BRCA1 mutation testing for Japanese patients with ovarian cancer in breast cancer screening

From February 1996 to April 1998, 2967 women received screening for breast cancer in the gynecologic ambulatory practice of the Hokkaido University Hospital. In 116 Japanese women with epithelial ovarian cancer, mutation analysis of BRCA1 exon 11 in genomic DNA was performed by the stop codon (SC) assay and DNA sequence analysis. Clinicopathological factors were also investigated in these patients. The aim of this study was to examine the advantages of performing BRCA1 mutation testing for ovarian cancer patients during breast cancer screening. We achieved a high detection rate (6.0) of patients with germline mutations in BRCA1. The high frequencies of breast ovarian cancer syndrome, serous adenocarcinoma, high histological grades, advanced FIGO stages, and breast cancer as double cancer were found to be characteristic of ovarian cancer with germline mutations in BRCA1. These characteristics may assist physicians in selecting BRCA1 mutation testing for ovarian cancer patients. The mean age at diagnosis of ovarian cancer was 51.0 and 51.2 years in the groups with and without mutation, respectively, and no difference was found in age at diagnosis. All of the nine living female mutation carriers were offered the options of increased surveillance or prophylactic surgery, and all chose the former. We have performed breast cancer screening and/or ovarian cancer screening every 6 months for these carriers. This may allow another advantage in establishing a relationship of mutual trust with a patient from a series of responsible follow-ups.     

Effects of screening for breast cancer on its age-incidence relationships and familial risk

Mammographic screening programs for breast cancer have been implemented in many countries and opportunistic mammographies are taken as a diagnostic method. The consequences of the wide application of this technology to age-incidence relationships in breast cancer have not been clarified nor is its effect on familial risk estimation. It was assumed that if screening and diagnostic methods bias familial risk, the highest risk should be noted for sisters diagnosed close in time. Age-specific incidence data were collected from the EUCAN database and from cancer registries of Finland, Norway and Sweden. The Swedish Family-Cancer Database was used to analyse risks for breast cancer among sisters, depending on the time since the first sister was diagnosed with breast cancer. Age-incidence patterns deviated between Germany, with low mammographic coverage, and Sweden, the Netherlands, the UK and France, with variable levels of coverage. The annual age-incidence patterns in Finland, Norway and Sweden changed in concert with the targeted mammographic service. The risk of breast cancer for women with an affected sister, diagnosed between ages 50 to 64 years, was significantly higher within the same or the subsequent year of the sister's diagnosis compared to 5+ years, accounting for 7.3% of all patients. The ordered increase in age-specific incidence of breast cancer in the women targeted by screening studied suggests that mammographic screening is one important factor responsible for the shift of the age of onset for breast cancer towards middle age. However, the effects on the estimation of familial risk are so far small.     

The relationship between coping strategies and anxiety in women from families with familial breast-ovarian cancer in the absence of demonstrated mutations

This is a cross-sectional study of coping strategies in 174 healthy women who fulfill clinical criteria for familial breast/ovarian cancer in the absence of demonstrated mutations (ADM) compared to 68 healthy women with BRCA1 carrier status. Both groups got a mailed questionnaire after genetic counseling and testing, respectively. The questionnaire included demographic and cancer-related variables as well as the Hospital Anxiety and Depression Scale (HADS) and the Coping Orientation to Problems Experienced Scale (COPE). In both groups 24% of the women had an anxiety disorder. Coping strategies which helped the women to accept and make the best out of their situation were most frequently applied in both the ADM and the carrier groups. Compared to the carrier group, the ADM group had higher mean levels on both emotion-focused and problem-focused strategies. The emotion-focused strategies were all significantly associated with presence of HADS-defined anxiety disorder in the ADM group. In the carrier group problem-focused strategies were significantly associated with increased prevalence of such anxiety disorder. In multivariate analysis 'focus on emotions' was significantly associated with increased prevalence of HADS-defined anxiety disorder in both groups, and 'acceptance' was associated with reduced prevalence in both groups.     

