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Niek van Wietmarschen, Andre Nussenzweig
Two recent studies implicate PARP as sensors of incompletely processed Okazaki fragments, changing our view about how single-strand breaks arise in unperturbed cells. Unligated Okazaki fragments may trigger homologous recombination-mediated repair and underpin genome instability in BRCA1/BRCA2-deficient cancers.
September 20, 2018: Molecular Cell
Cristina Cruz, Alba Llop-Guevara, Judy E Garber, Banu K Arun, José A Pérez Fidalgo, Ana Lluch, Melinda L Telli, Cristian Fernández, Carmen Kahatt, Carlos M Galmarini, Arturo Soto-Matos, Vicente Alfaro, Aitor Pérez de la Haza, Susan M Domchek, Silvia Antolin, Linda Vahdat, Nadine M Tung, Rafael Lopez, Joaquín Arribas, Ana Vivancos, José Baselga, Violeta Serra, Judith Balmaña, Steven J Isakoff
PURPOSE: This multicenter phase II trial evaluated lurbinectedin (PM01183), a selective inhibitor of active transcription of protein-coding genes, in patients with metastatic breast cancer. A unicenter translational substudy assessed potential mechanisms of lurbinectedin resistance. PATIENTS AND METHODS: Two arms were evaluated according to germline BRCA1/2 status: BRCA1/2 mutated (arm A; n = 54) and unselected ( BRCA1/2 wild-type or unknown status; arm B; n = 35)...
September 21, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
J J Bakhuizen, M E Velthuizen, S Stehouwer, E M Bleiker, M G Ausems
Germline TP53 mutations are associated with an increased risk of early-onset breast cancer. Traditionally, it was not standard practice to offer TP53 genetic testing due to the low mutation detection rate and limited options regarding preventive screening. Recent guidelines recommend that all women diagnosed with breast cancer before the age of 31, irrespective of family history, should be offered TP53 genetic testing. This study aims to gain more knowledge on the attitudes and experiences among genetics professionals regarding the timing and content of genetic counselling of young breast cancer patients for Li-Fraumeni syndrome (LFS)...
September 20, 2018: Familial Cancer
Jeremy L Warner, Ishaan Prasad, Makiah Bennett, Monica Arniella, Alicia Beeghly-Fadiel, Kenneth D Mandl, Gil Alterovitz
Purpose: Data standards and interoperability are critical for improving care for patients with cancer. Recent efforts by ASCO include the Data Standards and Interoperability Summit in 2016, which led to the Omics and Precision Oncology and Advancing Interoperability workshops. To facilitate improved patient care, several recommendations for data sharing and standardization were made to the community. Methods: To address these recommendations, we developed SMART Cancer Navigator, a Web application that uses application programming interfaces to gather clinical and genomic data from 11 public knowledge bases ranging from basic to clinical content coverage; three (CIViC, ClinVar, and OncoKB) explicitly linked genomic variants to clinical factors such as prognosis and treatment selection...
2018: JCO Precision Oncology
Niu Yizhen, Li Kemin, Li Qingli, Wang Danqing, Yin Rutie, Song Liang
RATIONALE: The breast cancer susceptibility gene (BRCA) is an important tumor suppressor gene and tumor susceptibility gene. Germ line BRCA1/2 mutations significantly increase the risk of breast cancer and other cancers in women. PATIENT CONCERNS: A 48-year-old woman was diagnosed with breast cancer at the age of 42 and subsequently diagnosed with ovarian cancer at the age of 48. Her sister had a history of breast cancer and her mother died from ovarian cancer. DIAGNOSES: The patient has a family history of tumors...
September 2018: Medicine (Baltimore)
Saba Jalali, Nitin Shivappa, James R Hébert, Zeinab Heidari, Azita Hekmatdoost, Bahram Rashidkhani
Chronic inflammation is implicated in breast cancer (BrCa) development; however, studies on the association of the inflammatory potential of diet and breast cancer have produced conflicting results. With this as background, we investigated the association between dietary inflammatory index (DII® ) scores and BrCa risk in an Iranian case-control study. In this study, 136 newly diagnosed breast cancer patients and 272 hospitalized controls were recruited using convenience sampling. DII scores were computed from dietary intake data collected through a validated food frequency questionnaire (FFQ)...
