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.

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.

Impact of rapid genetic testing for BRCA1 and BRCA2 at time of breast cancer diagnosis on psychosocial functioning.

PURPOSE: Many women are being offered rapid genetic testing (RGT) for cancer predisposition genes, at the time of breast cancer diagnosis prior to surgery. The goal of this study was to determine if psychosocial functioning was affected in women receiving RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis. METHODS: Participants were women with invasive breast cancer diagnosed between 2013 and 2018, at four centres in Toronto, Canada. Eligible women were referred into the study by their surgeon at the time of diagnosis. Participants received pre-test genetic counselling and were offered RGT for BRCA1 and BRCA2. Standardized questionnaires (Impact of Event Scale and Hospital Anxiety and Depression Scale) were completed before genetic counselling, and follow-up questionnaires at one-week and one-year post-genetic test result disclosure (higher scores indicate higher symptoms). RESULTS: 1007 women had RGT; 60 women (6.0%) were found to have a BRCA1 or BRCA2 mutation, 80 women (7.9%) had a VUS, and 867 (86.1%) had a negative test result. At one-week post-testing, there were no differences in distress (p = 0.32), anxiety (p = 0.14), or depression (p = 0.42) between women with a BRCA1/2 mutation and those with a negative result. At one year, there were no differences in distress (p = 0.75) or anxiety (p = 0.13) between women with a BRCA1 or BRCA/2 mutation and those with a negative result. However, women with a BRCA1 or BRCA2 mutation had significantly lower depression scores compared to women with a negative result (p = 0.03). CONCLUSION: For women who have RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis, identifying a BRCA1 or BRCA2 mutation does not impair psychosocial functioning in the short or long term.

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.

The relationship between the predicted risk of death and psychosocial functioning among women with early-stage breast cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Longitudinal Study of Psychosocial Outcomes Following Surgery in Women with Unilateral Nonhereditary Breast Cancer.

INTRODUCTION: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: Psychosocial outcomes are not improved with contralateral prophylactic mastectomy in women with unilateral breast cancer. Our data may inform women considering contralateral prophylactic mastectomy.

Frequency of Contralateral Prophylactic Mastectomy in Breast Cancer Patients with a Negative BRCA1 and BRCA2 Rapid Genetic Test Result.

BACKGROUND: There is an increasing desire for contralateral prophylactic mastectomy (CPM) among patients with unilateral breast cancer. It is unknown if risk assessment and genetic testing at the time of diagnosis will aid women in their surgical choice. We report on the uptake and predictors of CPM in women receiving a negative genetic test result for BRCA1 and BRCA2 mutations before surgery. METHODS: Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four academic health sciences centers in Toronto, Canada. Genetic counseling (risk assessment) and genetic testing was performed prior to surgery. Women were asked about their surgical preference before surgery. At 1 year post-surgery we asked what surgery was completed. This study reports on women who received a negative BRCA1/BRCA2 result. RESULTS: A total of 766 women with a mean age of 46 years (range 21-82) were included in the analysis. Before genetic counseling and testing, 37% of the women were undecided or leaning towards CPM; however, after receiving a negative BRCA test, 15% of the women opted for CPM. Thirty percent of women whose mother died of breast cancer elected for CPM, compared with 15% of women whose mother did not die of breast cancer (p = 0.03). CONCLUSIONS: Women receiving a risk assessment and negative BRCA1/BRCA2 genetic test result before surgery use this information to guide their surgical decision. Uptake of CPM for women who were planning on CPM before genetic testing decreases after receiving a negative BRCA1/BRCA2 genetic test result.

Rapid Genetic Testing for BRCA1 and BRCA2 Mutations at the Time of Breast Cancer Diagnosis: An Observational Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001). Of the BRCA-positive patients, 95.7% reported that they used their genetic test result to make a surgical decision. CONCLUSIONS: The women provided with RGT at the time of breast cancer diagnosis use the genetic information to make treatment decisions, and the majority of those identified with a BRCA mutation elect for a bilateral mastectomy.

Late cognitive outcomes among allogeneic stem cell transplant survivors: follow-up data from a 6-year longitudinal study.

CONTEXT: Survivors of allogeneic hematopoietic stem cell transplantation (alloHCT) may experience cognitive impairment over time post-treatment, but early identification of these individuals is limited. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Preconsultation Educational Group Intervention Can Address the Knowledge Gap in Postmastectomy Breast Reconstruction.

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.

Predictors of long-term cancer-related distress among female BRCA1 and BRCA2 mutation carriers without a cancer diagnosis: an international analysis.

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.

Year 1: Experiences of a tertiary cancer centre following implementation of reflex BRCA1 and BRCA2 tumor testing for all high-grade serous ovarian cancers in a universal healthcare system.

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.

Preferences for breast cancer prevention among women with a BRCA1 or BRCA2 mutation.

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.

Predictors of uptake of contralateral prophylactic mastectomy in women with nonhereditary breast cancer.

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 < .0001). The rate of CPM was significantly higher in women with noninvasive breast cancer compared with those with invasive breast cancer (P < .0001). Women who elected to undergo CPM had lower levels of presurgical breast satisfaction (P = .01) and optimism (P = .05) compared with women who did not undergo CPM. CONCLUSIONS: Psychosocial functioning at the time of breast cancer surgery decision making impacts decisions related to CPM. Women who have lower levels of breast satisfaction (body image) and optimism are more likely to elect to undergo CPM. It is important for health care providers to take psychosocial functioning into consideration when discussing surgical options.

Psychosocial Functioning in Women with Early Breast Cancer Treated with Breast Surgery With or Without Immediate Breast Reconstruction.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Predictors of mammographic density among women with a strong family history of breast cancer.

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.

Uptake of Preimplantation Genetic Diagnosis in Female BRCA1 and BRCA2 Mutation Carriers.

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 < 0.04). Experiencing previous infertility was the only significant predictor of uptake of IVF/PGD (p < 0.001), which may suggest that BRCA status is secondary to infertility in the decision-making process for PGD in women with a BRCA mutation.

Preferences for breast cancer risk reduction among BRCA1/BRCA2 mutation carriers: a discrete-choice experiment.

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.

Effect of decision aid for breast cancer prevention on decisional conflict in women with a BRCA1 or BRCA2 mutation: a multisite, randomized, controlled trial.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.