7 results on '"Rimel, Bobbie"'
Search Results
2. DNA methylation and transcriptomic features are preserved throughout disease recurrence and chemoresistance in high grade serous ovarian cancers
- Author
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Gull, Nicole, Jones, Michelle R, Peng, Pei-Chen, Coetzee, Simon G, Silva, Tiago C, Plummer, Jasmine T, Reyes, Alberto Luiz P, Davis, Brian D, Chen, Stephanie S, Lawrenson, Kate, Lester, Jenny, Walsh, Christine, Rimel, Bobbie J, Li, Andrew J, Cass, Ilana, Berg, Yonatan, Govindavari, John-Paul B, Rutgers, Joanna KL, Berman, Benjamin P, Karlan, Beth Y, and Gayther, Simon A
- Subjects
Human Genome ,Genetics ,Ovarian Cancer ,Clinical Research ,Cancer ,Rare Diseases ,Orphan Drug ,Aetiology ,2.1 Biological and endogenous factors ,DNA Methylation ,Drug Resistance ,Neoplasm ,Female ,Humans ,Neoplasm Recurrence ,Local ,Ovarian Neoplasms ,Transcriptome ,High grade serous ovarian cancer ,Methylation ,Chemoresistance ,Epigenetics ,Whole genome bisulfite sequencing ,Computational methods ,Translational research ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundLittle is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC).MethodsWe performed whole genome bisulfite sequencing and transcriptome sequencing in 62 primary and recurrent tumors from 28 patients with stage III/IV HGSOC, of which 11 patients carried germline, pathogenic BRCA1 and/or BRCA2 mutations.ResultsLandscapes of genome-wide methylation (on average 24.2 million CpGs per tumor) and transcriptomes in primary and recurrent tumors showed extensive heterogeneity between patients but were highly preserved in tumors from the same patient. We identified significant differences in the burden of differentially methylated regions (DMRs) in tumors from BRCA1/2 compared to non-BRCA1/2 carriers (mean 659 DMRs and 388 DMRs in paired comparisons respectively). We identified overexpression of immune pathways in BRCA1/2 carriers compared to non-carriers, implicating an increased immune response in improved survival (P = 0.006) in these BRCA1/2 carriers.ConclusionThese findings indicate methylome and gene expression programs established in the primary tumor are conserved throughout disease progression, even after extensive chemotherapy treatment, and that changes in methylation and gene expression are unlikely to serve as drivers for chemoresistance in HGSOC.
- Published
- 2022
3. Phase II trial of cisplatin, gemcitabine and pembrolizumab for platinum-resistant ovarian cancer.
- Author
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Walsh, Christine S, Kamrava, Mitchell, Rogatko, Andre, Kim, Sungjin, Li, Andrew, Cass, Ilana, Karlan, Beth, and Rimel, Bobbie J
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Orphan Drug ,Ovarian Cancer ,Rare Diseases ,Cancer ,6.1 Pharmaceuticals ,General Science & Technology - Abstract
ObjectiveTo evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer.MethodsPatients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3-6 and as maintenance monotherapy in cycles 7-34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival.ResultsAn interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual.ConclusionsThe addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.
- Published
- 2021
4. Breast Cancer Surveillance Following Ovarian Cancer in BRCA Mutation Carriers
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Fong, Abigail, Cass, Ilana, John, Catherine, Gillen, Jessica, Moore, Kathleen M, Gangi, Alexandra, Walsh, Christine, Li, Andrew J, Rimel, Bobbie J, Karlan, Beth Y, and Amersi, Farin
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Prevention ,Cancer ,Ovarian Cancer ,Genetic Testing ,Clinical Research ,Patient Safety ,Rare Diseases ,Breast Cancer ,Good Health and Well Being ,Aged ,Aged ,80 and over ,BRCA1 Protein ,BRCA2 Protein ,Breast Neoplasms ,Carcinoma ,Ovarian Epithelial ,Female ,Humans ,Mammography ,Mastectomy ,Middle Aged ,Mutation ,Neoplasm Staging ,Population Surveillance ,Retrospective Studies ,surveillance ,BRCA mutation carriers ,breast cancer risk ,Clinical Sciences ,Surgery ,Clinical sciences - Abstract
BRCA1 or 2 mutations result in higher cancer risk for breast cancer (BC) and epithelial ovarian cancer (EOC) for carriers than exists in the general population. Optimal breast imaging surveillance in these patients has not been well defined. An Institutional Review Board-approved, multi-institutional retrospective chart review was performed. Patients diagnosed with BRCA-associated EOC between 1990-2015 were identified; demographic and clinical data were collected and analyzed. 192 BRCA mutation-positive patients with EOC were identified. 16/192 (8.3%) women were diagnosed with BC following EOC, at a median of 50 (range 5-327) months following EOC diagnosis and median age 59.5 (45-84) years. Breast cancer was most commonly detected on mammogram 7/16 (44%) or clinical exam 7/16 (44%). 2/16 (12.5%) had occult BC found during risk-reducing mastectomy. 14 (88%) had early-stage (0-2) disease. At mean follow-up of 8.1 years, 6 (37.5%) patients with BC following EOC had died due to EOC. The risk of BC diagnosis following EOC in BRCA mutation carriers is low; most of these BCs are early stage and diagnosed with mammography or physical exam. Overall, survival in BRCA mutation carriers is dominated by EOC-related mortality. Breast cancer surveillance in BRCA mutation carriers following EOC should prioritize nonsurgical strategies.
