Basal expression of RAD51 foci predicts olaparib response in patient-derived ovarian cancer xenografts.

BACKGROUND: The search for biomarkers to evaluate ovarian cancer (OC) homologous recombination (HR) function and predict the response to therapy is an urgent clinical need to improve the selection of patients who could benefit from platinum- and olaparib (poly-ADP ribose polymerase inhibitors, PARPi)-based therapies. METHODS: We used a large collection of OC patient-derived xenografts (PDXs) (n = 47) and evaluated their HR status based on BRCA1/2 mutations, BRCA1 promoter methylation and the HRDetect score. RAD51 foci were quantified in formalin-fixed, paraffin-embedded untreated tumour specimens by immunofluorescence and the messenger RNA expression of 21 DNA repair genes by real-time PCR. RESULTS: Tumour HR deficiency predicted both platinum and olaparib responses. The basal level of RAD51 foci evaluated in geminin-positive/replicating cells strongly inversely correlated with olaparib response (p = 0.011); in particular, the lower the foci score, the greater the sensitivity to olaparib, while low RAD51 foci score seems to associate with platinum activity. CONCLUSIONS: The basal RAD51 foci score is a candidate predictive biomarker of olaparib response in OC patients as it can be easily translatable in a clinical setting. Moreover, the findings corroborate the importance of OC-PDXs as a reliable tool to identify and validate biomarkers of response to therapy.

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy.

Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.

PO-44 - Tissue factor pathway inhibitor-2 (TFPI-2) is cleaved by PRSS3: implication for tumor endothelial cells migration.

INTRODUCTION: Tissue Factor Pathway Inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor whose expression is up-regulated by VEGF in microvascular and umbilical vein endothelial cells (EC). Despite this, TFPI-2 has been suggested as anti-angiogenic molecule, due to its ability to inhibit the migration/proliferation of EC induced by VEGF. Nothing is known about the precise mechanism of TFPI-2 function tuning in tumor endothelium. AIM: Aim of this study was to investigate the role of TFPI-2 in tumor vasculature, where angiogenesis and vascular remodeling are fundamental for cancer progression. MATERIALS AND METHODS: Tumor-EC were isolated from ovarian carcinomas and cultured in vitro in presence of factors reproducing the tumor microenvironment (VEGF, FGF-2, EGF). TFPI-2 and PRSS3 silencing was achieved by small interfering RNA (siRNA). Tumor-EC migration was assayed by the wound healing assay. Transcript expression was examined by qRT-PCR. Proteolytic reactions were monitored by western blot. RESULTS: We show that tumor-EC express TFPI-2, the majority of which is released and found anchored in the extracellular matrix. Silencing the expression of TFPI-2 enhances tumor-EC migration, confirming TFPI-2 as an anti-angiogenic molecule. We had previously shown that the cancer vasculature express PRSS3, a trypsin family member able to cleave proteins containing the kunitz-type domains; we reasoned that it could potentially inhibit TFPI-2. Herein, we demonstrate in a cell free system that TFPI-2 directly interacts with and is degraded by active PRSS3. In a more complex biological context, active PRSS3 is able to remove TFPI-2 from the extracellular matrix put down by tumor-EC. Accordingly, silencing PRSS3 causes the extracellular accumulation of TFPI-2 that results in the inhibition of tumor-EC migration. CONCLUSIONS: Our results demonstrate for the first time that TFPI-2 is a direct substrate of PRSS3, which hydrolyses TFPI-2 (most likely at the Kunitz-type domains) blocking its anti migratory capability. The proteolytic inactivation of TFPI-2 by PRSS3 might represent a mechanism favoring cancer by increasing angiogenesis and vascular remodeling. ACKNOWLEDGEMENT: Supported by the Italian Association for Cancer Research (AIRC).

Touch Imprint Cytology and Stereotactically-Guided Core Needle Biopsy of Suspicious Breast Lesions: 15-Year Follow-up.

Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.

Time and Resources Needed to Document Patients with Breast Cancer from Primary Diagnosis to Follow-up - Results of a Single-center Study.

