Search

Cutaneous T-cell lymphomas are very rare in children. Although mycosis fungoides is the most common of these rare cutaneous T-cell lymphomas in children, transformation to an aggressive malignancy remains extremely uncommon, and there are no clear guidelines for clinical management in the pediatric population. In addition, the increased usage of next-generation sequencing for pediatric patients with unusual malignancies may result in the discovery of pathogenic germline mutations, though the association between these mutations and the patient's cancer is not always clear. We present here a unique pediatric case of transformed mycosis fungoides in a patient with BRCA2 mutation.

Background: Patients with a BRCA1 or BRCA2 mutation (BRCA-mutated breast cancer) are frequently diagnosed with low differentiated and highly proliferating breast cancer characterized by high amounts of tumor-infiltrating lymphocytes (Tils). Stromal Tils (sTils) are highly prognostic in sporadic triple-negative and HER2 positive breast cancer however, their prognostic importance in BRCA-mutated breast cancers is unknown. Material and methods: Formalin-fixed paraffin-embedded primary tumor tissue from 411 patients with a germline BRCA1 or BRCA2 mutation and diagnosed with early breast cancer was included. The percentage of sTils was quantified on full HE sections according to guidelines proposed by the Immuno-Oncology Biomarker in Breast Cancer Working Group. Distribution of sTils and associates with patient and tumor characteristics were assessed according to categorical sTils groups defined as low (

The greater availability and use of genetic testing have improved our ability to determine that men with BRCA2 mutations are at significantly higher risk of developing and dying of prostate cancer. We should continue research efforts in secondary prevention for this population, but must also explore primary preventative strategies such as prophylactic prostatectomy. Efforts are under way at our institution for a clinical trial in this area.

BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation.METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features.RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56).CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

Background Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with BRCA mutations and measured choices and sequence of breast cancer risk reduction strategies. Methods Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women’s recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices. Results Among 598 respondents, mean age was 40.9 years (range 25–55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen. Conclusions Women revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with BRCA1 or BRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a malignant small round cell sarcoma commonly occurring among children, adolescents, and adults. We report a rare case of ES/pPNET arising from the lung in a 49-year-old woman. She was found to have a mass in the right lung on a screening imaging study for her BRCA2 mutation. A lobectomy was performed and the mass had histological, immunohistochemical, and molecular features of ES/pPNET. Few cases of primary pulmonary Ewing sarcoma have been reported.

BACKGROUND Female carriers of BRCA1 or BRCA2 germline mutations are at a substantially increased risk for developing breast and ovarian cancer. The lack of effective early detection schemes for ovarian cancer, mandate surgical removal of adnexa at age 35-40 years in these high-risk women. The role of circulating cell-free DNA (cfDNA) levels as a marker for early detection in high-risk women has rarely been reported. OBJECTIVE To quantify cfDNA levels in BRCA1BRCA2 carriers. METHODS Serum cfDNA levels, measured by direct fluorometric assay in cancer-free female BRCA1BRCA2 mutation carriers were compared with cancer-free controls recruited from among women undergoing breast biopsy or routine colonoscopy. RESULTS Overall, 10 BRCA1 (185delAG) and 10 BRCA2 (6174delT) mutation carriers, 20 breast biopsy controls, and 20 colonoscopy controls participated. cfDNA levels [Median (95% CI)], were 472 (317-589) ng/ml and 525 (339-621) ng/ml in breast biopsy and colonoscopy controls, respectively. Median levels of cfDNA in BRCA1 and BRCA2 mutation carriers combined were 921 (835-1087) ng/ml, significantly higher than in both controls (P< 0.0001). CONCLUSIONS cfDNA levels are significantly higher in BRCA1 and BRCA2 mutation carriers compared with non-carriers. This finding, if validated, may facilitate development of early detection breast/ovarian cancer biomarker in high-risk women.

