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Ovarian cancer typically presents at advanced stage with intra-abdominal metastases. Rarely, ovarian cancer presents with distant metastases with little to no intra-abdominal disease burden. The patient was a BRCA-2 germline mutation carrier diagnosed with a Stage IVB high-grade carcinoma of the fallopian tube following discovery of a right axillary breast mass on screening mammography. Pre-operative imaging was without evidence of metastatic disease in the abdomen or pelvis. She underwent surgical staging followed by adjuvant chemotherapy and maintenance poly-ADP ribose polymerase (PARP) inhibition. She is without evidence of disease 24 months following her surgical staging procedure. An isolated oligo metastasis in the axilla is a rare presentation of ovarian carcinoma. Extra-abdominal metastases can present a diagnostic challenge in ovarian cancer necessitating thorough pathologic and radiologic work-up, particularly in the absence of intra-abdominal disease.

Introduction: In prostate cancer , there has recently been an emerging interest in mutations in genes belonging to the homologous recombination repair (HRR) pathway and in the inhibition of poly (ADP-ribose) polymerase (PARP) proteins.Areas Covered: Mutations in the HRR genes, including BRCA1, BRCA2, and Ataxia-Telangiesctasia mutated (ATM), have been reported in prostate cancer, with different incidence in the localized and advanced settings. The PARP enzyme complex is involved in repair of DNA damage and its inhibition causes the accumulation of DNA mutations in HRR deficient cells. Several PARP inhibitors (PARPi) are under development, such as olaparib, talazoparib, niraparib, rucaparib, and veliparib. In metastatic castration resistant prostate cancer (mCRPC), olaparib has been the most studied and its clinical efficacy has been validated in a phase III clinical trial. Rucaparib and niraparib have also shown promising results in the preliminary analyzes of two phase II trials, while talazoparib is currently under development.Expert Opinion: PARPi have become part of the treatment of mCRPC. Early results of combination therapy with PARPi and new hormonal therapy are promising and are supported by a strong biological rationale. Current results need to be validated in randomized phase III-controlled trials in order to translate the use of PARPi into real world practice. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is the most common cancer in women and the most common cause of death. Many tumor suppressor genes, oncogenes and DNA repair genes play a role in breast cancer formation. Tumor suppressor genes are genes known to cause breast cancer of p53, ATM, PTEN, BRCA-1 and BRCA-2 genes. In our country, there is a need for studies on mutation detection in BRCA-1-2 genes. In this study, the frequency of polymorphism mutations in BRCA-1-2 genes in other regions of our country was investigated in our region. In our study, young age group (under the age of 44) in the Department of Oncology at Dicle University was studied from the tumor tissues of 96 patients who were diagnosed with breast cancer in women. We aimed to determine the polymorphic mutations of BRCA-1 (rs16942, rs1799966) and BRCA-2 (rs144848, rs1799944) genes using the "LightCycler" PCR instrument from PCR specific detection group by Hybridization Probe Method. Results: 14 (14.5%) homozygotes (GG) and 55 (57.3%) heterozygotes (AG) were found in rs16942 of the BRCA-1 gene of the study patients; 18 (18.7%) homozygotes (GG) and 46 (47.9%) heterozygotes (AG) in rs1799966; 9 (9.37%) homozygotes (TT) and 25 (26.04%) heterozygotes (GT) in the BRCA-2 gene rs144848; We found polymorphic gene mutations in 2 (2.08%) homozygous (GG) and 3 (3.12%) heterozygous (AG) patients in rs1799944. We found that these mutations were not associated with stage, ER positivity, Grade, age and HER-2 positivity. Age and mutation frequency increased at age 35 but p value was not significant. When the stage and mutation frequency were examined, the rate of stage 2 and stage 3 mutations increased and p value was not clinically significant. Similarly, when we look at the relationship between grade and mutation rate, we found that the frequency of grade 2 and grade 3 mutation was higher but not clinically significant. Conclusion: These polymorphism mutations were found to be important in terms of our region. For this reason, it is necessary to carry out genetic screening of breast cancer cases and family members at early ages. We also found that these polymorphism mutations in BRCA-1 / BRCA-2 were not associated with age, stage, grade, ER status, HER status. [ABSTRACT FROM AUTHOR]

