BRCA Gene Mutation Carriers Research Articles

Un enfoque de terapia ocupacional adaptada a la rehabilitación cognitiva de los efectos cognitivos colaterales asociados a la quimioterapia en pacientes supervivientes de cáncer de mama: dos estudios de mujeres postmenopáusicas afectadas

This article describes a tailored occupational therapy program to rehabilitate chemotherapy-related cognitive side effects. A literature review of cognitive rehabilitation as well as pharmacological trials used to improve cognition in breast cancer patients is included. Two outpatient case studies of young women premenopausally affected with breast cancer (both BRCA-1 gene mutation carriers) are used to discuss the role of tailored occupational therapy techniques for developing compensatory strategies and for delivering cognitive remediation. Neuropsychological evaluation pre and post occupational therapy is used to document the result of tailored occupational therapy on cognitive performance. The case studies illustrate the neuropsychological profile of chemotherapy-related cognitive changes and the course of deficits over 7-9 months. For younger, educated patients who must return to competitive, fast-paced jobs, cognitive side-effects post-treatment are especially noxious as young adult patients are building their professional lives and are not necessarily provided time to wait for the usual trajectory of recovery to take its course.

Arsenic (As) and breast cancer risk

The study was conducted to determine the correlations between serum concentration of arsenic (As) with increased or decreased predisposition to breast and ovarian cancer.

A functional assay for the identification of DNA double-strand break repair deficiency in heterozygous carriers of BRCA1/2 and RAD51C mutations.

561 Background: Mutations in breast cancer gene 1 and 2(BRCA1/2) account for 50% of the familial aggregation of breast and ovarian cancer. About one third of the mutations are of unknown pathogenetic relevance (unclassified variants, UCV). We recently identified RAD51C as a third high penetrance gene (Meindl et al., 2010). Like BRCA1/2, RAD51C is also involved in homologous recombination repair (HRR) in response to DNA double strand breaks. It has recently been shown that cells with HRR deficiency are sensitive to synthetic lethality mediated by PARP inhibition. Under the assumption that further high risk genes may exist which acts through the HRR pathway we aimed to develop a reliable functional test system which allows the evaluation of HRR deficiency in heterozygous carriers. Methods: We included eight carriers of a pathogenic BRCA2 mutation, two carriers of a pathogenic RAD51C mutation and nine healthy controls as well as seven BRCA2 UCV carriers. Patient and control lymphocytes were γ-irradiated in G2 phase to introduce DNA-DSB. For the assessment of HRR capacity, metaphase chromosomes were stained by multicolour fluorescence in situ hybridisation (M-FISH). Chromosomal translocations and breakages were counted per mitosis and referred to total chromosomal number. The aberration frequency of BRCA2 and RAD51C carriers versus the controls was compared. Results: Lymphocytes from BRCA2 and RAD51C pathogenic mutation carriers versus controls showed a mean aberration frequency of 2.51±0.36 (standard deviation, SD) and 2.7±0.25 (SD), respectively, versus 1.4±0.44 (SD) chromosomal aberrations per metaphase with no overlap (p-value <0.001; Student’s t-test). Seven patients carrying an UCV in BRCA2 could be allocated to either the pathogenic or the control group. Conclusions: Our test system allows the detection of HRR deficiency in heterozygous lymphocytes of BRCA2 and RAD51C gene mutation carriers and is currently evaluated in BRCA1 positive cases. The assay may enable the identification of HRR deficiency irrespective of the underlying gene defect and may also serve as a biomarker for sensitivity to PARP inhibition.

De relatie tussen genetisch onderzoek, psychologisch welbevinden en medisch handelen Een vragenlijststudie bij vrouwelijke en mannelijke presymptomatische dragers en niet-dragers van een BRCA-genmutatie

The relationship between genetic testing, psychological well-being and surveillance behavior: A questionnaire study in presymptomatic female and male BRCA carriers and non-carriers. Many researchers have investigated the impact of BRCA gene testing on psychological well-being, but results are equivocal. Heterogeneous findings may point to the role of influencing factors. The current questionnaire study investigates the relationship between genetic testing, psychological wellbeing, and surveillance behavior. The role of sex, age, SES, carrier status, time since testing, number of children, and coping is examined. The research sample consists of 119 presymptomatic BRCA gene mutation carriers and non-carriers (Mage=41.71,SD=11.05). Results indicated that genetic testing is related to psychological well-being over time.Women report more distress than men, carriers more than non-carriers. Coping at the moment of the genetic testing also influences psychological well-being over time. The more people used an emotion-oriented and problem-oriented coping style at the moment of testing, the lower their psychological well-being over time. Results furthermore indicated that surveillance behavior is predicted by sex, carrier status, number of children and problem-oriented coping. Carrier status is the only predictor of prophylactic surgery. Results of this study may contribute to the identification of persons at-risk for lower levels of psychological well-being and surveillance behavior.

