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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

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.

Introduction For women who have mastectomy, breast reconstruction is an option which may improve psychosocial functioning. The purpose of this study was to evaluate changes in psychosocial functioning over a long follow-up period after mastectomy, specifically examining the differences between those with mastectomy alone and those who underwent postmastectomy delayed breast reconstruction (DBR). Methods This was a prospective longitudinal survey study of women with mastectomy in which a repeated measures design was used to compare psychosocial function scores over 3 timepoints: 1) pre-mastectomy; 2) one year post-mastectomy; and 3) long-term post-mastectomy (mean 6.3 years). In addition, psychosocial functioning was compared between the mastectomy alone group and the group who elected for DBR. Results 67 women who completed questionnaires at all three time points were included. The long-term follow-up time post-mastectomy was 75.2 months (6.3 years). Twenty-eight women (41.8%) underwent DBR in the study period. For the entire cohort, between one-year and long-term post-mastectomy, there were significant improvements in scores for body concerns (P = 0.03), cancer-related distress (P = 0.01), and total distress (P = 0.04). At long-term follow-up, women with DBR had significantly higher levels of total distress (P = 0.01), obsessiveness (P = 0.03), and cancer-related distress (P = 0.02) compared to those with mastectomy alone. There were no differences in quality of life between the two groups at any time point. Conclusions Psychosocial functioning improves over time in patients treated with mastectomy in the long-term breast cancer survivorship period, which may be related to the effect of time post-treatment, rather than an effect of choice for or against DBR. J. Surg. Oncol. 2015 111:258–264. © 2014 Wiley Periodicals, Inc.

Background & Objectives It is not known if optimism influences regret following major reconstructive breast surgery. We examined the relationship between dispositional optimism, major complications and decision regret in patients undergoing microsurgical breast reconstruction. Methods A consecutive series of 290 patients were surveyed. Independent variables were: (1) dispositional optimism and (2) major complications. The primary outcome was Decision Regret. A multivariate regression analysis determined the relationship between the independent variables, confounders and decision regret. Results Of the 181 respondents, 63% reported no regret after breast reconstruction, 26% had mild regret, and 11% moderate to severe regret. Major complications did not have a significant effect on decision regret, and the impact of dispositional optimism was not significant in Caucasian women. There was a significant effect in non-Caucasian women with less optimism who had significantly higher levels of mild regret 1.36 (CI 1.02–1.97) and moderate to severe regret 1.64 (CI 1.0–93.87). Conclusions This is the first paper to identify a subgroup of non-Caucasian patients with low dispositional optimism who may be at risk for developing regret after microsurgical breast reconstruction. Possible strategies to ameliorate regret may involve addressing cultural and language barriers, setting realistic expectations, and providing more supports during the pre-operative decision-making phase. J. Surg. Oncol. 2013; 108:526–530. © 2013 Wiley Periodicals, Inc.

There is a significant variation in the uptake of cancer risk reducing options by women with a BRCA1 or BRCA2 mutation. It is currently unclear why these differences exist and it is possible that recommendations vary between providers and these influence patient decisions. Eligible health care providers who provide genetic counseling for hereditary breast and ovarian cancer families in Canada were identified. Each provider was asked to complete a study specific questionnaire that included their opinion of various cancer risk reduction options and their recommendations for specific cases. Respondents recommended prophylactic oophorectomy more often than prophylactic mastectomy or tamoxifen for women with a BRCA1 or BRCA2 mutation (p

BRCA testing services are now offered by various healthcare providers, thus it is important to evaluate whether the implementation of cancer risk management (CRM) strategies varies by service provider. Using a registry-based sample of 795 female BRCA mutation carriers, we explored the association between uptake of CRM strategies with duration of genetic counseling (GC) sessions, provider type, and other demographic and clinical variables. All participants completed a baseline questionnaire. Information about uptake of CRM strategies was collected for a subset of 438 participants who completed additional questions. Summary statistics and Pearson chi-squared analysis were used to examine the associations between demographic and clinical variables with service delivery factors and with the uptake of various CRM strategies. Overall uptake of CRM strategies was high across all provider types. However, GC sessions were longer when provided by a genetics professional than by another provider (p

