Christine Rappaport

Clinical Practice Guideline for the prevention and early detection of breast and ovarian cancer in women from HBOC (hereditary breast and ovarian cancer) families.

SummaryAn estimated 10 % of breast cancer cases exhibit a higher familial incidence, and functional mutations in BRCA (breast cancer-gene) 1 or 2 are responsible for the development of malignant tumors in approximately half of these cases. Women with a germline mutation in either of the two genes have a lifetime risk of up to 85 % to develop breast cancer, and of up to 60 % risk to develop ovarian cancer. This clinical practice guideline defines the individual and familial tumor constellations that represent an indication for BRCA germline testing. It also describes the therapeutic options (early detection programme vs prophylactic surgery) that arise from the result of a BRCA mutational analysis. This guideline further includes recommendations regarding the use of multigene panels and therapeutic aspects that arise from the selective use of poly ADP ribose polymerase (PARP) inhibitors in patients with known BRCA1 or 2 mutations. It replaces the previous version of the “Clinical Practice Guideline for the Prevention and Early Detection of Breast- and Ovarian Cancer in women from HBOC (hereditary breast and ovarian cancer) families” which was published in 2012.

Leitlinie zur Prävention und Früherkennung von Brust- und Eierstockkrebs bei Hochrisikopatientinnen, insbesondere bei Frauen aus HBOC (Hereditary Breast and Ovarian Cancer) Familien

ZusammenfassungDie vorliegende österreichische Leitlinie zur Prävention und Früherkennung von Brust- und Eierstockkrebs bei Hochrisikopatientinnen – insbesondere bei Frauen aus HBOC-Familien – wurde unter der besonderen Berücksichtigung des aktuellen EUSOMA (European Society of Breast Cancer Specialists) Positionspapiers von oben angeführten Experten gemeinsam erstellt. Die Leitlinie soll die Betreuung von Frauen mit einem erhöhtem Lebenszeitrisiko für Brust- und/oder Eierstockkrebs standardisieren und vereinfachen.SummaryThe Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients—particularly in women from hereditary breast and ovarian cancer families—were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.The Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients--particularly in women from hereditary breast and ovarian cancer families--were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.

[Guideline for the prevention and early detection of breast and ovarian cancer in high risk patients, particularly in women from HBOC (hereditary breast and ovarian cancer) families].

ZusammenfassungDie vorliegende österreichische Leitlinie zur Prävention und Früherkennung von Brust- und Eierstockkrebs bei Hochrisikopatientinnen – insbesondere bei Frauen aus HBOC-Familien – wurde unter der besonderen Berücksichtigung des aktuellen EUSOMA (European Society of Breast Cancer Specialists) Positionspapiers von oben angeführten Experten gemeinsam erstellt. Die Leitlinie soll die Betreuung von Frauen mit einem erhöhtem Lebenszeitrisiko für Brust- und/oder Eierstockkrebs standardisieren und vereinfachen.SummaryThe Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients—particularly in women from hereditary breast and ovarian cancer families—were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.The Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients--particularly in women from hereditary breast and ovarian cancer families--were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.

Treatment of infertility does not increase the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation

OBJECTIVE To evaluate the relationship between use of fertility medication (i.e., selective estrogen receptor [ER] modulator, gonadotropin, or other) or infertility treatment (i.e., IVF or IUI) and the risk of ovarian cancer among women with a BRCA1 or BRCA2 mutation. DESIGN A matched case-control study of 941 pairs of BRCA1 or BRCA2 mutation carriers with and without a diagnosis of ovarian cancer. SETTING Genetic clinics. PATIENT(S) Detailed information regarding treatment of infertility was collected from a routinely administered questionnaire. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals associated with fertility treatment. RESULT(S) There was no significant relationship between the use of any fertility medication or IVF treatment (odds ratio, 0.66; 95% confidence interval 0.18-2.33) and the subsequent risk of ovarian cancer. CONCLUSION(S) Our findings suggest that treatment for infertility does not significantly increase the risk of ovarian cancer among women with a BRCA mutation.

Methyl-binding domain protein-based DNA isolation from human blood serum combines DNA analyses and serum-autoantibody testing

BackgroundCirculating cell free DNA in serum as well as serum-autoantibodies and the serum proteome have great potential to contribute to early cancer diagnostics via non invasive blood tests. However, most DNA preparation protocols destroy the protein fraction and therefore do not allow subsequent protein analyses. In this study a novel approach based on methyl binding domain protein (MBD) is described to overcome the technical difficulties of combining DNA and protein analysis out of one single serum sample.MethodsSerum or plasma samples from 98 control individuals and 54 breast cancer patients were evaluated upon silica membrane- or MBD affinity-based DNA isolation via qPCR targeting potential DNA methylation markers as well as by protein-microarrays for tumor-autoantibody testing.ResultsIn control individuals, an average DNA level of 22.8 ± 25.7 ng/ml was detected applying the silica membrane based protocol and 8.5 ± 7.5 ng/ml using the MBD-approach, both values strongly dependent on the serum sample preparation methods used. In contrast to malignant and benign tumor serum samples, cell free DNA concentrations were significantly elevated in sera of metastasizing breast cancer patients. Technical evaluation revealed that serum upon MBD-based DNA isolation is suitable for protein-array analyses when data are consistent to untreated serum samples.ConclusionMBD affinity purification allows DNA isolations under native conditions retaining the protein function, thus for example enabling combined analyses of DNA methylation and autoantigene-profiles from the same serum sample and thereby improving minimal invasive diagnostics.