Cost-effectiveness of Breast MR Imaging and Screen-Film Mammography for Screening BRCA1 Gene Mutation Carriers

Cost-effectiveness of Breast MR Imaging and Screen-Film Mammography for Screening BRCA1 Gene Mutation Carriers

Pyoderma Gangrenosum Following Bilateral Deep Inferior Epigastric Perforator Flap Breast Reconstruction

Pyoderma gangrenosum (PG) is a relatively rare condition of ulcerative cutaneous dermatosis. Usually seen in the setting of systemic inflammatory disease, PG can be difficult to distinguish from infection. We present a case of an otherwise healthy 37-year-old woman, a BRCA-1 gene mutation carrier, who was evaluated several months after bilateral mastectomies with deep inferior epigastric perforator (DIEP) flap breast reconstruction with open wounds on the right DIEP flap. Multiple interventions were employed without success. As the disease progressed, the patient eventually developed new open wounds on the left DIEP flap as well. Ultimately, rigorous dermatopathology evaluation revealed PG, and the patient was treated appropriately with a high-dose prednisone course. The wounds healed completely, and despite significant cutaneous scarring, the breast reconstructions were salvaged. There was no fat necrosis within the DIEP flap tissue itself. PG should be considered in the differential diagnosis of chronic nonhealing cutaneous ulcers following surgical intervention that do not respond to standard initial care.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of PENN II model to previous study

A number of models have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is variable. To compare the performance characteristics of a web-based BRCA1/BRCA2 gene mutation prediction model: the PENNII model ( www.afcri.upenn.edu/itacc/penn2 ), with studies done previously at our institution using four other models including LAMBDA, BRCAPRO, modified PENNI (Couch) tables, and Myriad II tables collated by Myriad Genetics Laboratories. Proband and family cancer history data were analyzed from 285 probands from unique families (27 Ashkenazi Jewish; 277 female) seen for genetic risk assessment in a multispecialty tertiary care group practice. All probands had clinical testing for BR.CA1 and BRCA2 mutations conducted in the same single commercial laboratory. The performance for PENNII results were assessed by the area under the receiver operating characteristic curve (AUC) of sensitivity versus 1-specificity, as a measure of ranking. The AUCs of the PENNII model were higher for predicting BRCA1 than for BRCA2 (81 versus 72%). The overall AUC was 78.7%. PENN II model for BRCA1/2 prediction performed well in this population with higher AUC compared with our experience using four other models. The ease of use of the PENNII model is compatible with busy clinical practices.

“The Bigger the Network the Bigger the Bowl of Cherries…”: Exploring the Acceptability of, and Preferences for, an Ongoing Support Network for Known BRCA 1 and BRCA 2 Mutation Carriers

There is increasing evidence to suggest that the ongoing information and support needs of BRCA gene mutation carriers are not being met. This qualitative study investigated preferences for an on-going support network for mutation carriers in Wales, UK. Seventeen female BRCA1/2 mutation carriers participated in focus groups which explored their current and on-going information and psychological support needs. The interviews were transcribed and thematically analysed. The results reflected a diversity of experiences and support needs. The majority of participants felt they and their families would benefit from an on-going 'support network' which should incorporate information-provision alongside elements of a traditional support group alongside, internet-based support such as web-based chat forums, matching schemes and professionally led workshops. Some degree of professional input into any such initiative was believed to be important. This study has informed the development of an appropriate support network based on a hub and spoke model to help carriers and their families adapt to living and coping with their genetic risk.