Purpose BRCA2 mutation carriers are offered annual breast screening with MRI and mammography. The aim of this study was to investigate the supplemental value of mammographic screening over MRI screening alone. Methods In this multicenter study, proven BRCA2 mutation carriers, who developed breast cancer during screening using both digital mammography and state-of-art breast MRI, were identified. Clinical data were reviewed to classify cases in screen-detected and interval cancers. Imaging was reviewed to assess the diagnostic value of mammography and MRI, using the Breast Imaging and Data System (BI-RADS) classification allocated at the time of diagnosis. Results From January 2003 till March 2019, 62 invasive breast cancers and 23 ductal carcinomas in situ were diagnosed in 83 BRCA2 mutation carriers under surveillance. Overall screening sensitivity was 95.2% (81/85). Four interval cancers occurred (4.7% (4/85)). MRI detected 73 of 85 breast cancers (sensitivity 85.8%) and 42 mammography (sensitivity 49.9%) (p Eight mammography-only lesions occurred. In 1 of 17 women younger than 40 years, a 6-mm grade 3 DCIS, retrospectively visible on MRI, was detected with mammography only in a 38-year-old woman. The other 7 mammography-only breast cancers were diagnosed in women aged 50 years and older, increasing sensitivity in this subgroup from 79.5% (35/44) to 95.5% (42/44) (p ≤ 0.001). Conclusions In BRCA2 mutation carriers younger than 40 years, the benefit of mammographic screening over MRI was very small. In carriers of 50 years and older, mammographic screening contributed significantly. Hence, we propose to postpone mammographic screening in BRCA2 mutation carriers to at least age 40.

The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause. A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women. There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar. We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO. The BCFR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organisations imply endorsement by the US Government or the BCFR. CNIO was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare Diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program-grant #CRN-87521-and the Ministry of Economic Development, Innovation and Export Trade-grant #PSR-SIIRI-701. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministere de l'Economie, de la Science et de l' Innovation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. Jacques Simard is a Chairholder of the Canada Research Chair in Oncogenetics. EMBRACE is supported by the Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by an NIHR grant to the Biomedical Research Centre, Manchester (IS-BRC-1215-20007). The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by the Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007-2013)/European Research Council (310018). The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, no. 2014-008). HCSC was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054. The IHCC was supported by Grant PBZ_ KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the National Institute of Health U.S.A. (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation fellow. MODSQUAD-Czech Republic, Brno, was supported by MH CZ -DRO (MMCI, 00209805) and by MEYS -NPS I -LO1413 to LF and MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228, and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. The funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication. Sí

Leptomeningeal carcinomatosis (LC) is a devastating complication of metastatic cancer that disproportionately affects patients with advanced breast cancer. Moreover, those with BRCA1/2-mutated disease more often experience leptomeningeal metastasis. Treatment options for LC are limited and often include significant toxicities. PARP inhibitors offer an important potential treatment for patients with BRCA1/2-mutated breast and ovarian cancers, but clinical studies excluded patients with central nervous system (CNS) metastases, including LC. Efficacy data in this area are therefore limited, although a phase I study of olaparib in glioblastoma did show CNS penetration. Here we report a case of a patient with BRCA2-mutated breast cancer and solitary recurrence in the leptomeninges with ongoing complete response to treatment with the PARP inhibitor olaparib. PARP inhibitors may be an important treatment option for patients with BRCA-mutated disease and LC, and warrant further study.

Introduction/Background BRCA 1 and 2 mutated women have a 40–85% lifetime risk of developing breast cancer (BC) and 16–64% risk of ovarian cancer (OC). Literature data evaluating the role of pregnancies on risk of BC and OC in BRCA mutated patients are controversial. The objective of the present study is to evaluate the impact of pregnancy on cancer risk in a cohort of BRCA1/2 mutated patients. Methodology This is a retrospective study, conducted on a sample of 106 female patients, 83 (78%) with BRCA 1 mutation and 23 (22%) BRCA 2, involved in a follow-up program of two different divisions of the University of Cagliari. We evaluated the number of BC and OC and the age of cancer diagnosis correlating to the number of pregnancies. Results Of 106 patients, 39 (36,8%) patients did´t have diagnosis of cancer and 67 (63,2%) developed cancer: 48 BC, 12 OC and 7 both. Thirthy-nine (36,8%) women didn´t have pregnancy, 21 (19,8%) had one pregnancy, 27 (25,4%) had two pregnancies and 19 (17,9%) more than two pregnancies. The median age at the cancer diagnosis was 43,3 years (range 19–69 years). We found a significative difference on the age of cancer diagnosis in patients with two or more pregnancies (p-value Conclusion Our results seems to suggest a protective effect of pregnancy on the development of cancer in BRCA mutated women. Data show that two or more pregnancies significantly delay the development breast and ovarian cancer. Disclosure Nothing to disclose.

