Obstetrics and Gynecology Commons^™

The Application Of An Extracellular Vesicle-Based Biosensor In Early Diagnosis And Prediction Of Chemoresponsiveness In Ovarian Cancer, Meshach Asare-Werehene, Robert A Hunter, Emma Gerber, Arkadiy Reunov, Isaiah Brine, Chia-Yu Chang, Chia-Ching Chang, Dar-Bin Shieh, Dylan Burger, Hanan Anis, Benjamin K Tsang

Faculty, Staff and Student Publications

BACKGROUND: Ovarian cancer (OVCA) is the most fatal gynecological cancer with late diagnosis and plasma gelsolin (pGSN)-mediated chemoresistance representing the main obstacles to treatment success. Since there is no reliable approach to diagnosing patients at an early stage as well as predicting chemoresponsiveness, there is an urgent need to develop a diagnostic platform for such purposes. Small extracellular vesicles (sEVs) are attractive biomarkers given their potential accuracy for targeting tumor sites.

METHODS: We have developed a novel biosensor which utilizes cysteine-functionalized gold nanoparticles that simultaneously bind to cisplatin (CDDP) and plasma/cell-derived EVs, affording us the advantage of predicting OVCA chemoresponsiveness, …

Anthracycline-Containing And Taxane-Containing Chemotherapy For Early-Stage Operable Breast Cancer: A Patient-Level Meta-Analysis Of 100 000 Women From 86 Randomised Trials, Early Breast Cancer Trialists’ Collaborative Group (Ebctcg)

Faculty, Staff and Student Publications

BACKGROUND: Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens.

METHODS: We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including …

Temporal Machine Learning Analysis Of Prior Mammograms For Breast Cancer Risk Prediction, Hui Li, Kayla Robinson, Li Lan, Natalie Baughan, Chun-Wai Chan, Matthew Embury, Gary J Whitman, Randa El-Zein, Isabelle Bedrosian, Maryellen L Giger

Faculty, Staff and Student Publications

The identification of women at risk for sporadic breast cancer remains a clinical challenge. We hypothesize that the temporal analysis of annual screening mammograms, using a long short-term memory (LSTM) network, could accurately identify women at risk of future breast cancer. Women with an imaging abnormality, which had been biopsy-confirmed to be cancer or benign, who also had antecedent imaging available were included in this case-control study. Sequences of antecedent mammograms were retrospectively collected under HIPAA-approved guidelines. Radiomic and deep-learning-based features were extracted on regions of interest placed posterior to the nipple in antecedent images. These features were input to …

Prospective, Early Longitudinal Assessment Of Lymphedema-Related Quality Of Life Among Patients With Locally Advanced Breast Cancer: The Foundation For Building A Patient-Centered Screening Program, Anusha Gandhi, Tianlin Xu, Sarah M Desnyder, Grace L Smith, Ruitao Lin, Carlos H Barcenas, Michael C Stauder, Karen E Hoffman, Eric A Strom, Susan Ferguson, Benjamin D Smith, Wendy A Woodward, George H Perkins, Melissa P Mitchell, Desmond Garner, Chelain R Goodman, Melissa Aldrich, Marigold Travis, Susan Lilly, Isabelle Bedrosian, Simona F Shaitelman

Faculty, Staff and Student Publications

BACKGROUND: We examined how breast cancer-related lymphedema (BCRL) affects health-related quality of life (HRQOL), productivity, and compliance with therapeutic interventions to guide structuring BCRL screening programs.

METHODS: We prospectively followed consecutive breast cancer patients who underwent axillary lymph node dissection (ALND) with arm volume screening and measures assessing patient-reported health-related quality of life (HRQOL) and perceptions of BCRL care. Comparisons by BCRL status were made with Mann-Whitney U, Chi-square, Fisher's exact, or t tests. Trends over time from ALND were assessed with linear mixed-effects models.

RESULTS: With a median follow-up of 8 months in 247 patients, 46% self-reported ever having …

Fear Of Recurrence, Emotional Well-Being And Quality Of Life Among Long-Term Advanced Ovarian Cancer Survivors, Kathryn Osann, Lari Wenzel, Chelsea Mckinney, Lynne Wagner, David Cella, Giulia Fulci, Mary J Scroggins, Heather A Lankes, Victoria Wang, Kenneth P Nephew, George L Maxwell, Samuel C Mok, Thomas P Conrads, Austin Miller, Michael Birrer

Faculty, Staff and Student Publications

OBJECTIVE: Although advanced stage epithelial ovarian cancer is widely considered life-threatening, 17% of women with advanced disease will survive long-term. Little is known about the health-related quality of life (QOL) of long-term ovarian cancer survivors, or how fear of recurrence might affect QOL.

METHODS: 58 long-term survivors with advanced disease participated in the study. Participants completed standardized questionnaires to capture cancer history, QOL, and fear of recurrent disease (FOR). Statistical analyses included multivariable linear models.