Characteristics, Treatment, and Outcome of Breast Cancers Diagnosed in BRCA1 and BRCA2 Gene Mutation Carriers in Intensive Screening Programs Including Magnetic Resonance Imaging

Background Breast magnetic resonance imaging (MRI) with conventional screening methods improves sensitivity in high-risk patients without benefits on specific survival. We evaluated the characteristics, treatments, and prognostic features of breast cancers diagnosed among BRCA1/2 mutation carriers either inside or outside screening programs that included MRI. Patients and Methods Two groups of patients diagnosed with a new breast cancer between 2001 and 2007 were compared: group 1, patients included in an intensive screening program; and group 2, patients outside of this program. Results Twenty-one patients met inclusion criteria for group 1, and 102 for group 2. Seventy-four percent and 65%, respectively, were BRCA1 mutation carriers. Tumors in both groups had the same characteristics (pN, grade, estrogen receptor, progesterone receptor, HER2 expression), except for smaller tumor size in group 1 (median, 6 mm vs. 22 mm; P < .0001). Group 1 patients had more frequent sentinel node procedures (57% vs. 28%; P = .021) and less commonly received chemotherapy (43% vs. 86%; P < .0001). The 3-year disease-free survival (93% vs. 74%; P = .1) and the 3-year overall survival (100% vs. 92%; P = .2) did not differ between groups. Conclusion MRI might provide improvement in BRCA1/2 carriers in terms of smaller tumor size and treatment morbidity. However, because of aggressive intrinsic characteristics, this does not turn into significant survival benefits.

Excretion of estrogens, catecholestrogens and phytoestrogens in carriers of BRCA1 gene mutations: effects of metformin

BRCA1 gene mutation is associated with a combination of excessive aromatase activity/expression, predominantly estrogen receptor-negative phenotypes of tumors, and only scarce information about estrogen contents in body fluids. In the present work, isotope dilution capillary gas chromatography/mass spectrometry was used to study urinary excretion of estrogens, their catechol metabolites, and phytoestrogens in 22 women (11 with BCRA1 gene mutations and 11 without these mutations) in average 5.1+/-0.4 years before surgery for breast cancer. BCRA1 mutation carriers (including 3 premenopausal females) compared with respective controls showed significantly higher urinary estradiol and estrone excretion and a trend to an increased 2-OH-E2 excretion. In the subgroup of untreated postmenopausal women, BCRA1 mutation carriers showed a trend to increased estradiol and estrone excretion and to a higher value of the mean levels of all estrogen metabolites tested. The treatment after the baseline laboratory investigation of 6 women from postmenopausal group with the antidiabetic biguanide metformin for 3 months was associated with decreases in the excretion rates of 4-hydroxyestradiol, 2-methoxyestradiol, and 16-epiestriol and did not influence phytoestrogen excretion. The decrease in 2-methoxyestrogen excretion was more consistent in women without BCRA1 mutations than in BCRA1 mutation carriers. The data suggest the possibility that aromatase complex activation in BCRA1 mutation carriers is combined with increases in both, estrogen metabolism into catecholestrogens and their inactivation by methoxylation, and that metformin may affect both of these pathways.

Cancers inBRCA1andBRCA2Carriers and in Women at High Risk for Breast Cancer: MR Imaging and Mammographic Features

To review imaging features of screening-detected cancers on images from diagnostic and prior examinations to identify specific abnormalities to aid earlier detection of or facilitate differentiation of cancers in BRCA1 and BRCA2 carriers and in women with a high risk for breast cancer. Informed consent and multicenter and local research ethics committee approval were obtained. Women (mean age, 40.1 years; range, 27-55 years) who had at least a 50% risk of being a BRCA1, BRCA2, or TP53 gene mutation carrier were recruited from August 1997 to March 2003 into the United Kingdom Magnetic Resonance Imaging in Breast Screening Study Group trial and were offered annual magnetic resonance (MR) imaging and two-view mammography (total number of screenings, 2065 and 1973; mean, 2.38 and 2.36, respectively). Images in all 39 cancer cases were reread in consensus to document the morphologic and enhancement imaging features on MR and mammographic images in screening and prior examinations. Cases were grouped into genetic subtypes. With MR imaging, there was no difference in morphologic or enhancement characteristics between the genetic subgroups. Cancers on images from prior examinations were of smaller size, showed less enhancement, and were more likely to have a type 1 enhancement curve compared with those cancers in the subsequent diagnostic screening examinations. The tumor sizes detected by using MR imaging and mammography were not significantly different (P = .46). The cancers in BRCA1 carriers found by using MR imaging tended to be smaller than those detected by using mammography (median, 17 mm vs 30 mm; P = .37), whereas the opposite was true for cancers found in BRCA2 carriers (MR imaging median size = 12.5 mm vs mammographic median size = 6 mm; P = .067); the difference was not significant. Tumors with prior MR imaging abnormalities grew at an average of 5.1 mm/y. When undertaking MR imaging surveillance in high-risk women, small enhancing lesions should be regarded with suspicion and biopsied or patients should be followed up at 6 months.