Key Clinical Message We used a multi‐gene panel testing to identify the germline variants in a mother‐daughter pair with early‐onset breast cancer, and detected one pathogenic protein‐truncating variant in BRCA2. Our results highlight the importance of genetic testing in identifying the pathogenic mutation running in cancer families.

Introduction. Patients with sporadic breast cancer (BC) have low contralateral breast cancer risk (CLBCR; approximately 0.7% per annum) and contralateral pro- phylactic mastectomy (CPM) offers no survival advantage. CPM with autologous reconstruction (AR) has major morbidity and resource implications. Objective. The aim of this study was to review the impact of PREDICT survival estimates and lifetime CLBCR scores on decision making for CPM in patients with uni- lateral BC. Methods. Of n = 272 consecutive patients undergoing mastectomy and AR, 252 were included. Five- and 10-year survival was computed with the PREDICT(V2) online prognostication tool, using age and clinicopathological factors. Based on family history (FH) and tumor biology, CLBCR was calculated using validated BODICEA web- based software. Survival scores were correlated against CLBCR estimates to identify patients receiving CPM with ‘low’ CLBCR ( \ 30% lifetime risk) and poor prognosis (5- year survival \ 80%). Patients with ‘high’ CLBCR receiving unilateral mastectomy (UM) were similarly identified (UK National Institute of Health and Care Excellence [NICE] criteria for CPM, C 30% lifetime BC risk). Justifications motivating CPM were investigated. Results. Of 252 patients, 215 had UM and 37 had bilateral mastectomy and AR. Only 23 (62%) patients receiving CPM fulfilled the NICE criteria. Of 215 patients, 5 (2.3%) failed to undergo CPM despite high CLBCR and good prognosis. CPMs were performed, at the patient’s request, for no clear justification ( n = 8), contralateral non-invasive disease, and/or FH ( n = 5), FH alone ( n = 4) and ipsilateral cancer recurrence-related anxiety ( n = 3). Conclusion. In the absence of prospective risk estimates of CLBCR and prognosis, certain patients receive CPM and reconstruction despite modest CLBCR, yet a propor- tion of patients with good prognoses and substantial risk are not undergoing CPM

Breast cancer is the second leading cause of cancer-related deaths in women in the United States. Of these women, 5–10% have an inherited form of breast cancer with a mutation in a major gene, such as the breast cancer susceptibility genes 1 or 2 (BRCA1 or BRCA2). Triple negative (the most common subtype of BRCA1-associated breast cancers) and Her2-positive breast cancer patients have more frequently been observed to develop central nervous system (CNS) metastases compared to other molecular subtypes of breast cancers. However, it remains an open question if BRCA2-associated breast cancers also have a higher propensity to develop CNS metastases. Here we report a rare case of recurrent BRCA2-associated breast cancer which manifested as orbital metastases. At the time of this publication, this is one of the first cases of BRCA2-associated breast cancer to present with orbital metastases. In this article, we discuss the diagnostic challenges and review the literature regarding this rare presentation.

The efficiency of a novel targeted next-generation sequencing (NGS) test, the Devyser BRCA kit, for a comprehensive analysis of all 48 coding exons of the high-risk breast/ovarian cancer susceptibility genes BRCA1 and BRCA2 has been assessed. The new assay intended to detect nucleotide substitutions, small deletions/insertions, and large deletions/duplications. To document the false-negative and false-positive rates of the NGS assay in the hands of end users, 48 samples with previously identified 444 small variants and seven gross rearrangements were analyzed, showing 100% concordance with gold standards. Furthermore, all other 43 variants (42 single-nucleotide variation or insertion/deletion variation and one copy number variation, whose significance is or may be of clinical value), which were called by the NGS assay in a prospectively analyzed 179-sample set, were confirmed by Sanger sequencing or multiplex ligation probe amplification, according to their nature. We conclude that the Devyser BRCA kit performed satisfactorily for use in a clinical laboratory.

Ovarian remnant syndrome (ORS), in which a portion of the ovary is retained following bilateral salpingo-oophorectomy (BSO), is uncommon but can negatively impact patient management. Evaluation should be performed in a patient who has clinical signs or symptoms suggestive of ORS, especially in a premenopausal woman with breast cancer who is treated with an aromatase inhibitor following bilateral salpingo-oophorectomy (BSO), or a woman with a pathogenic variant in BRCA1 or BRCA2 who undergoes BSO for ovarian cancer risk reduction.