September 20, 2018: Nutrition and Cancer
Ilaria Plantamura, Giulia Cosentino, Alessandra Cataldo
MicroRNAs are a class of small non-coding regulatory RNAs playing key roles in cancer. Breast cancer is the most common female malignancy worldwide and is categorized into four molecular subtypes: luminal A and B, HER2+ and triple-negative breast cancer (TNBC). Despite the development of multiple targeted therapies for luminal and HER2+ breast tumors, TNBC lacks specific therapeutic approaches, thus they are treated mainly with radio- and chemotherapy. The effectiveness of these therapeutic regimens is based on their ability to induce DNA damage, which is differentially resolved and repaired by normal vs...
2018: Frontiers in Oncology
Mark D Pegram, Yu Zong, Clinton Yam, Matthew P Goetz, Stacy L Moulder
Metastatic breast cancer continues to be a life-threatening diagnosis that impacts hundreds of thousands of patients around the world. Targeted therapies are usually associated with less toxicity compared with cytotoxic chemotherapies and often induce response or durable disease control in estrogen receptor (ER) and/or HER2+ breast cancers. Drugs that target CDK 4/6 either alone or in combination with endocrine therapy have demonstrated substantial improvements in progression-free survival (PFS) compared with endocrine monotherapy...
May 23, 2018: American Society of Clinical Oncology Educational Book
Carolina Velázquez, Eva M Esteban-Cardeñosa, Enrique Lastra, Luis E Abella, Virginia de la Cruz, Carmen D Lobatón, Mercedes Durán, Mar Infante
BRIP1 is a component of the Fanconi Anemia/BRCA pathway responsible for DNA reparation via helicase activity. Some heterozygous variants in BRIP1 could contribute to Hereditary Breast Cancer through a defective DNA repair. The clinical utility of BRIP1 mutations in a familial cancer context is compromised by the conflicting interpretation of "variants of uncertain significance" (VUS). Defining the clinical significance of variants identified in genetic tests is a major challenge; therefore, studies that evaluate the biological effect of these variants are definitely necessary...
September 19, 2018: Molecular Carcinogenesis
Shuren Zhang, Hao Yuan, Yan Guo, Kun Wang, Xiaoyong Wang, Zijian Guo
Two PtIV-artesunate anticancer prodrugs that target RAD51, a crucial protein in homologous recombination mediating the sensitivity of cancer cells to DNA-damaging agents, were designed; their cytotoxicities against BRCA-proficient ovarian and breast cancer cells are significantly higher than those of cisplatin.
September 19, 2018: Chemical Communications: Chem Comm
Christian Marth
BACKGROUND: The challenges of managing relapsed ovarian cancer increase as more advanced lines of chemotherapy are achieved. METHODS: A case study is presented to illustrate the complexities of selecting treatment in a patient with platinum-sensitive relapsed ovarian cancer and exposure to two previous lines of platinum-based chemotherapy. RESULTS: In this clinical scenario, options include re-treatment with platinum-based chemotherapy or treatment with a nonplatinum single-agent or a nonplatinum combination...
October 2018: Expert Review of Anticancer Therapy
Nicoletta Colombo
OBJECTIVES: Ovarian cancer patients with relapse 6-12 months after last platinum treatment, who have received bevacizumab consolidation and are not BRCA mutant, represent a considerable therapeutic challenge. METHODS: By means of illustrative case study, this review evaluates various treatment strategies for use at first relapse in an ovarian cancer patient with limited sensitivity to platinum. RESULTS: Clinical parameters predictive of complete resection in secondary cytoreductive surgery include an Eastern Cooperative Oncology Group performance status of 0, no residual disease after first surgery, and <500 mL of ascites...
October 2018: Expert Review of Anticancer Therapy
Zhu Wang, Jianwen Zhang, Ying Zhang, Qiong Deng, Hui Liang
Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) are the most well‑known genes linked to breast cancer and ovarian cancer, which are crucial in DNA repair and transcriptional regulation. The present study aimed to elucidate the expression profiles, mutations and interaction networks of BRCA1 and BRCA2, which may provide insights to reveal the mechanisms of BRCA genes ultimately leading to breast or ovarian tumorigenesis. Bioinformatics analyses were performed in the present study. The mRNA levels of BRCA1 and BRCA2 were evaluated using FIREHOSE analysis, SAGE Genie tools and Oncomine analysis...