Intensivierte Vorsorge bei familiärer Disposition für Brustkrebs – Eigene Ergebnisse und derzeitiger Stand

Fragestellung: Evaluation eines intensivierten Vorsorgeprogramms zur Brustkrebsfrüherkennung bei Frauen mit familiärer Disposition für Brustkrebs. Material und Methodik: In der vorliegenden prospektiven Studie wurden 157 Frauen untersucht. Einschlusskriterium war eine molekulargenetisch nachgewiesene BRCA-1-Mutation (n = 33), BRCA-2-Mutation (n = 14) oder ein Heterozygotenrisiko ≥ 20 % bzw. ein Lebenszeiterkrankungsrisiko ≥ 30 % (n = 110). Die Ergebnisse wurden getrennt nach gesunden Ratsuchenden (n = 75) und bereits an Brust- bzw. Eierstockkrebs erkrankten Teilnehmerinnen (n = 82) evaluiert. Das Studienprotokoll beinhaltet halbjährlich eine ärztliche klinische Untersuchung und Sonografie sowie jährlich eine Mammografie und MR-Mammografie. Ergebnisse: Bei 12 Frauen wurde im Überwachungszeitraum (1. 11. 1999 – 31. 10. 2007) histologisch ein Mammakarzinom nachgewiesen, wobei 75 % der Karzinome in einem pT1-Stadium bzw. 89 % im pN0-Stadium diagnostiziert wurden. Folgende diagnostische Kennzahlen wurden ermittelt. Sensitivität: klinische Untersuchung 25 %, Mammografie 27 %, Sonografie 58 %, MR-Mammografie 100 %; positiver Vorhersagewert: klinische Untersuchung 75 %, Mammografie 38 %, Sonografie 50 %, MR-Mammografie 60 %; Spezifität: klinische Untersuchung 99,8 %, Mammografie 99,6 %, Sonografie 99,0 %, MR-Mammografie 97,6 %. Insgesamt korrelieren diese Daten gut mit den Ergebnissen nationaler und internationaler Studien. Die Karzinomdetektionsrate und der positive Vorhersagewert waren bei den BRCA-1-Mutationsträgerinnen am höchsten. Schussfolgerung: Basierend auf den vorliegenden Daten der Forschungsliteratur erlauben intensivierte Vorsorgeprogramme bei Frauen mit familiärer Disposition für Brustkrebs eine Karzinomdetektion in einem frühen Tumorstadium. Die MR-Mammografie ist bei den eingesetzten Verfahren die Methode mit der höchsten Sensitivität bei einem gleichzeitig akzeptablen positiven Vorhersagewert. Derzeit nicht endgültig geklärt sind die günstigsten Untersuchungsintervalle und inwieweit der Einsatz aller Verfahren erforderlich ist.

Aromatase expression is increased in BRCA1mutation carriers

BackgroundUntil recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of BRCA1 gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression in vitro. Our objective was to characterise aromatase gene (CYP19A1) and its promoter expression in breast adipose and ovarian tissue in BRCA1 mutation carriers and unaffected controls.MethodsWe measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.ResultsWe demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of BRCA1 mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.ConclusionUnderstanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in BRCA1 mutation carriers.

Age-dependent penetrance of different germline mutations in the BRCA1 gene

Aims:BRCA1 gene mutations have been extensively studied in relation to breast and ovarian cancer susceptibility. Various genotype–phenotype correlation attempts have yielded important data pertaining to the consequences of BRCA1 mutations....

Cost-effectiveness of surgical interventions for BRCA gene mutation carriers: impact of delaying decision-making.

