Joan Murphy

The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation

OBJECTIVEnProphylactic 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.nnnMETHODSnWomen 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.nnnRESULTSn114 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.nnnCONCLUSIONSnWomen 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.

The impact of prophylactic salpingo‐oophorectomy on quality of life and psychological distress in women with a BRCA mutation

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.

Cervical Screening: A Guideline for Clinical Practice in Ontario

OBJECTIVEnTo develop guidelines to inform the Ontario Cervical Screening Programs invitations to women in the target population, provide evidence-based clinical practice guidance for practitioners, and inform policy decisions.nnnMETHODSnA systematic review was conducted of relevant websites, the Medline and EMBASE databases (2005 to November 2010), and the Cochrane Library (2005 to 2010). No guidelines or systematic reviews were located that addressed the topics of interest. The evidence base consisted of seven randomized controlled trials, three case-control studies, one cohort study, and one review article. A methodologist performed data identification and extraction. Review of the data and quality assessment was carried out by the authors, who have expertise in methodology, gynaecologic oncology, pathology, and family medicine. The systematic review methods and resulting recommendations were reviewed by an internal panel with clinical, methodological, and oncology expertise. External review was provided by Ontario clinicians and other experts.nnnCONCLUSIONSnThe guideline development process led to recommendations for the optimal primary cervical screening method, screening interval, and age of screening cessation for Ontario women in the target population. There was insufficient evidence to provide a recommendation for age of initiation of cervical screening with HPV testing. The creation of an organized screening program in the province will allow the implementation of evidence-based recommendations. We provide interim recommendations for cervical screening until HPV testing has been funded.

Uptake of clinical genetic testing for ovarian cancer in Ontario: A population-based study

BACKGROUNDnApproximately 13% of ovarian cancers in Canada are attributable to a mutation in BRCA1 or BRCA2. In 2001, genetic testing for BRCA1 and BRCA2 became freely available to all women in Ontario with a diagnosis of invasive ovarian cancer. It is unknown what proportion of women with ovarian cancer receive genetic testing as a result of this recommendation.nnnMETHODSnPatients in Ontario who had been diagnosed with epithelial ovarian cancer from 2002 to 2004 were identified using the Ontario Cancer Registry. Information was collected on demographic and risk factors, including information on previous testing for BRCA1 and BRCA2. Women were asked to provide a blood sample for genetic testing or to provide a genetic test result if clinical testing had been done. Genetic testing for BRCA1 and BRCA2 mutations was conducted on all blood samples.nnnRESULTSnOf the 416 women, 80 women (19%) had undergone previous clinical genetic testing for BRCA1 and BRCA2. Of these 80 women, 30% had a positive genetic test result, compared to 5% of 336 women who had not had clinical genetic testing (p<0.0001). Sixty percent of all mutations were identified within this group of 80 women.nnnCONCLUSIONSnGenetic testing is available in Ontario to all women with invasive ovarian cancer. However, only a small proportion of women are being referred for testing. This study suggests that increased public awareness directed at physicians and at women with cancer may expand the use of genetic testing.

HPV Testing in Primary Cervical Screening: A Systematic Review and Meta-Analysis

OBJECTIVEnPrevious findings from cross-sectional studies have shown human papillomavirus (HPV) testing to be more sensitive than cytology testing for primary cervical screening. This systematic review aims to assess whether the increase in baseline detection with HPV testing corresponds to lower rates in subsequent screening rounds.nnnMETHODSnWe searched Medline, EMBASE, and the Cochrane Library for randomized controlled trials (published from 2005 to 2010) comparing HPV-based and cytology-based cervical screening. Primary outcomes of interest were relative rates of higher grade cervical intraepithelial neoplasia and invasive cervical cancer. Secondary outcomes included test performance characteristics and colposcopy referral rates. Results were pooled where possible using a random effects model.nnnRESULTSnSeven randomized trials were identified. Across studies, HPV testing was more accurate than conventional cytology and detected significantly more CIN3+ in the first screening round (Mantel-Haenszel [M-H] risk ratio 1.67; 95% CI 1.27 to 2.19) and significantly less in the second screening round (M-H RR 0.49; 95% CI 0.37 to 0.66). There were no differences in pooled rates of CIN2+ (M-H RR 1.19; 95% CI 0.94 to 1.50) and CIN3+ (M-H RR 1.09; 95% CI 0.84 to 1.42), but there was a higher pooled rate of CIN2 (M-H RR 1.37; 95% CI 1.12 to 1.68) over two screening rounds. A trend towards lower rates of invasive cervical cancer was observed.nnnCONCLUSIONnOrganized screening programs in higher resource settings should consider adopting HPV testing as the primary screening test for women 30 or 35 years of age and older. Further research is needed to determine optimal screening strategies for younger women.

Psychological side-effects of clomiphene citrate and human menopausal gonadotrophin

Objective.u2003This study evaluated the psychological side-effects of clomiphene citrate (CC) and hMG in women undergoing fertility treatment. Method.u2003This study was a cross-sectional, self-report survey of 454 women at various stages of treatment for infertility. At the time of study, 139 women had not taken fertility drugs and 315 women had taken one or more cycles of CC or hMG. All subjects were asked to complete the State-Trait Anxiety Inventory (STAI). Women taking CC or hMG were also asked to complete a self-administered questionnaire on the side-effects of their medications. Result(s).u2003In the CC group (nu200a=u200a162) and hMG group (nu200a=u200a153), 77.8% (126 of 162) and 94.8% (145 of 153) reported at least one side-effect, respectively. Irritability, mood swings, feeling down, and bloating had high frequencies in both CC and hMG groups, with a higher mean number of side effects reported in the hMG group (4.4u200a±u200a3.7 for the CC group and 6.8u200a±u200a3.7 for the hMG group, pu200a<u200a0.001). There was no significant difference among the CC, hMG and no medication groups for mean state and trait anxiety scores. However, there were significant differences among the three side-effect groups (those who reported 1 to 4, 5 to 7, and more than 7 side-effects) for the mean scores of state (dfu200a=u200a2, Fu200a=u200a8.7, pu200a<u200a0.001) and trait (dfu200a=u200a2, Fu200a=u200a11.9, pu200a<u200a0.001) anxiety in women taking fertility drugs. Conclusion(s).u2003Women taking CC or hMG reported high frequencies of psychological side-effects, and should be advised of these before treatment.

Issues surrounding lymphadenectomy in the management of endometrial cancer

The development of surgical staging in the management of endometrial cancer has arisen over the last several decades with anticipated benefits including prognostic information, tailoring of adjuvant treatment, and a possible therapeutic effect. This review addresses the important issues surrounding lymphadenectomy in endometrial cancer. Other issues including the use of sentinel lymph node techniques, advanced imaging modalities and the consideration of a binary grading system to simplify triaging of patients will also be discussed. J. Surg. Oncol. 2009;99:232–241.

ROLE OF ADJUVANT RADIOTHERAPY IN GRANULOSA CELL TUMORS OF THE OVARY

PURPOSEnTo review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary.nnnMETHODS AND MATERIALSnThe records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint.nnnRESULTSnA total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up.nnnCONCLUSIONnOvarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

Breast and ovarian cancer risk perception after prophylactic salpingo-oophorectomy due to an inherited mutation in the BRCA1 or BRCA2 gene.

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.