Risk For Hereditary Ovarian Cancer Research Articles

My individualized risk reduction for ovarian cancer (MIRROR): Development of a patient decision aid for risk-reducing surgery in hereditary risk for ovarian cancer (158)

My individualized risk reduction for ovarian cancer (MIRROR): Development of a patient decision aid for risk-reducing surgery in hereditary risk for ovarian cancer (158)

Abstract P6-02-08: Identifying preferences that may motivate choice of ovarian cancer risk prevention strategies using a discrete choice experiment

Abstract Background: Women with a familial or hereditary risk for ovarian cancer are at a much greater risk of developing ovarian cancer compared with women in the general population. This high risk demands prevention strategies to reduce ovarian cancer incidence and mortality. Currently there is little information about how women with a hereditary risk for ovarian cancer make trade-offs when choosing among prevention strategies and their associated risks. In anticipation of the likelihood that when given more personalized risk estimates, patients may have different preferences based on their mutation specific cancer risk as well as demographic and clinical factors, it is critical that we have the necessary information to develop counseling models that are tailored to individual patients’ preferences for cancer risk reduction and tolerance of associated risks. Methods: We performed a discrete choice experiment to investigate how women at higher risk of ovarian cancer weigh benefits (e.g. reduced risk of ovarian) versus costs (e.g. increased risk of heart disease) in choosing a treatment strategy. N=396 pre-menopausal women with a personal history of breast cancer or familial history suggestive of increased breast and/or ovarian cancer risk were surveyed from August, 2019, to January, 2022. Participants were asked to choose between two sets of attributes that specified type of surgery (risk-reducing salpingo-oophorectomy [RRSO], risk reducing salpingectomy [RRS] vs. non-surgical surveillance), age of menopause (natural versus immediate), quality of menopausal symptoms (mild, moderate, severe), and risk of ovarian cancer, heart disease, or osteoporosis. Risks of disease varied in discrete intervals. We fit a Bradley-Terry logistic regression to estimate preferences. The binary response was the randomly generated choice set selected versus the set not selected. Results: Women were more likely to choose sets with either surveillance (odds ratio [OR]= 1.28, 95% confidence interval [CI] 0.98, 1.67) or RRSO (OR= 1.39, 95% CI 1.07, 1.81) over RSS. In weighing trade-offs in the choice sets that included type of surgery, women had a stronger independent preference for reducing the risk of ovarian cancer (OR= 0.66 of choosing set per 10% increase in risk, 95% CI 0.62, 0.71) than in reducing the risk of osteoporosis (OR= 0.82 per 10% increase, 95% CI 0.75, 0.90) or heart disease (OR = 0.82 per 10% increase, 95% CI 0.76,0.88). Women also had a strong preference for delaying the expected age of ovarian cancer (OR= 1.34 per 10-year increase in age, 95% CI 1.19, 1.51). Women had strong preferences for having a natural age of menopause (OR= 1.58 compared to immediate menopause post-treatment, 95% CI 1.27, 1.95), and better less severe symptoms (OR= 0.65 for each ordinal increase in the severity of symptoms, 95% CI 0.60, 0.70). Conclusions: Our results suggest that women may prefer either surveillance or the most extensive type of surgery (RRSO) over more limited surgery (RRS). In weighing trade-offs, reducing the risk of ovarian cancer seemed to be more important than reducing the risk of osteoporosis or heart disease. Still, having a natural age of menopause and reducing the severity of symptoms could motivate the choice of treatment. Our work will allow us to estimate thresholds of measured factors that may motivate women to choose a specific treatment strategy. Citation Format: Mary Daly, Brian Egleston, Kaitlyn Lew, Lisa Bealin, Alexander Husband, Jill Stopfe, Pawel Przybysz, Olga Tchuvatkina, Yu-Ning Wong, Judy Garber, Timothy Rebbeck. Identifying preferences that may motivate choice of ovarian cancer risk prevention strategies using a discrete choice experiment. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-08.