Clinical implications of genetic testing for BRCA1 and BRCA2 mutations in Austria

The objective of this study was to describe the experience of genetic testing in Austrian women with a BRCA1 or BRCA2 mutation in terms of preventive measures taken and incident cancers diagnosed. We collected clinical information on 246 Austrian women with a BRCA1 or BRCA2 mutation tested between 1995 and 2012 and followed 182 of them for an average of 6.5 years. Of the 90 women who were cancer‐free at baseline, 21.4% underwent preventive bilateral mastectomy, 46.1% had preventive bilateral salpingo‐oophorectomy, and 1 took tamoxifen; 58.8% of the at‐risk women underwent at least one screening breast magnetic resonance imaging (MRI). Of the 85 women with breast cancer, 69.4% had a unilateral mastectomy or lumpectomy and 30.6% had a contralateral mastectomy. In the follow‐up period, 14 new invasive breast cancers (6 first primary and 8 contralateral), 1 ductal carcinoma in situ case, 2 incident ovarian cancer cases, and 1 peritoneal cancer were diagnosed. In Austria, the majority of healthy women with a BRCA1 or BRCA2 mutation opt for preventive oophorectomy and MRI screening to manage their breast cancer risk; few have preventive mastectomy or take tamoxifen.

Impact of lifestyle factors on preneoplastic changes in prophylactic oophorectomies of BRCA mutation carriers

BRCA mutation carriers are at high risk of developing ovarian cancer. Ovarian malignancies are usually identified at an advanced stage with poor prognosis, attributed to inadequate options of early detection. Because of its risk-reducing effect of nearly 96%, prophylactic salpingo-oophorectomy is still the leading option for risk-reduction in women with a positive BRCA mutation status. The presence of ovarian cancer precursor lesions, such as epithelial inclusion cysts (EICs) or cortical invaginations (CIs), has previously been discussed in several studies with diverse conclusions. We retrospectively investigated a large and consistent population (n=94) of BRCA mutation carriers for the presence of potential preneoplastic and neoplastic changes. We also examined the role of specific lifestyle factors. Ninety-four women with disease-associated germline BRCA1 or BRCA2 mutations were included in this retrospective study. All women had undergone genetic counseling and prophylactic salpingo-oophorectomy, which was performed at a mean age of 43.33 years (range 27–66). Histological slides of both ovaries were reviewed by an independent pathologist. Data concerning lifestyle factors were collected from medical files and questionnaires. Two malignant lesions (2.1%), one bilateral serous papillary adenocarcinoma of the epithelial surface and one adenocarcinoma of the peritoneum with involvement of the left adnexa, and one lesion (1.1%) with obvious malignant potential, one mucinous borderline tumor of the right ovary, have been identified. We registered a high prevalence of CIs (30; 31.9%) and EICs (44; 46.8%) in prophylactically removed ovaries of BRCA mutation carriers. A significant correlation (P=0.002) was found with regard to the presence of EICs in women with increased BMI. Concerning the regular consumption of alcohol as a risk factor for premalignant lesions, in particular CIs, a statistically insignificant trend (P=0.083) was noted. Overweight women seem to be at risk of developing more cortical invaginations than women of normal weight. To improve the final outcome of the disease, women at increased risk of ovarian cancer should be appropriately informed of potential increased risk factors.

Identification and management of familial breast cancer in Austria

Abstract Aim The aim of this study is to review the legal implications, the technology, the indications and the management of women with a familial background of breast and/or ovarian cancer. Methods We have reviewed the literature and national Austrian guidelines to describe the uptake of genetic counseling and the management options offered in Austria. Results Genetic testing for the BRCA1 and 2 mutations is free and readily available through a nation-wide program. Increased awareness and the availability of screening programs and prophylactic surgery have resulted in a profound increase in genetic counseling and testing in women with a familial background of breast and ovarian cancer in Austria. Conclusion While readily available country-wide counseling has led to an increase in counseling and testing, Austrian legislation mandates “non-directional counseling” resulting in a comparatively low uptake of prophylactic surgery.

Leitlinie zur Prävention und Früherkennung von Brust- und Eierstockkrebs bei Hochrisikopatientinnen, insbesondere bei Frauen aus HBOC (Hereditary Breast and Ovarian Cancer) Familien@@@Guideline for the prevention and early detection of breast and ovarian cancer in high risk patients, particularly in women from HBOC (hereditary breast and ovarian cancer) families

ZusammenfassungDie vorliegende österreichische Leitlinie zur Prävention und Früherkennung von Brust- und Eierstockkrebs bei Hochrisikopatientinnen – insbesondere bei Frauen aus HBOC-Familien – wurde unter der besonderen Berücksichtigung des aktuellen EUSOMA (European Society of Breast Cancer Specialists) Positionspapiers von oben angeführten Experten gemeinsam erstellt. Die Leitlinie soll die Betreuung von Frauen mit einem erhöhtem Lebenszeitrisiko für Brust- und/oder Eierstockkrebs standardisieren und vereinfachen.SummaryThe Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients—particularly in women from hereditary breast and ovarian cancer families—were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.The Austrian guideline for prevention and early detection of breast and ovarian cancer in high risk patients--particularly in women from hereditary breast and ovarian cancer families--were established with particular consideration of the most recent position paper of the European Society of Breast Cancer Specialists (EUSOMA) by the authors mentioned above. The guideline is aimed at facilitating and standardizing the care and early detection strategies in women with an elevated life time risk for breast and ovarian cancer.