Aim: Certification of breast centers helps improve the quality of care but requires additional resources, particularly for documentation. There are currently no published data on the actual staff costs and financial resources required for such documentation. The aim of this study was to determine the time and resources required to document a patient with primary breast cancer from diagnosis to the end of follow-up, to establish a database for future strategic decisions. Material and Methods: All diagnostic and therapeutic procedures of patients with primary breast cancer were recorded at the University Breast Center of Franconia. All time points for documentation were evaluated using structured interviews. The times required to document a representative number of patients were determined and combined with the staff costs of the different professional groups, to calculate the financial resources required for documentation. Results: A total of 494 time points for documentation were identified. The study also identified 21 departments and 20 different professional groups involved in the documentation. The majority (54 %) of documentation was done by physicians. 62 % of all documentation involved outpatients. The results of different scenarios for the diagnosis, therapy and follow-up of breast cancer patients in a certified breast center showed that the time required for documentation can be as much as 105 hours, costing € 4135. Conclusion: This analysis shows the substantial staffing and financial costs required for documentation in certified centers. A multi-center study will be carried out to compare the costs for certified breast centers of varying sizes with the costs of non-certified care facilities.

Breast Cancer Risk - From Genetics to Molecular Understanding of Pathogenesis.

Several advancements over the last decade have triggered the developments in the field of breast cancer risk research. One of them is the availability of the human genome sequence along with cheap genotyping possibilities. Another is the globalization of research, which has led to the growth of research collaboration into large international consortia that facilitate the pooling of clinical and genotype data of hundreds of thousands of patients and healthy control individuals. This review concerns with the recent developments in breast cancer risk research and focuses on the discovery of new genetic breast cancer risk factors and their meaning in the context of established non-genetic risk factors. Finally the clinical application is highly dependent on the accuracy of breast cancer risk prediction models, not only for all breast cancer patients, but also for molecular subtypes, preferably for those which are associated with an unfavorable prognosis. Recently risk prediction incorporates all possible risk factors, which include epidemiological risk factors, mammographic density and genetic risk factors.

Accuracy of radiological tumour size assessment and the risk for re-excision in a cohort of primary breast cancer patients.

BACKGROUND: Re-operations after breast conserving surgery (BCS) are necessary, when specimen margins are not free of breast cancer cells. This study explored the accuracy of preoperative tumour size assessment and its influence on the rate of re-excisions and mastectomies. METHODS: The study included 1591 patients with invasive breast cancer, who were planned for BCS. Patient, staging and tumor characteristics were evaluated concerning their influence on re-excision and mastectomy rates. Patient and tumor characteristics comprised histopathological tumour size, HER2 status, multifocality, in situ component, grading (G), nodal status and hormone receptor (HR) status. Staging characteristics included deviation from pathological tumour size as measured by clinical examination, sonography and mammography. RESULTS: In 1316 patients (83%) sufficient treatment was possible with one operation. 275 patients (17%) had to undergo at least one further surgery as a result of positive specimen margins. In 138 patients (9%) mastectomy was ultimately necessary. In patients with a positive HER2 status, a larger tumour size, underestimation by ultrasound, an in situ component and multifocality, the risk for a re-operation was about doubled. Tumour size deviation in the mammogram or the clinical tumour size assessment did not have significant influence to the re-excision rates. CONCLUSION: Tumour size and accurate presurgical assessment of the tumour size itself are independent predictors for the need of a second surgery or even a mastectomy in patients for whom a primary BCS was planned.

Expression of the soluble vascular endothelial growth factor receptor-1 in cutaneous melanoma: role in tumour progression.

BACKGROUND: Vascular endothelial growth factor (VEGF)-A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with α5ß1 integrin. OBJECTIVES: To analyse whether sVEGFR-1 plays a role during melanoma progression. METHODS: sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real-time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis. RESULTS: sVEGFR-1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR-1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR-1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the activation of a VEGF-A/VEGFR-2 autocrine loop. CONCLUSIONS: Our data strongly suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR-1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome in patients with melanoma.