Abstract Abstract #503 Purpose&amp;#x2028; Women who carry a BRCA1 or BRCA2 genetic mutation are at significantly increased risk of breast and ovarian cancer. Interventions to reduce the risk of these cancers available these women include bilateral prophylactic mastectomy (PM) and oophorectomy (PO), or both (PMPO). However, women are often reluctant to choose these options, and prefer to delay these surgeries for childbearing or other reasons. We sought to identify the effectiveness and cost-effectiveness of these interventions and to evaluate the potential consequences of delaying prophylactic surgery in terms of risk of cancer diagnosis and life expectancy.&amp;#x2028; Methods&amp;#x2028; A Markov model was developed to compare the effectiveness and cost-effectiveness of prophylactic surgery in cohorts of women with the BRCA1 and BRCA2 mutations without prior breast or ovarian cancer. Multiple strategies were explored to evaluate the benefit of these interventions at various ages. Costs were estimated using Medicare reimbursement rates and secondary sources. Other model variables were estimated from the literature. Effectiveness was measured in life-years gained and quality-adjusted life-years gained in addition to breast and ovarian cancers diagnosed.&amp;#x2028; Results&amp;#x2028; All surgeries significantly prolong survival at all ages explored (age 30 to 45), although much more so in younger women and in BRCA1 compared to BRCA2 carriers. BRCA1 carriers at age 30 have an increased life expectancy of 4, 8, and 13 years for PM, PO, and PMPO, whereas BRCA2 carriers have an increased life expectancy of 3, 3, and 6 years respectively, vs. 2, 4, 6 years (BRCA1) and 2, 2, 4 years (BRCA2) at age 45. BRCA1 carriers who delay prophylactic surgery are projected to have a 6.4% chance of a cancer diagnosis before age 35 vs. 35% chance before age 45. BRCA2 carriers who delay surgery are projected to have a 2.6% vs. 12.1% chance of cancer diagnosis before age 35 and 45 respectively. Compared to surveillance, all options have incremental cost effectiveness ratios (ICER) less than $50,000 per quality adjusted life year gained in BRCA1 carries. However, some of these strategies are not considered cost-effective in BRCA2 carriers.&amp;#x2028; Conclusions&amp;#x2028; Surgical prophylactic interventions for known BRCA mutation carriers are very effective and cost-effective, although more so in younger women and in BRCA1 carriers as compared to BRCA2 carriers. These interventions are life-saving even when delayed; however, for individuals who have high disutility for prophylactic surgery, these options may reduce quality-adjusted life expectancy regardless of when the surgery is performed. Patients need to be aware of the short-term cancer risk from delaying prophylactic intervention to ensure informed trade-offs. Selection of individuals who perceive low harm or anticipate minimal adjustment to the prophylactic interventions will ensure cost-effective use of these surgical interventions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 503.

LAPAROSCOPIC OOPHORECTOMY IN THE MANAGEMENT OF BREAST DISEASE

Oophorectomy is being increasingly carried out in the management of breast disease, as either adjuvant treatment for breast cancer or for prevention of ovarian and fallopian tube cancer in BRCA gene mutation carriers. The aims of this study were to determine the surgical outcome of laparoscopic oophorectomy when carried out by breast surgeons and whether laparoscopic oophorectomy can be safely carried out during the same anaesthesia as breast surgery. Patients who had laparoscopic oophorectomy carried out by two breast surgeons were reviewed with regard to the indication, surgical outcome and concurrent procedures. Salpingectomy was also carried out when the indication was prevention. Seventy patients with breast disease had laparoscopic oophorectomy between January 2000 and June 2007. Forty-three patients had laparoscopic oophorectomy for adjuvant endocrine treatment of early breast cancer, 13 for prophylaxis, 7 for endocrine and prophylactic reasons and 7 for treatment of metastatic breast cancer. Sixteen patients had laparoscopic oophorectomy and breast surgery at the same time, without complication. Of note, four BRCA mutation carriers had prophylactic mastectomies, bilateral breast reconstruction and bilateral laparoscopic salpingo-oophorectomy. No patient required conversion to an open procedure, including 29 patients with previous abdominal surgery. There were no significant complications. Three patients had ovarian cancer or breast cancer detected in an ovary. Laparoscopic oophorectomy can be safely and efficiently carried out by breast surgeons with expertise in laparoscopic surgery. Previous abdominal surgery did not prevent a successful laparoscopic approach. Breast oncological and/or reconstructive surgery and laparoscopic oophorectomy can be reliably carried out as a combined procedure.