Systematic mapping review of guidelines for BRCA1/2 genetic testing globally: investigating geographic and regional disparities in health equity for women and families at risk for hereditary ovarian cancer

ObjectiveIdentification of persons at risk for hereditary syndromes through genetic testing prior to cancer diagnosis may proactively reduce the cancer burden morbidity and mortality. Using a framework of health equity,...

Hereditary ovarian cancer risk reduction: a retrospective evaluation of patient perspectives and service provision at a regional hereditary gynaecologic cancer clinic 2006–2016

BackgroundGermline pathogenic variants in BRCA1/2 have been established in hereditary breast and ovarian cancer (HBOC) syndrome and result in significantly elevated lifetime risk of ovarian cancer. Risk reduction interventions are presently the only effective means of improving survival and specialized counselling clinics have been established as an effective means of aiding this population in navigating complex decisions surrounding these interventions. This study sought to evaluate patient perceptions of a specialized counselling clinic for patients with HBOC Syndrome and referral patterns to this clinic.MethodsWe completed a retrospective review of 200 patients with HBOC in Nova Scotia, Canada seen through Maritime Medical Genetics Services between 2006 and 2016. Data were collected on referral pattern to the Hereditary Gynaecologic Risk Reduction Clinic (HGRRC), demographics, health history, and uptake of risk-reducing interventions. Participants were invited to complete a questionnaire about their experience.Results156/200(78%) women were referred to HGRCC and 135/156 (85.9%) of those referred attended their appointment. 124/200 (62%) were over age 40 at the time of testing. The mean time from referral to HGRCC appointment was 134.68 days (SD 85.78). 85/135 (63%) underwent risk-reducing bilateral salpingo-oophorectomy following their HGRCC appointment. The questionnaire was completed by 94/188 (50.3%) women. Most participants found information received from genetics clinics (81/94; 91%) and genetic counsellors (87/94; 95%) most helpful in making choices around risk-reduction strategies. 83/94 (88%) participants felt they had sufficient information to make an informed decision.ConclusionThe majority of women with HBOC in Nova Scotia during the study period were referred to and counselled through HGRRC. Genetic counselling was found most valuable in risk-reduction decision making, which highlights the importance of a multidisciplinary team. Patients viewed this clinic as an effective care model to support informed choice about risk-reducing intervention.

Methylated DNA markers discriminate ovarian cancer from benign tissue in BRCA carriers.

e17610 Background: Methylated DNA markers (MDMs) associated with sporadic ovarian cancer (OC) are detected in plasma from patients with treatment naïve tumors, but not cancer-free controls. To assess potential benefits to patients at risk for hereditary OC, the aim of this study was to measure the performance of validated sporadic OC MDMs in OC and benign ovarian tissue (BOT), surgically obtained from germline BRCA1 or BRCA2 ( BRCA1/2) mutation carriers. Methods: BRCA1/2 carriers with OC and BRCA1/2 carriers who had undergone risk-reducing salpingo-oophorectomy (SO) were identified at a comprehensive cancer center. BRCA1/2 carriers in both OC and BOT groups were balanced on age and year of surgery with non- BRCA carriers with sporadic OC or benign indications for SO. OC and BOT formalin fixed paraffin embedded (FFPE) tissues were macrodissected following pathologist selection of representative sites; DNA was extracted, and bisulfite converted. 15 OC MDMs ( GDF6, IFFO1, MAX.chr1.147790358, MAX.chr6.10382190, MAX.chr11.14926602, C2CD4D, PDRM14, NCOR2, SKI, DSCR6, SIM2, PALLD, CDO1, GPRIN1, BCAT1) previously identified in sporadic OC were assayed by quantitative methylation specific PCR, normalized by β-actin, by blinded personnel. Areas under the receiver operating characteristic curve (AUC) were generated for each MDM to assess discrimination of OC from benign tissue and compared between BRCA1/2 and sporadic (non- BRCA) patients, using a z-test. Results: Among BRCA1/2 carriers, there were 48 OC ( BRCA-OC) and 48 BOT ( BRCA-BOT); among non- BRCA, we matched 48 OC (Sporadic-OC) and 48 BOT (non- BRCA-BOT). The median AUC for OC MDM discriminated between OC and BOT with AUCs in BRCA1/2 carriers was 0.87, (IQR, 0.83-0.93). Sporadic-OC vs non- BRCA-BOT median AUC was 0.88 (IQR, 0.83-0.92). AUCs were not significantly different for each MDM when stratified by BRCA or sporadic status. MDMs with an AUC of ≥0.9 in either group are shown (Table). Conclusions: OC MDMs identified and validated in sporadic OC are highly discriminant for OC from BOT in DNA extracted from tissues of people who carry a BRCA1/2 mutation. Testing the performance of these OC MDMs in plasma from BRCA1/2 carriers with and without OC may be of clinical value for high-risk patients and inform multi-cancer early detection testing strategies.[Table: see text]