BACKGROUND: A family history of breast cancer has been shown to affect psychosocial functioning. However, the majority of research has focused on the daughters of patients with breast cancer and families with multiple relatives with the disease. The purpose of the current study was to examine cancer-related distress and breast cancer risk perception, and further examine the predictors of these outcomes, in the sisters of newly diagnosed patients with breast cancer without a previous family history of the disease. METHODS: Sisters of newly diagnosed index breast cancer patients were identified and asked to complete a study-specific questionnaire (demographics and cancer risk perception) and the Impact of Events Scale. Pathological information was abstracted from the medical chart for the index breast cancer patients. RESULTS: A total of 205 sisters completed the questionnaires. The mean time between breast cancer diagnosis and the sisters' completion of the questionnaire was 9.8 months. Approximately one-half of the women scored in the moderate or severe distress range. The most significant predictor of cancer-related distress was perceived lifetime breast cancer risk (P = .04). Women with a lifetime risk of breast cancer > 20% were more than twice as likely to have moderate or severe distress compared with those with a lifetime risk of < 20%. CONCLUSIONS: Cancer-related distress is high in the sisters of newly diagnosed patients with breast cancer in whom there is no other family history of breast cancer. Specifically, women with a perceived lifetime risk of breast cancer of > 20% experienced the highest levels of distress. Future interventions that target this group should be considered. Cancer 2013. © 2013 American Cancer Society.

OBJECTIVES The objective of this study was to measure the impact of prophylactic salpingo-oophorectomy on health-related quality of life and psychological distress in women. METHODS Women who underwent prophylactic salpingo-oophorectomy between August 20, 2003 and June 26, 2008 because of a BRCA1 or BRCA2 mutation were invited to participate. Participants completed three questionnaires (SF-12(®) Health Survey, Brief Symptom Inventory and the Impact of Events Scale) before prophylactic surgery and again 1 year after surgery. Measures of health-related quality of life, of general psychological distress and of ovarian cancer worry before and after surgery were compared. RESULTS Few women who underwent salpingo-oophorectomy experienced a worsening in physical or mental health functioning after salpingo-oophorectomy. On average, women experienced less ovarian cancer-specific worry after surgery; 34.3% experienced moderate to severe ovarian cancer-specific distress before surgery, compared with 18.6% after surgery. CONCLUSIONS For most women, physical and mental health-related quality of life did not deteriorate after prophylactic salpingo-oophorectomy, and they were less worried about ovarian cancer. A subset of women continued to experience moderate to severe cancer-specific distress. Identification of these women is important in order to provide continued counseling and support.

BRCA+ breast cancer patients face high risk for a second breast cancer and ovarian cancer. Helping these women decide among risk-reducing options requires effectively conveying complex, emotionally-laden, information. To support their decision-making needs, we developed a web-based decision aid (DA) as an adjunct to genetic counseling. Phase 1 used focus groups to determine decision-making needs. These findings and the Ottawa Decision Support Framework guided the DA development. Phase 2 involved nine focus groups of four stakeholder types (BRCA+ breast cancer patients, breast cancer advocates, and genetics and oncology professionals) to evaluate the DA’s decision-making utility, information content, visual display, and implementation. Overall, feedback was very favorable about the DA, especially a values and preferences ranking-exercise and an output page displaying personalized responses. Stakeholders were divided as to whether the DA should be offered at-home versus only in a clinical setting. This well-received DA will be further tested to determine accessibility and effectiveness.

