hyperplasia, hypoplasia and asymmetry. Pre-operative self-ratings of breast appearance ranged from 3 to 6 (1 = hate, 10 = love). All patients reported breast deformities as having negative effect on self-esteem. All patients received bilateral implant reconstruction resulting in an improved self-rating of breast appearance. Conclusions: Women with Turner syndrome and breast deformities may benefit from bilateral breast reconstruction.

The purpose of this study is to determine the prevalence of PALB2 mutations among breast cancer families from the United States. The PALB2 gene was screened for mutations in 90 familial breast cancer patients from the Creighton University Breast Cancer Family Registry. These patients had previously tested negative for mutations in BRCA1 and BRCA2. Two of 90 breast cancer patients (2.2 %) were found to carry a truncating mutation in PALB2 (c.2411_2412delCT and c.2053delC). Both probands were diagnosed with breast cancer before age 35 and each had three relatives with breast cancer. Mutations in PALB2 are less common than BRCA1 and BRCA2 in familial breast cancer patients. However, testing for PALB2 mutations is a useful adjunct for patients undergoing testing for BRCA1 and BRCA2.

The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least 1 first-degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age- and gene-specific breast cancer rates were calculated. The relative risks of breast cancer for subjects with a family history of breast cancer, compared to no family history were calculated. The mean age at baseline was 41.1 years, and they were followed for a mean of 6.0 years. The estimated penetrance of breast cancer to age 80 years was 60.8% for BRCA1 and 63.1% for BRCA2. For all BRCA carriers, the penetrance of breast cancer to age 80 for those with no first-degree relative with breast cancer was 60.4% and 63.3% for those with at least 1 first-degree relative with breast cancer. The risk of breast cancer for BRCA carriers with no first-degree relative with breast cancer is substantial, and as a result, clinical management for these women should be the same as those for women with an affected relative.

Background: Breast reconstruction (BR) is an option for women who are treated with mastectomy; however, there has been concern regarding the oncologic safety of BR. In this study, we evaluated recurrences and mortality in women treated with mastectomy and compared outcomes in those treated with mastectomy alone to those with mastectomy plus transverse rectus adbominis (TRAM) flap BR. Methods: The prospective cohort study included women treated with mastectomy at Women’s College Hospital from 1987 to 1997. Women with TRAM flap BR were matched to controls based on age and year of diagnosis, stage, and nodal status. Patients were followed from the date of diagnosis until death or date of last follow-up. Hazard ratios were generated to compare cases and controls for outcome variables using Cox’s proportional hazards models. Results: Of 443 women with invasive breast cancer, 85 subjects had TRAM flap BR. Sixty-five of these women were matched to 115 controls. The mean follow-up was 11.2 (0.4–26.3) years. There were no significant differences between those with and without BR with weight, height, or smoking status. Women with TRAM flap were less likely to experience a distant recurrence compared to women without a TRAM flap (relative risk, 0.42; P = 0.0009) and were more likely to be alive (relative risk, 0.54; P = 0.03). Conclusions: Women who elect for TRAM flap BR after an invasive breast cancer diagnosis do have lower rates of recurrences and mortality than women treated with mastectomy alone. This cannot be explained by differences in various clinical or lifestyle factors.