Organizational forms and methods of early diagnosis of hereditary tumors

Background: With the development of genetic research in oncology, it has become possible to track and identify early and preclinical forms of hereditary oncological diseases, which allows timely and effective preventive and therapeutic measures in relation to relatives at risk. Aim of the study: Assessment of genetically determined neoplasms in the region and the development of organizational forms and methods for early diagnosis. Material and methods: 10,727 residents of the Belarus-Poland border region were examined. Clinical and medical history data of 2,054 patients with tumors of the breast (1406), ovaries (239), and colon (409) were analyzed. As a result of the questionnaire, three main observation groups were formed: “high risk of hereditary cancer”, “hereditary cancer suspected”, and “no risk of hereditary cancer”. Results: Register and hospital screenings were the most informative types of screening. Of the 149 HBC patients who underwent molecular genetic testing, BRCA1 gene mutations were found in 5.37%, 5382insC in all cases. Seven mutations were detected in 77 individuals with a diagnosis of HOC and in 6 cases 5382insC and in 2 - 4145delA. Signs of hereditary ovarian cancer and suspicion of it were found in 1.12%, including people who were found to have a high risk of hereditary ovarian cancer. By their effectiveness, register and hospital screenings significantly exceeded the population, p<0.01. 1.67% of women suffering from this disease met the high clinical risk criteria for hereditary ovarian cancer. A high clinical risk of hereditary tumor genesis was established in 0.73% of cases among patients with a diagnosis of colon cancer. Conclusions: The results of assessing the clinical risk of hereditary cancer according to population screening indicates that approximately 1.2% of the population has an increased clinical risk of developing hereditary breast, ovarian, and colon cancer.

Contraception options for patients with known hereditary risk for ovarian cancer.

For patients with a known hereditary risk of ovarian cancer, primary prevention typically is accomplished through prophylactic bilateral salpingo-oophorectomy. However, some patients may wish to preserve fertility or delay menopause and its associated comorbidities. This article discusses appropriate methods of contraception for these patients.

WISP: A prospective, multi-center trial of salpingectomy with delayed oophorectomy versus risk reducing salpingo-oophorectomy in women at increased risk for hereditary ovarian cancer

WISP: A prospective, multi-center trial of salpingectomy with delayed oophorectomy versus risk reducing salpingo-oophorectomy in women at increased risk for hereditary ovarian cancer

High-risk epithelial ovarian cancer patients for hereditary ovarian cancer.

Risk assessment to identify patients at risk for hereditary ovarian cancer is important. The objectives of this study were to evaluate the frequency of high-risk epithelial ovarian cancer (EOC) patients and the frequency of germline mutation in these patients. A total of 335 patients with histologically confirmed non-mucinous EOC were included. High-risk patients were defined as patients who had: (i) significant family history of breast/ovarian/colorectal/endometrial cancers; (ii) synchronous breast/endometrial/colorectal cancer; or (iii) high-grade serous carcinoma. Germline mutation was evaluated by Next Generation Sequencing system with the 27-genes panel. A total of 94 patients (28.1%) were high-risk patients, 5.1% had significant family history of cancers, 4.2% had synchronous primary cancers, and 22.1% had high-grade serous carcinoma. Germline mutation was detected in 10 of 35 patients (28.6%). Six germline mutations (17.1%) occurred in homologous recombination (HR) genes; these included three (8.6%) in BRCA1, one (2.9%) in BRCA2, and two (5.7%) in other HR genes (CHEK2 and RAD1C). Three patients (8.6%) had MMR gene mutations (one MLH1 and two MSH2) and one patient (2.9%) had other gene mutation (MUTYH). Of the 10 patients with germline mutation, 40% of patients had no significant family history of cancer. Up to 30% of EOC patients had risk factors for hereditary ovarian cancer. Germline mutation was identified in 28.6% of patients (11.4% BRCA mutation, 5.7% other HR genes mutation, 8.6% MMR mutation, and 2.9% mutation in other gene). The high cost of genetic testing is an important barrier. Selected patients with high-risk factors might be initially considered for genetic testing in a limited-resource setting.