- Published
- 2020
5. Adult height is associated with increased risk of ovarian cancer: a Mendelian randomisation study
- Author
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Dixon-Suen, Suzanne C, Nagle, Christina M, Thrift, Aaron P, Pharoah, Paul DP, Ewing, Ailith, Pearce, Celeste Leigh, Zheng, Wei, Australian Ovarian Cancer Study Group, Chenevix-Trench, Georgia, Fasching, Peter A, Beckmann, Matthias W, Lambrechts, Diether, Vergote, Ignace, Lambrechts, Sandrina, Van Nieuwenhuysen, Els, Rossing, Mary Anne, Doherty, Jennifer A, Wicklund, Kristine G, Chang-Claude, Jenny, Jung, Audrey Y, Moysich, Kirsten B, Odunsi, Kunle, Goodman, Marc T, Wilkens, Lynne R, Thompson, Pamela J, Shvetsov, Yurii B, Dörk, Thilo, Park-Simon, Tjoung-Won, Hillemanns, Peter, Bogdanova, Natalia, Butzow, Ralf, Nevanlinna, Heli, Pelttari, Liisa M, Leminen, Arto, Modugno, Francesmary, Ness, Roberta B, Edwards, Robert P, Kelley, Joseph L, Heitz, Florian, du Bois, Andreas, Harter, Philipp, Schwaab, Ira, Karlan, Beth Y, Lester, Jenny, Orsulic, Sandra, Rimel, Bobbie J, Kjær, Susanne K, Høgdall, Estrid, Jensen, Allan, Goode, Ellen L, Fridley, Brooke L, Cunningham, Julie M, Winham, Stacey J, Giles, Graham G, Bruinsma, Fiona, Milne, Roger L, Southey, Melissa C, Hildebrandt, Michelle AT, Wu, Xifeng, Lu, Karen H, Liang, Dong, Levine, Douglas A, Bisogna, Maria, Schildkraut, Joellen M, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Bandera, Elisa V, Olson, Sara H, Salvesen, Helga B, Thomsen, Liv Cecilie Vestrheim, Kopperud, Reidun K, Bjorge, Line, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bruegl, Amanda, Cook, Linda S, Le, Nhu D, Swenerton, Kenneth D, Brooks-Wilson, Angela, Kelemen, Linda E, Lubiński, Jan, Huzarski, Tomasz, Gronwald, Jacek, Menkiszak, Janusz, Wentzensen, Nicolas, Brinton, Louise, Yang, Hannah, Lissowska, Jolanta, Høgdall, Claus K, Lundvall, Lene, Song, Honglin, Tyrer, Jonathan P, Campbell, Ian, Eccles, Diana, Paul, James, Glasspool, Rosalind, Siddiqui, Nadeem, and Whittemore, Alice S
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Women's Health ,Cancer ,Ovarian Cancer ,Prevention ,Rare Diseases ,2.1 Biological and endogenous factors ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Body Height ,Carcinoma ,Ovarian Epithelial ,Case-Control Studies ,Female ,Genetic Predisposition to Disease ,Geography ,Humans ,Mendelian Randomization Analysis ,Middle Aged ,Ovarian Neoplasms ,Risk Factors ,Young Adult ,Australian Ovarian Cancer Study Group ,Ovarian Cancer Association Consortium ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundObservational studies suggest greater height is associated with increased ovarian cancer risk, but cannot exclude bias and/or confounding as explanations for this. Mendelian randomisation (MR) can provide evidence which may be less prone to bias.MethodsWe pooled data from 39 Ovarian Cancer Association Consortium studies (16,395 cases; 23,003 controls). We applied two-stage predictor-substitution MR, using a weighted genetic risk score combining 609 single-nucleotide polymorphisms. Study-specific odds ratios (OR) and 95% confidence intervals (CI) for the association between genetically predicted height and risk were pooled using random-effects meta-analysis.ResultsGreater genetically predicted height was associated with increased ovarian cancer risk overall (pooled-OR (pOR) = 1.06; 95% CI: 1.01-1.11 per 5 cm increase in height), and separately for invasive (pOR = 1.06; 95% CI: 1.01-1.11) and borderline (pOR = 1.15; 95% CI: 1.02-1.29) tumours.ConclusionsWomen with a genetic propensity to being taller have increased risk of ovarian cancer. This suggests genes influencing height are involved in pathways promoting ovarian carcinogenesis.