This case report presents a 38-year-old female who was scheduled for abdominal panniculectomy and tested positive for BRCA2 mutation through Geisinger MyCode®. She canceled her panniculectomy and elected to proceed with bilateral mastectomies, utilizing her abdominal tissue for deep inferior epigastric perforator flap reconstruction.

In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood.We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy.In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy.We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P.001).Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.

Purpose We sought to determine to what extent the knowledge of carrying a BRCA1 or BRCA2 mutation influences the uptake of preventive surgeries in Bahamian women, including bilateral salpingo‐oophorectomy and bilateral mastectomy. Patients and methods The study population consisted of 78 female residents of the Bahamas for whom a BRCA1 or BRCA2 mutation had been detected between 2004 and 2014. The mean age of the 78 participants at the time of genetic testing was 46 years (age range 22–73 years). The mean time of follow‐up was 4.4 years. Results Of the 78 study participants, 19 women had a bilateral salpingo‐oophorectomy (24%). Seven out of 37 patients who had unilateral breast cancer chose to remove the unaffected contralateral breast (19%). Three of 13 patients with no history of breast cancer chose to have a prophylactic bilateral mastectomy (23%). Conclusion Preventive surgery is an acceptable option for a significant proportion of Bahamian women with a BRCA1 or BRCA2 mutation. It will be important to identify and reduce barriers to preventive surgery in the Bahamas in order that the benefit of getting testing can be fully realized.

Poly (ADP-ribose) polymerase inhibitors exhibit strong activity for treating the DNA damage repair defect in patients with prostate carcinoma (PCa). Although conventional DNA-damaging agents can theoretically lead to synthetic antitumoral effects, no report has clearly mentioned the clinical use of cisplatin for treating PCa patients with the breast cancer gene (BRCA)2 mutation. We administered 80 mg/m2 cisplatin triweekly to a patient with metastatic castration-resistant PCa (mCRPC) with the BRCA2 mutation, and after ten cycles, the prostate-specific antigen was dramatically decreased. We suggest that BRCA2 mutations may indicate the use of cisplatin for treating patients with mCRPC., Highlights • DNA damage repair defect may be a key as a treatment target for prostate carcinoma. • No clear report of cisplatin-use in prostate carcinoma with BRCA2 mutation. • Cisplatin was effective in a patient with prostate carcinoma with BRCA2 mutation.

Highlights • BRCA1/2 carriers are at high risk for fallopian tube carcinoma, which can arise in the proximal fallopian tube. • Pathologic analysis of RRBSO specimens should include serial sectioning of the entire tube, not just the fimbriated end. • Concurrent hysterectomy at time of RRBSO may be considered to ensure all tubal epithelium is resected., Patients with BRCA mutations are at high risk of high grade serous ovarian cancer. A paradigm shift has resulted in the current understanding that many cases of ovarian cancer actually arise from the fimbriated fallopian tube. The case presented here involves fallopian tube carcinoma arising from the cornua of the uterus in a BRCA2 carrier. This case suggests that pathologic analysis of risk-reducing bilateral salpingo-oophorectomy (RRBSO) specimens via serial sectioning and extensively examining the fimbriated end (SEE-FIM) may be insufficient to diagnose all occult lesions of interest. This case also provides a new consideration in the ongoing debate over the role of concurrent hysterectomy at time of RRBSO in BRCA carriers.