Abstract P6-06-03: Novel hereditary breast cancer gene mutations: Should there be greater concern regarding ovarian cancer risk?

Abstract INTRODUCTION: As the use of multi-gene breast cancer panel testing increases the phenotype of the included genes continues to evolve. PALB2 and NBN have a well characterized association with breast cancer and are included on many breast cancer gene panels. Germline PALB2 and NBN mutations have been identified in a small percentage of ovarian carcinoma cases with one study reporting a non-significant twofold increase in carriers of the PALB2 mutations amongst ovarian cancer patients (P= 0.4). Similar to BRCA1 and BRCA2 both genes are members of the Fanconi Anemia pathway therefore a potential increased risk for both breast and ovarian cancer could be anticipated. However at present overall the current literature on the association with ovarian cancer is sparse. Here we present the cases of three hereditary breast and ovarian cancer families found to carry pathogenic mutations within the PALB2 and NBN genes. In all three families the proband was diagnosed with ovarian or fallopian tube cancer and carries a pathogenic PALB2 or NBN mutation. Our PALB2 family carries the well-known French Canadian founder mutation, c.2323C>T, and includes the proband who was diagnosed with a stage II-C, grade 3, fallopian tube carcinoma at age 58, her heterozygote sister with ovary cancer at 68 and her mother with ovary cancer at 43 who was not able to be tested. This PALB2 proband has 5 sisters, 7 brothers and 41 nieces and nephews with only one sister diagnosed with breast cancer at 69 who also is PALB2 positive and a maternal grandmother with breast cancer at 48 who was unable to be tested. The NBN Slavic founder mutation, c.657_661del, was discovered in a 66 year old woman with stage IV, high-grade serous ovarian cancer having a mother with breast cancer at 91 and a maternal aunt with ovary cancer at 59 who have not yet been tested. Lastly, our patient from Laos with a diagnosis of a stage II-C endometrioid adenocarcinoma of the ovary diagnosed at 38 years old was found to carry the deleterious NBN mutation, c.1550dupA. She is not aware of any cancer family history and reports a large family including five brothers, four sisters and multiple aunts and uncles on both side of the family. CONCLUSION: These case studies suggest a link between PALB2 and NBN, two known breast cancer susceptibility genes, and hereditary ovarian cancer risk. These observations suggest that further data are needed to accurately evaluate ovarian cancer risk within novel hereditary breast cancer genes now commonly tested as part of multiplex panel analysis. Citation Format: Nassikas N, Wilbur JS, Laprise JK, Legare RD. Novel hereditary breast cancer gene mutations: Should there be greater concern regarding ovarian cancer risk?. [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 P6-06-03.

Targeted Ovarian Cancer Education for Hispanic Women: A Pilot Program in Arizona.

In disadvantaged populations, including Hispanics, there is a deficit in understanding of cancer risk factors, symptoms, prevention, and treatment. The objective of this study was to assess ovarian cancer knowledge in a population of Hispanic women in Arizona, identify deficiencies, and to evaluate the utility of an educational program developed specifically for this community's needs. A de novo questionnaire about ovarian cancer was distributed to Hispanic women enrolled in family literacy programs at Mesa Public Schools. Following this assessment, a video educational program was developed, with emphasis on areas of greatest knowledge deficits, and post-intervention assessment administered. Chi square, Wilcoxon rank sum, and Kruskal-Wallis tests were used for analysis. 167 questionnaires were completed in the pretest group and 102 in the post-intervention group. Between groups, there were no differences in age (p=0.49), education (p=0.68), or annual income (p=0.26). In the pretest group, 45% of questions were answered correctly versus 84% in the post-test group (p<0.01). 24.2% of the initial respondents correctly identified ovarian cancer symptoms versus 85.6 of post-test respondents (p<0.01). With the program, there was an increase in the number of correct post-test responses for each question and symptom (p<0.01), except those about hereditary risk of ovarian cancer (p=0.62) and pelvic anatomy (p=0.16). Following identification of an ovarian cancer knowledge deficit in this cohort of Hispanic women, an educational tool targeting specific deficiencies successfully increased cancer knowledge and awareness of symptoms. Similar efforts in this and other minority populations should be continued.