First experiences in screening women at high risk for breast cancer with MR imaging

Women with a genetic predisposition for breast cancer are often advised surveillance with physical examination twice a year and mammography once a year from 25 years onwards. However, the sensitivity of the mammography decreases when breast tissue is dense and this is seen in 40–50% of women under 50 years. We therefore investigated whether magnetic resonance imaging (MRI) in addition to the normal surveillance could detect cancers otherwise missed. In 109 women with over 25% risk of breast cancer, MRI was performed because over 50% dense breast tissue was seen at mammography and no suspect lesion was seen at the previous screening. MRI detected breast cancers in three patients (2.8%) occult at mammography and with no new palpable tumor, twice at stage T1bN0 and T1cN0 once. Two cancers were expected. MRI was false positive in six women, resulting in two benign local excisions because ultrasound or fine needle examination confirmed suspicion. We had no false negative MRI results. MRI proved true benign in four BRCA 1/2 gene mutation carriers at histologic examination. Preoperative wire localization of the malignancies detected at MRI proved necessary as the tumor was not palpable in the lumpectomy specimen nor visible at specimen radiology. The extra cost of breast MRI in addition to mammography and physical examination was uro13.930 per detected cancer. The cost of the detection of one breast cancer patient in our national screening program is uro9000. During follow-up of patients with a familial risk in whom the first breast cancer was detected at MRI, MRI detected two recurrent cancers in stage T1bN0 and T1cN0 and one contralateral cancer T1aNo. Breast MRI is promising in screening young women at high risk for breast cancer, as it can advance the detection of cancers still occult at mammography and physical examination; but the cost may be considerable.     

Patient delay in oral cancer: a qualitative study of patients' experiences

Up to 30% of patients delay seeking the advice of a healthcare professional after self-discovery of symptom(s) of oral cancer. Reasons for this patient delay are poorly understood. The aim of the present study was to explore patients' initial experiences and reactions to developing symptoms of oral cancer, and to identify factors influencing their decision to consult a health care professional. In-depth semi-structured interviews were conducted with 17 consecutive patients who had received a diagnosis of oral squamous cell carcinoma, but had yet to start treatment. Participants were asked about their beliefs about their symptoms over the course of the disease and their decision to seek help. The tape-recorded interviews were transcribed verbatim and analysed using 'Framework analysis'. Oral symptoms were rarely attributed to cancer and were frequently interpreted as minor oral conditions. As a result of these beliefs, patients tended to postpone seeking help or fail to be concerned over their symptoms. Prior to seeking help, patients responded to symptoms by using self-medication, changing the way they ate and disclosing their discovery of symptoms to friends or family. Problems with access to healthcare professionals and patients' social responsibilities acted as barriers to prompt help-seeking. This study has documented that an individual's interpretation of oral cancer symptoms may be misguided and this can adversely affect subsequent help-seeking behaviour.     

It's a choice to move forward: women's perceptions about treatment decision making in recurrent ovarian cancer

Objective: This research explores the treatment decision‐making (TDM) experiences of women with recurrent ovarian cancer (ROC) with regard to treatment options; their understanding of risks and benefits of various treatment options; the decision‐making role they want for themselves and for their oncologist; and the social context of the consultation as it pertains to the decision. Methods: We conducted semi‐structured interviews with 26 women at the time of first recurrence. Through inductive data analysis key themes were identified. Results: Many women describe self‐identifying the cancer recurrence fairly quickly due to new symptoms. Many feel that the goal for treating their recurrence is to control versus cure the cancer. They describe the subsequent process of diagnosis and TDM for ROC as quick and straightforward with all women accepting the oncologists' treatment recommendation. They feel that the type and number of treatment options are limited. They have a strong desire for physician continuity in their care. Participants feel that their doctor's recommendations as well as their previous experience with ovarian cancer are strong factors influencing their current TDM process. Conclusions: Shared decision making is based on a simultaneous participation of both the physician and patient in TDM. When faced with ROC, women feel that their doctor's recommendation and their past experience with treatment and TDM are prominent factors influencing the current TDM process. Copyright © 2009 John Wiley & Sons, Ltd.     