Use of Tomosynthesis in Intraoperative Digital Specimen Radiography - Is a Reduction of Breast Re-excision Rates Possible?

Aim: A prospective clinical study was done to see whether it is possible to reduce the rate of re-excisions using digital breast tomosynthesis (DBT) compared commercial FFDM. Material and Method: Between 1/2011 and 5/2011 we diagnosed an invasive breast cancer (BI-RADS 5) in 100 patients. After histological verification we performed breast-conserving therapy with intraoperative imaging using one of 2 different systems: 1. Tomosynthesis (Siemens, Erlangen, Germany), amorphous selenium, Tungsten source, focus 0.1 mm, resolution 85 µm, pixel pitch, 8 l/mm, range: 50°, 25 projections, time for scanning > 20 s, geometry: same scanning scope, reconstruction: filtered back projection; or 2. Inspiration™ (Siemens, Erlangen, Germany), amorphous selenium, tungsten source, focus 0.1 mm, resolution 85 µm, pixel pitch, 8 l/mm as the standard. The 100 radiograms obtained with both systems were prospectively shown on a monitor to 3 radiologists. Results: Out of a total of 100 patients with histologically proven breast cancer (BI-RADS 6) no re-excision was necessary in 78 patients. A retrospective analysis (n = 22) demonstrated an increase in sensitivity of tomosynthesis compared to the Inspiration™ at a magnification of 1.0 : 1.0 of 8 % (p < 0.05), i.e., in 8 patients re-excision would not have been necessary with tomosynthesis. Conclusion: Tomosynthesis has a significant higher sensitivity (p < 0.05) compared with a commercial FFDM system. Studies with higher numbers of patients will be necessary to evaluate this method.

Breast Cancer Risk - Genes, Environment and Clinics.

The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case-control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patient's breast cancer risk.

Health Services Research and Health Economy - Quality Care Training in Gynaecology, with Focus On Gynaecological Oncology.

In the era of cost increases and reduced resources in the German healthcare system, the value of health services research and health economics is increasing more and more. Health services research attempts to develop concepts for the most effective ways to organise, manage, finance and deliver high-quality care and evaluates the implementation of these concepts with regard to daily routine conditions. Goals are the assessment of benefits and the economic advantages and disadvantages of new and established diagnostic methods, drugs and vaccines. Regarding these goals, it is clear that health services research goes hand in hand with health economics, which evaluates the benefits of diagnostic and therapeutic procedures in relation to the costs. Both scientific fields have focus principally on gynaecology and particularly on gynaecological oncology in Germany, as can be seen by numerous publications. These present several advantages compared with clinical trials - they uncover gaps in health care, question the material, staffing and consequently the financial resources required and they allow the estimation of value and the comparison of different innovations to identify the best options for our patients.

The era of centers: the influence of establishing specialized centers on patients' choice of hospital.

PURPOSE: It is considered that establishing accredited specialized centers can serve as a marketing tool. This study investigated whether accredited specialized centers influence patients' choice of hospital. METHODS: A total of 2,389 patients was included in a questionnaire survey: 468 at the Department of Gynecology, 745 at the certified University Breast Center of Franconia, 1,000 at the University Perinatal Center of Franconia and 176 for whom classification details were lacking. RESULTS: Among the oncological patients, physicians in private practice played an important role in the choice of hospital (58.4 vs. 25.7%; P < 0.001; OR 4.058). Among obstetric patients, the primary factors were recommendations from family [odds ratio (OR) 0.495], friends (OR 0.218), and previous personal experience of the hospital (OR 0.695). For oncological patients, treatment quality (OR 2.693), availability of a center (OR 1.785), and certification (OR 3.939) were comparatively more important. For obstetric patients, friendliness (OR 0.409) and attractive accommodation (OR 0.153) were more important. CONCLUSIONS: Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients' choice of hospital.

Factors correlating with reexcision after breast-conserving therapy.