A numerical illustration of a hybrid design and numerical analysis of graphene-coated fiber-optic surface plasmon resonance (SPR) biosensor for BRCA-1 and BRCA-2 genetic breast cancer detection is provided. Two specific mutations named 916delTT in BRCA-1 gene and 6174delT in BRCA-2 gene are being selected for detection of breast cancer numerically. This sensor is based on attenuated total reflection (ATR) method to detect individual point mutations in BRCA-1 and BRCA-2 genes. Based on the numerically obtained results, a momentous change is present in the SPR angle (minimum 35% more) and surface resonance frequency (SRF) (minimum 36% more) for probe DNA with various concentrations of target DNA corresponding to the mutation of the BRCA-1 and BRCA-2 genes. The variation of the SPR angle and SRF for mismatched DNA strands in BRCA-1 and BRCA-2 genes is quite negligible, whereas that for complementary DNA strands is considerable. This considerable change is essential for proper detection of genetic biomarkers (916delTT and 6174delT) for early breast cancer. To the best of our knowledge, this is the first demonstration of such an adept biosensor for detecting BRCA1 and BRCA2 genetic breast cancer. Here, we used graphene as bimolecular acknowledgement element for improving sensor performance. At the end of the article, the performance in terms of sensitivity is analyzed. Therefore, the proposed biosensor opens a window toward detection of early detection of BRCA-1 and BRCA-2 genetic breast cancers. [ABSTRACT FROM AUTHOR]

The recent discovery of the BRCA-1 and BRCA-2 genes as contributing factors to hereditary breast cancer has significantly improved our understanding of familial breast cancer. Deleterious mutations in both BRCA-1 and BRCA-2 in an individual patient is exceedingly rare, with few case reports in the literature, particularly among non-Caucasian, non-Jewish families. We describe here two cases of deleterious mutations in both genes in a cohort of Korean women with early onset breast cancer. [ABSTRACT FROM AUTHOR]

With the current understanding of sporadic and familial breast cancer, it is now possible to identify individuals who have a moderate or high risk of breast cancer. For these individuals, it is useful to perform formal cancer risk assessment and develop an individualized risk reduction plan, including a tailored plan for cancer screening, preventive therapy, and/or prophylactic surgery. Assessment using a predictive model such as the Gail model is particularly useful in individuals at increased risk for sporadic breast cancer. In addition, assessment of risk based on histologic appearance of benign or premalignant breast lesions can be used to identify individuals for whom more aggressive risk reduction strategies are warranted. For individuals who are at risk for familial cancer syndromes, other predictive models are more appropriate. For this extremely high-risk group, genetic testing for mutations in familial cancer susceptibility genes is helpful to identify individuals who would benefit from even more aggressive cancer risk reduction strategies. Strategies to identify the levels of risk for breast cancer, including the identification of moderate, high, or very high risk groups are discussed. Management options for these groups are presented, including who to consider for more aggressive screening, chemoprevention, or prophylactic surgery. Current recommendations for screening, chemoprevention, and surgery for each risk group are presented. The ability to identify individuals at high risk for breast cancer now enables clinicians to intervene to reduce the risk of breast cancer. Aggressive screening, preventive therapy, and prophylactic surgery in moderate- to high-risk individuals should, in the future, significantly reduce the incidence of invasive breast cancer. [ABSTRACT FROM AUTHOR]

Despite an abundance of information available for dealing with patients withBRCA-1andBRCA-2mutations, little guidance is available to assist the surgeon in dealing with the genetically high-risk patient recently diagnosed with breast cancer. A retrospective review was undertaken of 170 patients who underwent genetic counseling and testing over a 3-year period from March 2000 to March 2003. Forty-three of the 170 patients tested were diagnosed with breast cancer prior to genetic testing. Nine patients (20.9%) tested positive for a deleterious mutation. Fifty-eight percent underwent genetic counseling prior to definitive cancer surgery. Five of the 25 patients who underwent lumpectomy tested positive for a deleterious mutation. Testing results became available during systemic therapy or radiation was delayed until results were known. After counseling, all five patients testing positive went on to bilateral prophylactic mastectomy and reconstruction. None had radiation therapy. Because of a strong family history, eight patients elected to undergo prophylactic mastectomy and reconstruction prior to obtaining genetic test results; and despite compelling histories, all eight tested negative for a mutation. Treatment algorithms are developed to manage patients that are first discovered to be at high risk for aBRCA-1orBRCA-2mutation at the time they are diagnosed with breast cancer. Patients diagnosed with breast cancer who are discovered to be at high risk for a genetic mutation should undergo counseling prior to definitive surgery. This maximizes the time that patients have to consider options for prophylaxis and monitoring should their test be positive. It also prevents women who would otherwise be candidates for breast preservation from undergoing unnecessary radiation therapy should they chose prophylactic mastectomy in the face of a positive test. [ABSTRACT FROM AUTHOR]