RESULTS: Participants averaged 52.8 years at diagnosis and had survived >8 years (mean:13.5); 64% had recurrent disease. Mean FACT-G, FACT-O, and FACT-O-TOI (TOI) scores were …

Cervicovaginal Microbiota Profiles In Precancerous Lesions And Cervical Cancer Among Ethiopian Women, Brhanu Teka, Kyoko Yoshida-Court, Ededia Firdawoke, Zewditu Chanyalew, Muluken Gizaw, Adamu Addissie, Adane Mihret, Lauren E Colbert, Tatiana Cisneros Napravnik, Molly B El Alam, Erica J Lynn, Melissa Mezzari, Jhingran Anuja, Eva Johanna Kantelhardt, Andreas M Kaufmann, Ann H Klopp, Tamrat Abebe

Faculty, Staff and Student Publications

Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used …

Exploiting Metabolic Vulnerabilities After Anti-Vegf Antibody Therapy In Ovarian Cancer, Deanna Glassman, Mark S Kim, Meredith Spradlin, Sunil Badal, Mana Taki, Pratip Bhattacharya, Prasanta Dutta, Charles V Kingsley, Katherine I Foster, Olamide Animasahun, Jin Heon Jeon, Abhinav Achreja, Anusha Jayaraman, Praveen Kumar, Minal Nenwani, Fulei Wuchu, Emine Bayraktar, Yutuan Wu, Elaine Stur, Lingegowda Mangala, Sanghoon Lee, Timothy A Yap, Shannon N Westin, Livia S Eberlin, Deepak Nagrath, Anil K Sood

Faculty, Staff and Student Publications

Despite modest clinical improvement with anti-vascular endothelial growth factor antibody (AVA) therapy in ovarian cancer, adaptive resistance is ubiquitous and additional options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance and we aimed to investigate the utility of a GLS inhibitor (GLSi). Our in vitro findings demonstrated increased glutamine abundance and a significant cytotoxic effect in AVA-resistant tumors when GLSi was administered in combination with bevacizumab. In vivo, GLSi led to a reduction in tumor growth as monotherapy and when combined with AVA. Furthermore, GLSi initiated after the emergence …

Adjuvant Chemotherapy Versus Adjuvant Concurrent Chemoradiotherapy After Radical Surgery For Early-Stage Cervical Cancer: A Randomized, Non-Inferiority, Multicenter Trial, Danhui Weng, Huihua Xiong, Changkun Zhu, Xiaoyun Wan, Yaxia Chen, Xinyu Wang, Youzhong Zhang, Jie Jiang, Xi Zhang, Qinglei Gao, Gang Chen, Hui Xing, Changyu Wang, Kezhen Li, Yaheng Chen, Yuyan Mao, Dongxiao Hu, Zimin Pan, Qingqin Chen, Baoxia Cui, Kun Song, Cunjian Yi, Guangcai Peng, Xiaobing Han, Ruifang An, Liangsheng Fan, Wei Wang, Tingchuan Xiong, Yile Chen, Zhenzi Tang, Lin Li, Xingsheng Yang, Xiaodong Cheng, Weiguo Lu, Hui Wang, Beihua Kong, Xing Xie, Ding Ma

Faculty, Staff and Student Publications

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant …

Combination Of Epha2- And Wee1-Targeted Therapies In Endometrial Cancer, Santosh K Dasari, Robiya Joseph, Sujanitha Umamaheswaran, Lingegowda S Mangala, Emine Bayraktar, Cristian Rodriguez-Aguayo, Yutuan Wu, Nghi Nguyen, Reid T Powell, Mary Sobieski, Yuan Liu, Mamur A Chowdhury, Paola Amero, Clifford Stephan, Gabriel Lopez-Berestein, Shannon N Westin, Anil K Sood

Faculty, Staff and Student Publications

EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial …

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Faculty, Staff and Student Publications

No abstract provided.

Mixcan: A Framework For Cell-Type-Aware Transcriptome-Wide Association Studies With An Application To Breast Cancer, Xiaoyu Song, Jiayi Ji, Joseph H Rothstein, Stacey E Alexeeff, Lori C Sakoda, Adriana Sistig, Ninah Achacoso, Eric Jorgenson, Alice S Whittemore, Robert J Klein, Laurel A Habel, Pei Wang, Weiva Sieh

Faculty, Staff and Student Publications

Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared …

Immune Environment And Antigen Specificity Of The T Cell Receptor Repertoire Of Malignant Ascites In Ovarian Cancer, Kyoko Yoshida-Court, Tatiana V Karpinets, Aparna Mitra, Travis N Solley, Stephanie Dorta-Estremera, Travis T Sims, Andrea Y Delgado Medrano, Molly B El Alam, Mustapha Ahmed-Kaddar, Erica J Lynn, K Jagannadha Sastry, Jianhua Zhang, Andrew Futreal, Alpa Nick, Karen Lu, Lauren E Colbert, Ann H Klopp