AIM: The aim of this study was to evaluate factors affecting the risk for reexcision following breast-conserving surgery. Positive tumor margins are critical for local disease control following surgery for breast cancer. Several factors, including tumor size, multifocality, and an extensive in situ component, may be associated with a higher rate of repeat operations due to positive margins. This study included mammographic density in the analysis. METHODS: A total of 565 breast cancer patients were considered eligible for breast-conserving therapy after a core biopsy had confirmed malignancy. The patients' mammographic findings were reviewed, and mammographic density was documented in addition to the histopathological features of the lesions. Associations between these factors and the risk for a second operation were analyzed using the chi-squared test, and a model was developed for multivariate analysis. RESULTS: At least one repeat operation was necessary in 121 patients (21.4%), and mastectomy was ultimately necessary in 54 patients (9.6%). Tumor size, multifocality, and the presence of an in situ component were identified as risk factors. A mammographic density of category 4 was associated with a need for further surgery (OR 3.2; 95% CI, 1.2-11). CONCLUSIONS: Mammographic density is an additional risk factor for a second operation following breast-conserving procedures, and it may make radiographic and intraoperative localization of the tumor technically difficult. Using mammographic density to define a group of patients with a higher risk of reexcision might allow these patients to benefit from more sophisticated methods of localization and margin assessment.

Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy.

The aim of this study was to correlate chemotherapy-induced nausea and vomiting (CINV) with commonly occurring single nucleotide polymorphisms (SNP) in the 5-hydroxytryptamine receptor 3 genes (HTR3). Women with breast cancer without previous chemotherapy were eligible for this prospective study. All patients received epirubicin, with or without cyclophosphamide, and preventive medication with ondansetron and dexamethasone. The patients documented every vomiting event on an hourly basis. Real-time polymerase chain reaction (PCR) analysis was performed for the following nonsynonymous SNPs: p.Y129S (HTR3B), p.K163N (HTR3C) and p.A405G (HTR3C). The overall proportion of patients (total n = 110) who reported vomiting in the first 24 h after chemotherapy was 31.8%. The variant genotype of K163N (HTR3C) was associated with vomiting, which occurred in 50.0% (P = 0.009). Polymorphisms in the HTR3C gene could serve as a predictive factor for CINV in patients undergoing moderately emetogenic chemotherapy.

Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer.

PURPOSE: Various ATM (ataxia telangiectasia-mutated) mutations and polymorphisms have been reported to be associated with an increased breast cancer risk. Recent studies have produced contradictory results regarding the association between ATM genetic variants and breast cancer risk. MATERIALS AND METHODS: The common ATM polymorphism 5557G>A (p.D1853N) (rs1801516), previously suggested to be associated with bilateral breast cancer, was analyzed using real-time PCR in 514 unselected patients with breast cancer and 511 age-matched healthy control individuals. DNA was obtained from peripheral blood draw. RESULTS: The ATM genotype was weakly associated with the risk for breast cancer (P = 0.04 for the overall test). The odds ratio for women with a heterozygous genotype was 0.70 (95% CI, 0.52-0.94) and for the homozygous variant 0.63 (95% CI, 0.27-1.49). Disease-free survival and overall survival showed no significant association with specific genotypes. CONCLUSIONS: The results of this study might suggest a minor association between polymorphism 5557G>A and a reduced risk of breast cancer.

Changes in satisfaction in patients with gynaecological and breast malignancies: an analysis with the Socio-Economic Satisfaction and Quality of Life questionnaire.

Quality of life (QOL) is commonly assessed using health-related questionnaires. The Socio-Economic Satisfaction Quality of Life (SES-QOL) questionnaire includes specific individual coping topics, such as health, leisure activities, sexual life, occupation, financial situation, partnership situation, family situation, accommodation situation and friendship situation. This paper reports the findings of the survey with the SES-QOL with an emphasis on changes in satisfaction during the course of a disease involving a gynaecological or breast malignancy. From February 2000 to October 2002, 1030 women diagnosed with breast or gynaecological cancers were included in this study. The patients responded to the SES-QOL questionnaire as part of an interview. Metastatic disease results in more frequent reporting of dissatisfaction with health issues (63%), sexual life (24.5%) and occupation (20%), whereas patients in the adjuvant setting report deteriorating satisfaction with regard to health (41.7%), sexual life (12.2%) and occupation (11.5%). The SES-QOL reflects individual changes in different aspects of satisfaction during the course of a cancer disease. Identifying as many causing variables as possible, and offering support through an interdisciplinary approach including the physician, a social worker and a psycho-oncologist, appears necessary in order to help patients cope with cancer as a dynamic and individual process.