- Published
- 2018
6. Breast Cancer Following Ovarian Cancer in BRCA Mutation Carriers
- Author
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Gangi, Alexandra, Cass, Ilana, Paik, Daniel, Barmparas, Galinos, Karlan, Beth, Dang, Catherine, Li, Andrew, Walsh, Christine, Rimel, Bobbie J, and Amersi, Farin F
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Breast Cancer ,Ovarian Cancer ,Prevention ,Cancer ,Rare Diseases ,Biomedical Imaging ,Clinical Research ,Adult ,Aged ,Aged ,80 and over ,BRCA1 Protein ,Breast Neoplasms ,DNA Mutational Analysis ,DNA ,Neoplasm ,Diagnosis ,Differential ,Female ,Humans ,Incidence ,Magnetic Resonance Imaging ,Middle Aged ,Mutation ,Neoplasms ,Multiple Primary ,Ovarian Neoplasms ,Retrospective Studies ,Survival Rate ,United States ,Clinical sciences - Abstract
ImportanceBRCA mutation carriers are at increased risk of developing breast cancer. However, the incidence of breast cancer after a diagnosis of epithelial ovarian cancer (EOC), one of the tubal/peritoneal cancers collectively referred to as pelvic serous carcinomas, is not well known. Optimal breast cancer surveillance and detection for these patients have also not been well characterized.ObjectivesTo determine the incidence of breast cancer after a diagnosis of EOC and to evaluate the need for breast cancer surveillance for these patients.Design, setting, and participantsA retrospective database review of 364 patients who underwent BRCA mutation testing for EOC (stages I-IV) between 1998 and 2012 at an academic medical center with gynecologic and breast cancer centers.Main outcomes and measuresIncidence of breast cancer and methods of surveillance.ResultsOf 364 patients, 135 (37.1%) were found to carry a germline BRCA1 or BRCA2 mutation. The mean age of patients at diagnosis of EOC was 49.5 years (range, 28-89 years). Of the 135 patients, 12 (8.9%) developed breast cancer. The median time from diagnosis of EOC to diagnosis of breast cancer was 50.5 months. Annual mammography was performed for 80 patients (59.3%), with annual magnetic resonance imaging of the breasts performed for 60 patients (44.4%). Thirteen patients (9.6%) underwent a bilateral prophylactic mastectomy at a median of 23 months following EOC diagnosis. Breast cancer was most commonly diagnosed by mammography for 7 of the 12 patients (58.3%), 3 (25.0%) of whom had a palpable mass and 2 (16.7%) of whom had incidental breast cancer detected during a prophylactic mastectomy. Seven patients with breast cancer (58.3%) underwent a bilateral mastectomy. All patients had early-stage breast cancer (stages 0-II). Four patients (33.3%) received adjuvant chemotherapy. At a median follow-up of 6.3 years, 4 of the 12 patients (33.3%) died of recurrent EOC after a diagnosis of breast cancer. The overall 10-year survival rate for the entire cohort of 135 patients was 17.0%.Conclusions and relevanceThe risk of metachronous breast cancer is low in patients with known BRCA mutations and EOC. A majority of these cases of breast cancer at an early stage are detected by use of mammography. Despite the small number of patients in our study, these results suggest that optimal breast cancer surveillance for patients with BRCA-associated EOC needs to be reevaluated given the low incidence of breast cancer among these high-risk patients. Confirmation of our findings from larger studies seems to be indicated.
- Published
- 2014
7. P26 Mechanisms of response and resistance to epigenetic therapies in ovarian cancer.
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Huang, Dandi, Abassi, Forough, Modak, Maya, Ellis, Leigh, Rimel, Bobbie, Haro, Marcela, and Lawrenson, Kate
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OVARIAN cancer , *CANCER treatment , *EPIGENETICS - Published
- 2023
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