It is not known to what extent participation in a genetic testing program for BRCA1 and BRCA2, which does not include an extensive pre-test counselling session, influences cancer-related distress, cancer risk perception and patient satisfaction. Unselected Jewish women in Ontario were offered genetic testing for three common Jewish BRCA mutations. Before testing and 1-year post-testing, the women completed questionnaires which assessed cancer-related distress, cancer risk perception, and satisfaction. A total of 2080 women enrolled in the study; of these, 1516 (73%) completed a 1-year follow-up questionnaire. In women with a BRCA mutation, the mean breast cancer risk perception increased from 41.1% to 59.6% after receiving a positive genetic test result (p = 0.002). Among non-carriers, breast cancer risk perception decreased slightly, from 35.8% to 33.5% (p = 0.08). The mean level of cancer-related distress increased significantly for women with a BRCA mutation, but did not change in women without a mutation; 92.8% expressed satisfaction with the testing process. The results of this study suggest that the majority of Jewish women who took part in population genetic screening for BRCA1 and BRCA2 were satisfied with the delivery of genetic testing and would recommend testing to other Jewish women. However, women with a BRCA mutation experienced increased levels of cancer-related distress.

It is often recommended that women who carry a mutation in the BRCA1 or BRCA2 gene have their ovaries and fallopian tubes removed to reduce their risk of gynecologic cancer. The aim of this study was to evaluate women's perception of their risk of breast and ovarian cancer before and after prophylactic salpingo-oophorectomy. We surveyed 127 women who carry a BRCA1 or BRCA2 mutation and who underwent prophylactic salpingo-oophorectomy at the University Health Network, Toronto. Subjects were asked to estimate their risks of breast and ovarian cancer before and after surgery. Their perceived risks of cancers were then compared with published risks, based on their mutation status. BRCA1 carriers estimated their risk of breast cancer risk to be, on average, 69% before surgery and 41% after surgery. They estimated their risk of ovarian cancer to be 55% before surgery and 11% after surgery. BRCA2 carriers estimated their risk of breast cancer to be 69% prior to surgery and 45% after surgery and their perceived risk of ovarian cancer to be 43% before surgery and 8% after surgery. Compared with published risk figures, the perceived risk of ovarian cancer before prophylactic salpingo-oophorectomy was overestimated by 47% of BRCA1 mutation carriers and by 61% of BRCA2 mutation carriers. Most women who have undergone genetic counseling and subsequently choose prophylactic salpingo-oophorectomy accurately perceive their risk of breast cancer. However, in this study, many women overestimated their risk of ovarian cancer, particularly women who carry a BRCA2 mutation.

Several cancer genetics centres offer testing for specific BRCA1 and BRCA2 mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA1 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198-200; Roa et al., Nat Genet 1996: 14: 185-187; Oddoux et al., Nat Genet 1996: 14: 188-190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCA1 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA1 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCA2 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast-ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.

For women who carry a mutation in BRCA1 or BRCA2, the risk of breast cancer is up to 87% by the age of 70. There are options available to reduce the risk of breast cancer; however, each option has both risks and benefits, which makes decision making difficult. The objective is to develop and pilot test a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. The decision aid was developed and evaluated in three stages. In the first stage, the decision aid was developed and reviewed by cancer genetics experts. The second stage was a review of the decision aid by women with a BRCA1 or BRCA2 mutation for acceptability and feasibility. The final stage was a pre-test--post-test evaluation of the decision aid. Twenty-one women completed the pre-test questionnaire and 20 completed the post-test questionnaire. After using the decision aid, there was a significant decline in mean decisional conflict scores (p = 0.001), a significant improvement in knowledge scores (p = 0.004), and fewer women uncertain about prophylactic mastectomy (p = 0.003) and prophylactic oophorectomy (p = 0.009). Use of the decision aid decreased decisional conflict to levels suggestive of implementation of a decision. In addition, knowledge levels increased and choice predisposition changed with fewer women being uncertain about each option. This has significant clinical implications as it implies that with greater uptake of cancer prevention options by women with a BRCA1 or BRCA2 mutation, fewer women will develop and/or die of hereditary breast cancer.

