Abstract Objective Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or BRCA2 mutation to reduce the risks of breast, ovarian and fallopian tube cancer. We measured the ...impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual functioning in women with a BRCA mutation. Methods Women who underwent prophylactic salpingo-oophorectomy between October 1, 2002 and June 26, 2008 for a known BRCA1 or BRCA2 mutation were invited to participate. Participants completed questionnaires before prophylactic surgery and again one year after surgery. Measures of sexual functioning and menopausal symptoms before and after surgery were compared. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy was evaluated. Results 114 women who underwent prophylactic surgery completed questionnaires before and one year after surgery. Subjects who were premenopausal at the time of surgery ( n = 75) experienced a significant worsening of vasomotor symptoms (hot flashes, night sweats and sweating) and a decline in sexual functioning (desire, pleasure, discomfort and habit). The increase in vasomotor symptoms and the decline in sexual functioning were mitigated by HRT, but symptoms did not return to pre-surgical levels. HRT decreased vaginal dryness and dyspareunia; however, the decrease in sexual pleasure was not alleviated by HRT. Satisfaction with the decision to undergo prophylactic salpingo-oophorectomy remained high regardless of increased vasomotor symptoms and decreased sexual function. Conclusions Women who undergo prophylactic salpingo-oophorectomy prior to menopause experience an increase in vasomotor symptoms and a decrease in sexual functioning. These symptoms are improved by HRT, but not to pre-surgical levels.
Abstract Objective In the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to ...determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. Methods All women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. Results Of 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p = 0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p = 0.032) while the time to genetic counseling decreased (p = 0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. Conclusions Despite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.
Abstract Objective As treatment based genetic testing becomes a reality, it is important to assess the attitudes and preferences of women newly diagnosed with ovarian cancer regarding genetic ...testing. The objective of this study was to determine when women with a diagnosis of high grade serous ovarian cancer would prefer to undergo genetic testing and factors that influence this preference. Methods Women over 18 years of age with a known diagnosis of high grade serous ovarian cancer diagnosed between October 2010–2013 were identified via the Princess Margaret Cancer Center Registry. Participants completed a questionnaire, which obtained preferences and attitudes towards genetic testing, cancer history, and demographic information. Results 120 of the 355 women identified (33.8%) completed the questionnaires. The median age at time of ovarian cancer diagnosis was 57 years (range 35–84). The majority of participants in this study were offered (94.6%) and pursued (84.8%) genetic testing. In this cohort, testing was most frequently offered at diagnosis (41.8%) or during treatment (19.1%). In this study, women with high grade serous ovarian cancer felt that genetic testing should be offered before or at the time of diagnosis (67.8%). Having a family history of breast or ovarian cancer was significantly (p = 0.012) associated with preferring genetic testing at an earlier time point in the disease course. Conclusions Our results demonstrate that women with high grade serous ovarian cancer acknowledge the personal and clinical utility of genetic testing and support test implementation at the time of cancer diagnosis.
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.
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.
Original Article Metcalfe, KA; Poll, A; O'Connor, A ...
Clinical genetics,
09/2007, Letnik:
72, Številka:
3
Journal Article
Recenzirano
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. PUBLICATION ABSTRACT
With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, ...the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the ∼13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5′ regulatory sequences.
B vitamins vitamins B-6, B-9 (folate), and B-12 play important roles in nucleotide biosynthesis and biological methylation reactions, aberrancies of which have all been implicated in carcinogenesis. ...In the general population, evidence has suggested that high circulating folate and folic acid (synthetic form of folate) supplement use may increase breast cancer risk, but the role of folate in BRCA-associated breast cancer is not clear.
We prospectively evaluated the relation between plasma folate, pyridoxal 5'-phosphate (PLP; the biologically active form of vitamin B-6), and vitamin B-12 and breast cancer risk in women with a BRCA1/2 mutation.
Baseline blood samples and biennial follow-up questionnaires were available for 164 BRCA1/2-mutation carriers with no previous history of cancer other than nonmelanoma skin cancer. Plasma folate, PLP, and vitamin B-12 concentrations were categorized dichotomously as high compared with low based on the upper 25% and the lower 75% of distribution, respectively. Cox proportional hazards were used to estimate the HR and 95% CI for the association between plasma biomarkers of each B vitamin and incident breast cancer.
Over a mean follow-up of 6.3 y, 20 incident primary invasive breast cancers were observed. Women with high plasma folate concentrations (>24.4 ng/mL) were associated with significantly increased breast cancer risk (HR: 3.20; 95% CI: 1.03, 9.92; P = 0.04, P-trend across quintiles = 0.07) compared with that of women with low plasma folate concentrations (≤24.4 ng/mL). Plasma PLP and vitamin B-12 concentrations were not associated with breast cancer risk.
Our data suggest that elevated plasma folate concentrations may be associated with increased risk of breast cancer in women with a BRCA1/2 mutation. Additional studies with a larger sample size and longer follow-up periods are warranted to clarify the relation between folate status and breast cancer risk in high-risk women.
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