The sensitivity of BRCA1 mutation carriers to ionising radiation: questions of methodology

To the Editor In a recently published paper in your journal, Gronwald et al. [1] set out to establish whether breast cancer risk in BRCA1 gene mutation carriers relates to early chest X-ray exposures. As shown earlier by Andrieu et al. [2], any reported exposure to chest X-rays is associated with an increased risk of breast cancer in BRCA mutation carriers. Gronwald et al. intended to confirm these findings in the Polish population. The researchers assumed that ‘‘women with breast cancer would be more likely to recall or report an early X-ray than women without breast cancer (recall bias)’’; thus, in order to avoid this bias, they decided to examine women with breast cancer but with no BRCA1 mutation as a reference group of better relevance. In other words, the reported number of X-ray exposures was compared in breast cancer patients with and without BRCA1 mutation. Based on this comparison, it was concluded that ‘‘women with a BRCA1 mutation may be more sensitive than non-carriers to the effects of ionising radiation, in terms of breast cancer risk’’. It is a fallacy, and there are no grounds for this conclusion. By comparing BRCA1 mutation carriers with non-carriers, both with breast cancer, one cannot draw any conclusions about the influence of any factor on breast cancer risk in the carriers. The appropriate control group in this study is lacking. The only valid conclusion that might be drawn from this comparative study would be that BRCA1 mutation carriers, for unknown reasons, have had more frequent early age X-ray examination, or that they were more likely to report X-ray exposure, trying (perhaps subconsciously) to explain their weak position as a mutation carrier (recall bias). According to Gronwald et al. there is no reason for the recall bias related to the mutation status. Instead, the researchers discuss the question of a family history of breast cancer, which is in fact a minor issue in this study, as 73% of the affected carriers had no family history of breast cancer. The appropriate conclusive methodological setting for studying the influence of radiation exposure on breast cancer onset in BRCA mutation carriers is that applied by Andrieu et al., i.e. a comparison between BRCA mutation carriers with and without cancer.

The expression of the chosen proteins in ovaries of BRCA1 gene mutation carriers after prophylactic adnexectomy

22191 Among women with BRCA1 mutation the risk of developing breast cancer is 50 - 80%, ovarian cancer 40% and about 10% for Fallopian tube and peritoneal cancer. One of the possibilities to reduce the risk of developing cancer in BRCA1 positive patients is prophylactic adnexectomy. It decreases the risk of ovarian cancer to 5% and breast cancer to 30 - 40%. The aim of our study was to investigate the expression of the TP53, BRCA1, NM23 and KAI1 in the ovaries of the 14 operated women that might be involved in development of breast and ovarian cancer in BRCA1 positive patients. As a control we have studied 11 patients operated at our department which were BRCA1 negative. The determination of TP53, BRCA1, NM23 and KAI1 was performed using immunohistochemistry method. We have observed the differences in the expression of BRCA1, NM23 and KAI1 between study group and control group. The expression of these proteins in the study group were respectively: 78,6%, 71,4%, 92,8% and in control and in the control group: 45%, 36,4% and 63,6%. The expression level of the analysed proteins differs between right and left ovary in BRCA1 carriers. In cases of BRCA1, NM23 and KAI1 the expression was higher in right ovary in case of TP53 the expression was higher in left ovary. No significant financial relationships to disclose.

Breast tumor characteristics of BRCA1 and BRCA2 gene mutation carriers on MRI

The appearance of malignant lesions in BRCA1 and BRCA2 mutation carriers (BRCA-MCs) on mammography and magnetic resonance imaging (MRI) was evaluated. Thus, 29 BRCA-MCs with breast cancer were retrospectively evaluated and the results compared with an age, tumor size and tumor type matched control group of 29 sporadic breast cancer cases. Detection rates on both modalities were evaluated. Tumors were analyzed on morphology, density (mammography), enhancement pattern and kinetics (MRI). Overall detection was significantly better with MRI than with mammography (55/58 vs 44/57, P = 0.021). On mammography, lesions in the BRCA-MC group were significantly more described as rounded (12//19 vs 3/13, P = 0.036) and with sharp margins (9/19 vs 1/13, P = 0.024). On MRI lesions in the BRCA-MC group were significantly more described as rounded (16/27 vs 7/28, P = 0.010), with sharp margins (20/27 vs 7/28, P < 0.001) and with rim enhancement (7/27 vs 1/28, P = 0.025). No significant difference was found for enhancement kinetics (P = 0.667). Malignant lesions in BRCA-MC frequently have morphological characteristics commonly seen in benign lesions, like a rounded shape or sharp margins. This applies for both mammography and MRI. However the possibility of MRI to evaluate the enhancement pattern and kinetics enables the detection of characteristics suggestive for a malignancy.

Sonographic Features of Breast Carcinoma Presenting as Masses in BRCA Gene Mutation Carriers

Sonographic Features of Breast Carcinoma Presenting as Masses in BRCA Gene Mutation Carriers