Recently cancer susceptibility syndromes have been characterized that suggest possible genetic linkages between breast cancer and prostate cancer within families. Despite these connections, male breast cancer and prostate cancer in an individual man has rarely been reported. The clinical features of 10 patients with both of these cancers are described here. One hundred sixty-one patients with male breast cancer were seen at the Dana-Farber Cancer Institute and Massachusetts General Hospital between 1977 and 2000. Of these, 10 were identified who also had prostate cancer. A retrospective review of records from these 10 patients was performed. Breast cancer preceded prostate cancer in eight of these men. The mean age of diagnosis of breast cancer was 65.7 years (range 47–72 years). Twenty percent had nodal involvement at diagnosis and two patients ultimately developed evidence of metastatic disease. The mean age of diagnosis of prostate cancer was 68.0 years (range 51–76 years) with a median prostate-specific antigen (PSA) level at diagnosis of 6 ng/ml (range 1.8–47.5 ng/ml). Seven patients had a family history of female breast cancer in a first-degree relative, while one had a family history of prostate cancer. At a median follow-up of 6.5 years from initial cancer diagnosis, one patient had died of metastatic breast cancer and another had died of metastatic prostate cancer. The clinical features and course of the breast cancers diagnosed in this series do not appear significantly different from those described for the general population of male breast cancer patients. In addition, these men do not appear to develop prostate cancer at an earlier age or more aggressive stage than the general population. [ABSTRACT FROM AUTHOR]

Women at high risk of hereditary breast and/or ovarian cancer require specific management strategies for cancer prevention and early detection. The goal of this study was to determine the prevalence of familial breast and ovarian cancer among patients in a primary care practice. Questionnaires were mailed to the 608 women less than 81 years of age in a single primary care practice. Additional mailings and phone calls were used for nonresponders. Data were analyzed by bloodline, the degree of relative, age of diagnosis and cancer type. Women were grouped into three categories of breast/ovarian family history: “no family history,”“insignificant family history,” and “significant potentially high-risk family history” (women with two or more relatives in a single bloodline with breast and/or ovarian cancer, a single individual with bilateral breast cancer or breast and ovarian cancer, or breast and/or ovarian cancer at less than 40 years of age). A pedigree analysis of women categorized as “significant potentially high-risk family history” further classified these women as to the likelihood of being at risk for hereditary cancer. Data were obtained from 567 women (93%); 27 patients with a personal diagnosis of breast and/or ovarian cancer were excluded. Of the 540 remaining respondents, 351 (65%) had no family history of cancer, 138 (25.6%) had an insignificant family history, and 51 (9.4%) had a significant family history. Based on pedigree analysis of these 51 patients, 19 were unlikely to be at high risk for hereditary cancer, and 32 (6%) were likely to be at significant risk and warrant intensive evaluation. The large proportion of women identified with a significant family history of breast and/or ovarian cancer has major implications regarding the magnitude of a population-based process to identify and manage high-risk individuals. [ABSTRACT FROM AUTHOR]

Breast cancer in men is a rare cancer manifestation, accounting for less then 1% of all breast cancers in both genders. The incidence in Germany during the last years has been approximately 1.0 per year/100,000. In the US, only 0.2% of all malignancies in men. Predisposing risk factors seem to include radiation exposure, hereditary factors, estrogen administration, and diseases associated with hyperestrogenism, such as cirrhosis of the liver or genetic syndromes (i.e. Klinefelter disease). The incidence of male breast cancer is increased in families with a number of first degree relatives affected with breast or prostate cancer. An increased risk of male breast cancer has been reported in families with a mutation of the breast cancer susceptibility gene BRCA-2. For a period of decades, prognosis of breast cancer in males was thought to be worse than that of female patients. Data and cases being published demonstrate that prognosis and strategies of treatment in male breast cancer do not differ from those in females. The cases presented clearly demonstrate that diagnostic work-up, staging procedures and treatment options for primary treatment and advanced stages are identical compared to the recommendation for female breast cancer. [Copyright &y& Elsevier]

Abstract: Background.: Recently, a high incidence of BRCA1 cancer predisposing mutation was described among patients with Uterine Serous Papillary Carcinoma (USPC). A BRCA2 germline mutation in a USPC patient has never been reported. Case.: A 65-year-old Ashkenazi Jewish woman was diagnosed with USPC Stage III A. The patient family history included a mother with ovarian carcinoma, a maternal aunt who had breast carcinoma that was diagnosed at an early age, an additional maternal aunt who suffered from gastric carcinoma, and the patient''s sister who had duodenal carcinoma. The patient was found to be a carrier of the germline BRCA2 cancer predisposing mutation (6174delT). Conclusions.: We report the first case of a BRCA2 mutation in a USPC patient. A strong family history of breast and ovarian cancer with the presence of the BRCA2 germline mutation is an additional hint for the possible association between BRCA cancer predisposing mutations and USPC. [Copyright &y& Elsevier]