According to clinical guidelines, the occurrence of very early-onset breast cancer (VEO-BC) (diagnosed ≤ age 30 years) or VEO ovarian cancer (VEO-OC) (diagnosed ≤ age 40 years) in families with BRCA1 or BRCA2 mutation (BRCAm) prompts advancing the age of risk-reducing strategies in relatives. This study aimed to assess the relation between the occurrence of VEO-BC or VEO-OC in families with BRCAm and age at BC or OC diagnosis in relatives. We conducted a retrospective multicenter study of 448 consecutive families with BRCAm from 2003 to 2018. Mean age and 5-year–span distribution of age at BC or OC in relatives were compared in families with or without VEO-BC or VEO-OC. Conditional probability calculation and Cochran–Mantel–Haenszel chi-square tests were used to investigate early-onset cancer occurrence in relatives of VEO-BC and VEO-OC cases. Overall, 15% (19/245) of families with BRCA1m and 9% (19/203) with BRCA2m featured at least one case of VEO-BC, 8% (37/245) and 2% (2/203) featured at least one case of VEO-OC, respectively. The cumulative prevalence of VEO-BC was 5.1% (95% CI 3.6–6.6) and 2.5% (95% CI 1.4–3.6) for families with BRCA1m and BRCA2m, respectively. The distribution of age and mean age at BC diagnosis in relatives did not differ by occurrence of VEO-BC for families with BRCA1m or BRCA2m. Conditional probability calculations did not show an increase of early-onset BC in VEO-BC families with BRCA1m or BRCA2m. Conversely, the probability of VEO-BC was not increased in families with early-onset BC. VEO-BC or VEO-OC occurrence may not be related to young age at BC or OC onset in relatives in families with BRCAm. This finding—together with a relatively high VEO-BC risk for women with BRCAm—advocates for MRI breast screening from age 25 regardless of family history.

Background: Germline BRCA2 mutations increase risk of breast cancer and other malignancies. BRCA2 has been shown to play a role in telomere protection and maintenance. Telomere length (TL) has been studied as a modifying factor for various diseases, including breast cancer. Previous research on TL in BRCA mutation carriers has produced contradicting results. Methods: We measured blood TL, using a high-throughput monochrome multiplex qPCR method, in a well-defined Icelandic cohort of female BRCA2 mutation carriers (n = 169), sporadic breast cancer patients (n = 561), and healthy controls (n = 537). Results: Breast cancer cases had significantly shorter TL than unaffected women (P < 0.0001), both BRCA2 mutation carriers (P = 0.0097) and noncarriers (P = 0.00006). Using exclusively samples acquired before breast cancer diagnosis, we found that shorter telomeres were significantly associated with increased breast cancer risk in BRCA2 mutation carriers [HR, 3.60; 95% confidence interval (CI), 1.17–11.28; P, 0.025] but not in non-carriers (HR,1.40; 95% CI, 0.89–2.22; P, 0.15). We found no association between TL and breast cancer–specific survival. Conclusions: Blood TL is predictive of breast cancer risk in BRCA2 mutation carriers. Breast cancer cases have significantly shorter TL than unaffected women, regardless of BRCA2 status, indicating that samples taken after breast cancer diagnosis should not be included in evaluations of TL and breast cancer risk. Impact: Our study is built on a well-defined cohort, highly accurate methods, and long follow-up and can therefore help to clarify some previously published, contradictory results. Our findings also suggest that BRCA2 has an important role in telomere maintenance, even in normal blood cells. Cancer Epidemiol Biomarkers Prev; 26(8); 1248–54. ©2017 AACR.

The present case is the first report in Japan in which a breast cancer was discovered as a result of prospective magnetic resonance imaging (MRI) screening study for BRCA1/2 mutation carriers who were free of breast or ovarian cancer. This case is significant and it verifies the importance of MRI screening in breast or ovarian cancer-free BRCA1/2 mutation carriers who do not exhibit positive mammographic or ultrasonographic findings.

Purpose. The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC) and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. Methods. Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. Results. Out of a total of 1964 patients, 190 (10%) patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p=0.0003) compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p<0.0001, p=0.0007). A prior history of breast cancer was significantly associated with TNBC (p=0.0003). There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. Conclusions. We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

The genotype-phenotype correlations are quite often revealed in children with Wilm’s tumor. Phenotypedriven mutation detection provides the opportunity to predict a disease, to define and work out personal treatment course considering all the risks of possible complications. The article presents data on the main syndromes and genetically determined diseases associated with Wilm’s tumor. Patients with some WT1 associated syndromes (including WAGR and Denis–Drash), Perlman syndromes, the mosaic aneuploidy and Fanconi anemia due to biallelic BRCA2 mutation are at high risk of Wilm’s tumor development (>20%). Moderate risk of nephroblastoma development (5–20%) is registered in children with Fraser syndrome, Beckwith–Wiedemann syndrome with 11p15 disomy, and Sympson–Golabi–Behmel syndrome. Patients with the isolated hemihyipertrophy, Blооm syndrome, Li–Fraumeni syndrome, hyperparathyroid-jaw tumor (HPT-JT) syndromes, Mulibrey nanism, and other chromosomal aberrations seem to be at low risk for nephroblastoma (