Salpingectomy as a means to reduce ovarian cancer risk.

Bilateral salpingo-oophorectomy (BSO) has become the standard-of-care for risk reduction in women at hereditary risk of ovarian cancer. Although this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it affects quality of life, and the premature cessation of ovarian function may have long-term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high-grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review, we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy.

Misperceptions of ovarian cancer risk in women at increased risk for hereditary ovarian cancer

This study assessed the sociodemographic, medical and psychological predictors of accuracy of perceived risk in women at increased genetic risk for ovarian cancer. Women participating in a large cohort study who were at increased risk of ovarian and fallopian tube cancer, had no personal history of cancer and had ≥1 ovary in situ at cohort enrollment, were eligible. Women completed self-administered questionnaires and attended an interview at enrollment. Of 2,868 women unaffected with cancer at cohort enrollment, 561 were eligible. 335 women (59.8 %) overestimated their ovarian cancer risk, while 215 women (38.4 %) accurately estimated their risk, and 10 (1.8 %) underestimated it. Women who did not know their mutation status were more likely to overestimate their risk (OR 1.74, 95 % CI 1.10, 2.77, p = 0.018), as were those with higher cancer-specific anxiety (OR 1.05, 95 % CI 1.02, 1.08, p < 0.001) and/or a mother who had been diagnosed with ovarian cancer (OR 1.98, 95 % CI 1.23, 3.18, p = 0.005). Amongst the group of women who did not know their mutation status, 63.3 % overestimated their risk and the mean perceived lifetime risk of developing ovarian cancer was 42.1 %, compared to a mean objective risk of 6.4 %. A large number of women at increased risk for ovarian cancer overestimate their risk. This is of concern especially in women who are at moderately increased risk only; for this sub-group of women, interventions are needed to reduce potentially unnecessary psychological distress and minimise engagement in unnecessary surgery or screening.

Analysis of RAD51D in ovarian cancer patients and families with a history of ovarian or breast cancer.

Mutations in RAD51D have been associated with an increased risk of hereditary ovarian cancer and although they have been observed in the context of breast and ovarian cancer families, the association with breast cancer is unclear. The aim of this current study was to validate the reported association of RAD51D with ovarian cancer and assess for an association with breast cancer. We screened for RAD51D mutations in BRCA1/2 mutation-negative index cases from 1,060 familial breast and/or ovarian cancer families (including 741 affected by breast cancer only) and in 245 unselected ovarian cancer cases. Exons containing novel non-synonymous variants were screened in 466 controls. Two overtly deleterious RAD51D mutations were identified among the unselected ovarian cancers cases (0.82%) but none were detected among the 1,060 families. Our data provide additional evidence that RAD51D mutations are enriched among ovarian cancer patients, but are extremely rare among familial breast cancer patients.

Psychological Sequelae of Ovarian Cancer Screening and Genetic Testing for Ovarian Cancer Susceptibility