Changes in cancer worry associated with participation in ovarian cancer screening

While ovarian cancer is rare and screening is not recommended for most women, it is being studied as a way to reduce ovarian cancer mortality. As effective strategies for screening emerge it will be important to understand the quality of life (QOL) effects of participation in ovarian cancer screening. In this study, we examined the effects of participation in an ovarian cancer screening program on worry about cancer risk and QOL. A randomized controlled clinical trial (n = 592) was conducted. Women without a family history suggestive of a BRCA1/2 mutation were randomly assigned to screening and risk counseling, separately and in combination. Results were compared to women randomized to usual care alone. Levels of cancer worry fell for all study groups and QOL was unaffected; no statistically significant differences were found between groups. Increased levels of worry about ovarian cancer at 2-year follow-up were found among participants in screening receiving abnormal test results. For those who receive abnormal results, screening may have long-term effects and increase worry about cancer risk. Further research will be required to examine the possibility that screening reduces worry when women receive only normal, presumably reassuring, results.     

Whole blood-derived miRNA profiles as potential new tools for ovarian cancer screening

Background:

Screening is an unsolved problem for ovarian cancer (OvCA). As late detection is equivalent to poor prognosis, we analysed whether OvCA patients show diagnostically meaningful microRNA (miRNA) patterns in blood cells.

Methods:

Blood-borne whole miRNome profiles from 24 patients with OvCA and 15 age- and sex-matched healthy controls were biostatistically evaluated.

Results:

Student''s t-test revealed 147 significantly deregulated miRNAs before and 4 after Benjamini–Hochberg adjustment. Although these included miRNAs already linked to OvCA (e.g., miR-16, miR-155), others had never before been connected to specific diseases. A bioinformatically calculated miRNA profile allowed for discrimination between blood samples of OvCA patients and healthy controls with an accuracy of >76%. When only cancers of the serous subtype were considered and compared with an extended control group (n=39), accuracy, specificity and sensitivity all increased to >85%.

Conclusion:

Our proof-of-principle study strengthens the hypothesis that neoplastic diseases generate characteristic miRNA fingerprints in blood cells. Still, the obtained OvCA-associated miRNA pattern is not yet sensitive and specific enough to permit the monitoring of disease progression or even preventive screening. Microarray-based miRNA profiling from peripheral blood could thus be combined with other markers to improve the notoriously difficult but important screening for OvCA.     

Psychosocial impact of the lack of information given at referral about familial risk for cancer

We aimed to identify patient' information and communication needs irrespective of their risk level, when they are referred for genetic risk assessment and genetic counselling for a predisposition to cancer. Semi-structured telephone interviews were conducted with a purposive sample of individuals referred to a clinical genetics unit for a risk assessment of their genetic predisposition to either breast, ovarian or colorectal cancer and stratified by their level of risk. Triangulation was achieved by focus groups conducted with specialist genetic health professionals. Twenty-three participants were interviewed pre- and post-genetic counselling or risk assessment. A further 11 completed a single interview, five pre-assessment and six post-assessment. Three focus groups were conducted with the genetic health professionals. The results showed that many participants were unaware they had been referred for genetic counselling and as a consequence they felt this caused difficulties in coping with the genetic risk information received. Health professionals corroborated these findings of people's lack of awareness about their referral. This work raises important questions about the psychosocial consequences of inadequate information provision at the point of referral by clinicians in primary and hospital-based healthcare that are responsible for referring the majority of people to clinical genetics units.     

遗传性卵巢癌基因筛查及家族成员管理研究进展

卵巢癌是发生率居于全球女性第三位、死亡率居于首位的妇科恶性肿瘤,其中10%~15%由胚系突变导致,称为遗传性卵巢癌（hereditary ovarian cancer）。遗传性卵巢癌是一种常染色体显性遗传病,它的发生与BRCA1/2等基因突变有关。对家族中的先证者进行基因检测,识别卵巢癌易感基因胚系突变,鉴定遗传性卵巢癌,可以使患者受益于个性化治疗,同时提示家庭成员进行基因筛查,以找出家族中高危致病基因突变的携带者,对携带者实施肿瘤的早期监测和干预。这对于降低疾病发病率和死亡率,改善长期预后有重要临床意义。本文总结现有文献,并就遗传性卵巢癌家族成员基因筛查中的主要基因相关临床意义和管理策略进行综述。