September 11, 2018: International Journal of Molecular Medicine
Brian D Gonzalez, Aasha I Hoogland, Monica L Kasting, Deborah Cragun, Jongphil Kim, Kimlin Ashing, Cheryl L Holt, Chanita Hughes Halbert, Tuya Pal, Susan T Vadaparampil
OBJECTIVE: Prior studies demonstrating minimal psychological consequences for women receiving genetic counseling/genetic testing (GC/GT) for hereditary breast and ovarian cancer rely on predominantly Caucasian women. We conducted a prospective follow-up of a subset of participants from a population-based study of Black breast cancer (BC) survivors receiving GC/GT for BRCA1 and BRCA2 mutations. METHODS: Black women with invasive BC at age ≤50 years diagnosed between 2009-2012 were recruited through the Florida Cancer Registry...
September 12, 2018: Psycho-oncology
Klaus Pietzner, Sara Nasser, Sara Alavi, Silvia Darb-Esfahani, Mona Passler, Mustafa Zelal Muallem, Jalid Sehouli
The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics...
November 2018: Journal of Gynecologic Oncology
Omalkhair Abulkhair, Mohammed Al Balwi, Ola Makram, Lamia Alsubaie, Medhat Faris, Hussam Shehata, Ahmed Hashim, Banu Arun, Ahmed Saadeddin, Ezzeldin Ibrahim
Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations...
August 2018: Journal of Global Oncology
Xiaofan Han, Jun Tang, Tong Chen, Guosheng Ren
There are increasing reports of aberrant expression of GATA4, correlated with oncogenesis and malignant progression in some solid tumors, but whether GATA4 functions as an oncogenic driver or a tumor suppressor in carcinogenesis remains controversial. Because the role and mechanism of GATA4 in breast cancer (BrCa) remain poorly understood, we focused on the expression of GATA4 in BrCa cell lines and tissues and its mechanism in breast oncogenesis. Semiquantitative real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR, Western blot analysis, and immunohistochemistry were used to detect expression of GATA4 in BrCa cell lines and adjacent breast tissues...
September 6, 2018: Journal of Cellular Biochemistry
Angela R Solano, Natalia C Liria, Fernanda S Jalil, Daniela M Faggionato, Pablo G Mele, Alejandra Mampel, Florencia C Cardoso, Ernesto J Podesta
In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk breast and ovarian cancer cases in that ethnic group. Few studies with limited number of genotyped individuals have expanded the spectrum of mutations in both BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual AJ were counseled at CEMIC (Centro de Educación Médica e Investigaciones Clínicas), and were genotyped first for the 3 recurrent mutation panel followed by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested negative for the first genotyping step...
2018: Frontiers in Oncology
Haixia Chen, Jianming Wu, Zhihong Zhang, Yong Tang, Xiaoxuan Li, Shuangqing Liu, Shousong Cao, Xianzhu Li
Triple-negative breast cancer (TNBC) is a subtype of aggressive breast cancer and characterized by a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. BRCA genes are tumor-suppressor genes that are involved in DNA damage repair and mutations of BRCA genes may increase the risk of developing breast cancer and/or ovarian cancer due to defective DNA repair mechanisms. However, the relationship between BRCA status and TNBC needs to be further investigated and validated...
2018: Frontiers in Pharmacology
J Tanner Ringley, Donald C Moore, Jolly Patel, Maegan S Rose
Objective: To review the pharmacology, safety, efficacy, and role of poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors in the treatment and maintenance of relapsed, advanced ovarian cancer. Summary: A total of 3 phase 2 trials and 2 phase 3 trials were reviewed that evaluated the safety and efficacy of oral niraparib, olaparib, and rucaparib in patients with ovarian cancer. Progression-free survival (PFS) was evaluated in the maintenance setting for niraparib and olaparib, resulting in a PFS of 21...
September 2018: P & T: a Peer-reviewed Journal for Formulary Management
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