Ovarian cancer is the most lethal of gynaecological malignancies. Although early detection efforts have been relatively unsuccessful in reducing mortality at the population level, ovarian cancer screening continues to be offered to some women. Testing for mutations in the BRCA1/2 genes can determine whether women have a heightened risk of developing ovarian cancer and those found to be at high risk are closely followed and offered cancer risk-reducing strategies. Yet, ovarian cancer screening and genetic testing have potential psychological sequelae. The purpose of this article is to present an overview of these psychological sequelae. Overall, women who receive normal ovarian cancer screening results benefit emotionally and the emotional distress associated with abnormal results subsides once a cancer diagnosis is excluded. There are psychological benefits of genetic testing as well as potential challenges that include interpreting results, feelings of anxiety, distress and depression, changes in self-concept, experiencing guilt and worry regarding family members, communicating with family and making decisions about ovarian cancer screening and riskreducing oophorectomy. Psychological support that addresses the unique psychological sequelae associated with hereditary ovarian cancer risk and targets the subgroup of women who are more likely to experience difficulties would likely be beneficial. Keywords: Ovarian cancer, screening, genetic testing, psychological, women's health, gynaecological malignancies, BRCA1/2 testing, oophorectomy, women's psychological health, biomarker screening

Inefficacité du dépistage des cancers tubo-ovariens dans les situations de risque héréditaire de cancer de l’ovaire ; l’expérience du Centre Oscar-Lambret

As part of a study in the North of France for screening pelvic tumours with plasma proteomic analysis, we included 82 women with hereditary risk of ovarian cancer. We report here the consequences of organized screening with usual tests. CA 125 sampling and a transvaginal pelvic ultrasound by a radiologist were systematically conducted every 6 months. Seventy-two patients were eventually evaluable. Two incident cases of peritoneal carcinomatosis (FIGO IIIB, malignant epithelial serous high-grade tumors) were discovered in two asymptomatic women with a deleterous BRCA1 mutation (2.7%). We did not observe any other primary cancer cases but an ovarian metastasis of a breast cancer. Forty women went off the study: 32 had a prophylactic bilateral salpingo-oophorectomy. Consistent with the literature, biannual screening tests combining CA125 and pelvis ultrasound is ineffective for early detection of a pelvic tumor of tubal or ovarian origin. Testing for BRCA1 or BRCA2 deleterious mutations is then crucial for suspected family syndromes of breast and ovarian cancer. For women carrying a deleterous mutation on BRCA1/2 a salpingo-oophorectomy is the only way, only the time of this surgery is debatable.

New Strategies in Ovarian Cancer: Uptake and Experience of Women at High Risk of Ovarian Cancer Who Are Considering Risk-Reducing Salpingo-Oophorectomy

Here, we review factors associated with uptake of risk-reducing salpingo-oophorectomy by women at increased hereditary risk for ovarian cancer, as well as quality of life issues following surgery. Forty-one research studies identified through PubMed and PsychInfo met inclusion criteria. Older age, having had children, a family history of ovarian cancer, a personal history of breast cancer, prophylactic mastectomy, and BRCA1/2 mutation carrier status increase the likelihood of undergoing surgery. Psychosocial variables predictive of surgery uptake include greater perceived risk of ovarian cancer and cancer-related anxiety. Most women report satisfaction with their decision to undergo surgery and both lower perceived ovarian cancer risk and less cancer-related anxiety as benefits. Hormonal deprivation is the main disadvantage reported, particularly by premenopausal women who are not on hormonal replacement therapy (HRT). The evidence is mixed about satisfaction with the level of information provided prior to surgery, although generally, women report receiving insufficient information about the pros and cons of HRT. These findings indicate that when designing decision aids, demographic, medical history, and psychosocial variables need to be addressed in order to facilitate quality decision making.

Intercepting early pelvic serous carcinoma by routine pathological examination of the fimbria

Recent evidence indicates that the distal fallopian tube is the principal site of early serous cancer in women with a hereditary risk for ovarian cancer. Moreover, the fimbria is involved by early cancer in a significant minority of pelvic serous carcinomas, irrespective of whether the patient has a hereditary BRCA1 or BRCA2 mutation. In addition, the distal tube has been identified occasionally as a site of concurrent endometrioid tumors in women with endometrial carcinoma. Although the risk of sporadic fimbrial tumors in otherwise healthy women without genetic risk is unknown, routine histological examination of the fimbria provides the opportunity to determine the risk of such an event. To illustrate this point, a case of a woman who underwent surgery for an ovarian fibroma is presented. The distal tube was submitted, and found to harbor a focus of serous tubal intraepithelial carcinoma (STIC) with a 2-mm invasive tumor. Incidentally discovered carcinomas underscore the potential risk, albeit low, of concurrent unsuspected malignancy in the distal fallopian tube and emphasize the importance of routine pathological examination of the fimbria in all salpingectomies. The rationale for this strategy, and its potential effect on early detection and in uncovering persons or families potentially at risk for ovarian cancer, is discussed.