BACKGROUND A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas. METHODS The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size. RESULTS A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20). CONCLUSIONS The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma. Cancer 2003. ©2003 American Cancer Society. DOI 10.1002/cncr.11688

The purpose of this study was to determine the current psychosocial functioning of women who had previously had a bilateral prophylactic mastectomy. Women in the province of Ontario who had undergone prophylactic mastectomy between 1991 and 2000 were asked to complete questionnaires that assessed psychological distress, sexual activity, overall satisfaction with decision to have a prophylactic mastectomy, and body image. Ninety-seven percent of the women were satisfied with their decision to have a prophylactic mastectomy, but young women (

Metcalfe KA, Liede A, Trinkaus M, Hanna D, Narod SA. Evaluation of the needs of spouses of female carriers of mutations in BRCA1 and BRCA2. Clin Genet 2002: 62: 464–469. © Blackwell Munksgaard, 2002 The process of genetic testing involves the entire family, including spouses. The objective of this study was to measure the specific needs and to describe the experiences of spouses of women who received genetic counseling for a positive BRCA1/2 result. We surveyed 59 spouses of female mutation carriers. The mean length of relationships was 26 years (range: 2.5–50 years). All were supportive of their spouses' decision to undergo genetic testing and counselling. Four respondents stated that they wished that they had received additional support at the time of test disclosure and 20% felt that their wives had received inadequate support. One-quarter of the spouses believed that their relationship had changed because of genetic testing; most felt that they had become closer to their wives. Husbands were most concerned about the risk of their wife dying of cancer (43%), followed by the risk of their spouse developing cancer (19%) and the risk that their children would test positive for the BRCA mutation (14%). Distress levels, measured by the Impact of Event scale, suggest that few spouses were experiencing clinical levels of distress.

BACKGROUND Many women who are at an elevated risk of developing breast carcinoma choose prophylactic mastectomy to decrease their risk. We conducted a population-based study to review the indications for, and patterns of practice of prophylactic mastectomy in Ontario, Canada, since 1991. METHODS A medical chart review was conducted at 33 hospitals that were identified as having conducted at least one prophylactic mastectomy. All bilateral mastectomy patients with no diagnosis of invasive or in situ breast carcinoma were eligible. RESULTS The number of prophylactic bilateral mastectomies performed varied from 6 to 19. The mean age of women undergoing prophylactic mastectomy was 43.5 years. Eighty percent of the women had prophylactic mastectomy performed because of a family history of breast carcinoma (89 of 99) or because of a known BRCA1 or BRCA2 mutation (10 of 99). Twenty percent of the women had no family history, but had the surgery for other benign breast conditions. Women with a family history of breast carcinoma were much more likely to have a total mastectomy (89%) than a subcutaneous mastectomy (11%). Sixty percent of the women had reconstructive surgery following mastectomy. CONCLUSIONS Prophylactic mastectomy is not performed on a large scale. The introduction of genetic testing for BRCA1 and BRCA2 has the potential to change the patterns of practice for prophylactic mastectomy. Cancer 2002;95:236–42. © 2002 American Cancer Society. DOI 10.1002/cncr.10680

Erratum to: J Genet CounselDOI 10.1007/s10897-011-9350-4A typographical error was printed in the acknowledgementof a City of Hope grant in Culver JO, MacDonald DJ,Thornton AA, Sand SR, Grant M, Bowen DJ, Burke H,Garcia N, Metcalfe KA, Weitzel JN. Development andevaluation of a decision aid for BRCA carriers with breastcancer. J Genet Couns. 2011 Jun; 20(3):294–307.doi: 10.1007/s10897-011-9350-4. PMID: 21369831.The grant number referenced is “P20 CA 33572.” Thecorrect number is “P30CA033572.”

The purpose of the study was to develop, standardize and test a model of supportive-expressive group therapy for women with BRCA1/2 mutations. Method: A pre/post design was used. Results: 38/70 participants (54.3%) had a previous diagnosis of cancer and 32 (45.7%) had no cancer. There were statistically significant reductions in the levels of intrusion or cancer worries (t [64] = 2.9, p = 0.004), depression (t [69] = 2.5, p = 0.015), anxiety (t [68] = 2.2, p = 0.033) and global psychosocial functioning (t [60] = 2.75, p = 0.008). A significant number of women made decisions concerning prophylactic surgery (oophorectomy/mastectomy). Conclusions: These findings are encouraging and suggest the effectiveness of a group intervention for both affected and unaffected carriers and have implications for a future randomized trial.