Association of complementary methods with quality of life and life satisfaction in patients with gynecologic and breast malignancies.

GOALS OF WORK: In gynecological oncology, there is growing interest in the use of complementary and alternative medicine (CAM) methods. The lack of data regarding side effects, the lack of any survival advantages, and the costs of these methods appear to have no influence on patients' decisions on whether to use CAM. Our interest was to evaluate the association between CAM use and the patients' quality of life/life satisfaction (QoL/LS). MATERIALS AND METHODS: One thousand thirty women with breast cancer of gynecologic malignancies were asked to participate in this study, which included a questionnaire and a personal interview on CAM. User status was compared with the patient's own description of her QoL/LS and with the cancer type. MAIN RESULTS: CAM was used by 48.7% of all women (n = 502). Breast cancer patients stated that they used CAM in 50.1% and women with gynecological cancer in 44.0%. The use of mistletoe was widespread (77.3%) and was more often seen in breast cancer patients than in gynecological cancer patients (74.4% vs 67.0%). CAM users less frequently stated an overall deterioration of their health status (35.1%) compared to nonusers (50.1%). CAM use resulted in a stated improvement in family conditions (6%) in comparison with the nonusers (2%). CONCLUSIONS: With regard to patients' perception of health status, CAM use is associated with a better coping with their disease. Most other categories of LS are not affected by CAM use. Patient-oriented information comparing standard therapies with CAM methods should be made widely available, and patients' expectations of CAM use should be discussed between the physician and the patient.

Risk and risk assessment for breast cancer: molecular and clinical aspects.

Chemoprevention, prophylactic surgery and intensified screening programs are options which can be offered the patients with an increased lifetime risk (p(life)) for breast cancer (BC). Estimation of p(life) includes BRCA mutation analysis and risk estimation based on individual risk factors and family history. MENDEL and BRCAPRO are models which can estimate mutation carrier status probability (p(mut)), p(life) and p(mut) can be estimated using Cyrillic3 software which incorporates BRCAPRO and MENDEL. To integrate age, hormonal factors and benign breast biopsies in risk assessment the Tyrer-Cuzick model can be used. These models support the decision pro or contra genetic analysis and improve the number of positive gene testing results. Estimations of p(life) and p(mut), based on a mathematical model, should deal with algorithms and penetrance/frequency data adequate to the population counselled. Being the main modulatory factors, reproductive/hormonal data should be incorporated like the Tyrer-Cuzick model does.

[Prophylactic surgery of mammary and ovarian carcinoma]. / Prophylaktische Chirurgie des Mamma- und Ovarialkarzinoms.

New insights into the genetic basis of carcinogenesis have been obtained by modern molecular biological techniques. Several susceptibility genes are known. The hereditary breast and ovarian cancer syndrome (germline mutations in BRCA1 and BRCA2) and endometrial cancer in the context of the hereditary non-polyposis colorectal cancer syndrome (HNPCC), germline mutations in mismatch-repair genes, are the most frequent hereditary cancer syndromes in gynaecology. Mutations in TP53 (Li-Fraumeni syndrome) and PTEN (Cowden's disease), associated with increased risk of breast cancer, are responsible for a smaller portion of familial breast cancer. The risk of inheritance and disease can be identified and defined by investigating family history, risk calculation programs, and genetic testing. Afterwards, options of primary, secondary, and tertiary prevention can be formulated. Presently, prophylactic surgery is the only option proven by clinical trials that can reduce the mortality of hereditary breast and ovarian cancer.