Ovarian cancer risk in Polish BRCA1 mutation carriers is not associated with the prohibitin 3' untranslated region polymorphism

BackgroundThe variable penetrance of ovarian cancer in BRCA1 mutation carriers suggests that other genetic or environmental factors modify disease risk. The C to T transition in the 3' untranslated region of the prohibitin (PHB) gene alters mRNA function and has recently been shown to be associated with hereditary breast cancer risk in Polish women harbouring BRCA1 mutations.MethodsTo investigate whether the PHB 3'UTR polymorphism also modifies hereditary ovarian cancer risk, we performed a case-control study among Polish women carrying one of the three common founder mutations (5382insC, 300 T > G, 4154delA) including 127 ovarian cases and 127 unaffected controls who had both breasts and ovaries intact. Controls were matched to cases by year of birth and BRCA1 mutation. Genotyping analysis was performed using PCR-based restriction fragment length polymorphism analysis. Odds ratios (OR) were calculated using conditional and penalized univariable and multivariable logistic regression.ResultsA comparison of the genotype frequencies between cases and controls revealed no association of the PHB 3'UTR _CT+TT genotypes with ovarian cancer risk (ORadj 1.34; 95% CI, 0.59–3.11).ConclusionOur data suggest that the PHB 3'UTR polymorphism does not modify ovarian cancer risk in women carrying one of the three Polish BRCA1 founder mutations.

High percentage of abnormal findings on TVU needs further discussion

Sir, With great interest, we read the publication ‘Surveillance of women at high risk for hereditary ovarian cancer is inefficient' published by Oei et al (2006) in your journal. The authors evaluated the efficacy of 10-year gynaecological surveillance in 512 women at risk for hereditary ovarian cancer in a tertiary referral centre. This gynaecological surveillance included annual pelvic examination, transvaginal ultrasound (TVU) and serum CA125 measurements. In case of abnormal findings in at least one of the surveillance tests, revision of the abnormal test after 3–6 months was advised. A total of 1621 surveillance tests were performed. In 317 contacts (21%), TVU showed abnormal findings. Of these, 295 (93%) were not present during repeat TVU after 3–6 months. Because only two cases of ovarian cancer were diagnosed during this annual surveillance, it can be calculated that the highest estimate for a positive predictive value of an abnormal TVU is 0.6%. This figure of 21% abnormal findings on TVU needs further discussion than the authors give in this paper. The criteria in the method section of this study, according to which TVU was considered as abnormal were: multiple cysts, cysts with thick septa, papillary projection, irregular patterns or a variety in sonolucency. In the discussion section, the authors explain their high percentage of false-positive findings on TVU with the observation that the majority of their patients were premenopausal and that a variety of benign conditions (e.g. follicle cysts) have contributed to the high incidence of normalising abnormalities. It is remarkable that the list of criteria used in this study according to which TVU was considered abnormal, does not include the presence and/or size of monolocular cysts. According to the Sassone criteria, only cysts of more than 6 cm need further investigation in premenopausal women (Sassone et al, 1991). A second point of attention is that it is not mentioned whether the authors found any adverse effects in this group of patients who had to wait for 3–6 months before they could be reassured by a repeat TVU. It is known from literature that ovarian cancer screening in high-risk women can have a great impact on the anxiety score, especially of premenopausal women (Hensley et al, 2003). We agree with the authors that surveillance is highly ineffective to detect early ovarian (tubal) cancer in high-risk women. It can be questioned whether their suggestion to conduct a study with a larger group of BRCA mutation carriers with a longer follow-up is in line with this conclusion. However, if they need more definitive conclusions, as they suggested, they should define their TVU criteria more precisely in order to avoid this high percentage of false-positive TVU findings and the high loss of quality of life in women with a false-positive TVU finding.