Faculty, Staff and Student Publications

We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which …

Phase I Dose Escalation Study Of Topical Bexarotene In Women At High Risk For Breast Cancer, Parijatham S Thomas, Anisha B Patel, J Jack Lee, Diane D Liu, Mike Hernandez, Miguel Muzzio, Alejandro Contreras, Valerie Sepeda, Carrie Mays, Diane Weber, Lana A Vornik, Seema A Khan, Eileen Dimond, Brandy M Heckman-Stoddard, Marjorie Perloff, Powel H Brown

Faculty, Staff and Student Publications

Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Machine Learning-Driven Exploration Of Drug Therapies For Triple-Negative Breast Cancer Treatment, Aman Chandra Kaushik, Zhongming Zhao

Faculty, Staff and Student Publications

Breast cancer is the second leading cause of cancer death in women among all cancer types. It is highly heterogeneous in nature, which means that the tumors have different morphologies and there is heterogeneity even among people who have the same type of tumor. Several staging and classifying systems have been developed due to the variability of different types of breast cancer. Due to high heterogeneity, personalized treatment has become a new strategy. Out of all breast cancer subtypes, triple-negative breast cancer (TNBC) comprises ∼10%-15%. TNBC refers to the subtype of breast cancer where cells do not express estrogen receptors, …

Targeting Nuclear Hormone Receptors For The Prevention Of Breast Cancer, Cassandra L Moyer, Powel H Brown

Faculty, Staff and Student Publications

Advancements in research have led to the steady decline of breast cancer mortality over the past thirty years. However, breast cancer incidence has continued to rise, resulting in an undue burden on healthcare costs and highlighting a great need for more effective breast cancer prevention strategies, including targeted chemo preventative agents. Efforts to understand the etiology of breast cancer have uncovered important roles for nuclear receptors in the development and progression of breast cancer. Targeted therapies to inhibit estrogen receptor (ER) and progesterone receptor (PR) signaling (selective ER modulators, aromatase inhibitors and selective PR modulators) have shown great promise for …

Circulating Vitamin D And Breast Cancer Risk: An International Pooling Project Of 17 Cohorts, Kala Visvanathan, Alison M Mondul, Anne Zeleniuch-Jacquotte, Molin Wang, Mitchell H Gail, Shiaw-Shyuan Yaun, Stephanie J Weinstein, Marjorie L Mccullough, A Heather Eliassen, Nancy R Cook, Claudia Agnoli, Martin Almquist, Amanda Black, Julie E Buring, Chu Chen, Yu Chen, Tess Clendenen, Laure Dossus, Veronika Fedirko, Gretchen L Gierach, Edward L Giovannucci, Gary E Goodman, Marc T Goodman, Pascal Guénel, Göran Hallmans, Susan E Hankinson, Ronald L Horst, Tao Hou, Wen-Yi Huang, Michael E Jones, Corrine E Joshu, Rudolf Kaaks, Vittorio Krogh, Tilman Kühn, Marina Kvaskoff, I-Min Lee, Yahya Mahamat-Saleh, Johan Malm, Jonas Manjer, Gertraud Maskarinec, Amy E Millen, Toqir K Mukhtar, Marian L Neuhouser, Trude E Robsahm, Minouk J Schoemaker, Sabina Sieri, Malin Sund, Anthony J Swerdlow, Cynthia A Thomson, Giske Ursin, Jean Wactawski-Wende, Ying Wang, Lynne R Wilkens, Yujie Wu, Emilie Zoltick, Walter C Willett, Stephanie A Smith-Warner, Regina G Ziegler

Faculty, Staff and Student Publications

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, …

Effectiveness Without Efficacy: Cautionary Tale From A Landmark Breast Cancer Randomized Controlled Trial, Yu Shen, Jing Ning, Heather Y Lin, Simona F Shaitelman, Henry M Kuerer, Isabelle Bedrosian

Faculty, Staff and Student Publications

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data.

Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment …

Selinexor In Combination With Weekly Paclitaxel In Patients With Metastatic Solid Tumors: Results Of An Open Label, Single-Center, Multi-Arm Phase 1b Study With Expansion Phase In Ovarian Cancer, Shannon N Westin, Siqing Fu, Apostolia Tsimberidou, Sarina Piha-Paul, Fechukwu Akhmedzhanov, Bulent Yilmaz, Lacey Mcquinn, Amanda L Brink, Jing Gong, Cheuk Hong Leung, Heather Lin, David S Hong, Shubham Pant, Brett Carter, Amir Jazaeri, David Gershenson, Anil K Sood, Robert L Coleman, Jatin Shah, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

OBJECTIVE: Selinexor is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound which blocks Exportin-1 (XPO1). Our objective was to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of selinexor and weekly paclitaxel.

METHODS: This was an open label, single-center, multi-arm phase 1b study utilizing a "3 + 3" design and a "basket-type" expansion in recurrent solid tumors. Selinexor (60 mg or 80 mg twice weekly orally) and weekly paclitaxel (80 mg IV 2 week on, 1 week off) were one of 13 parallel arms. Efficacy was evaluated using RECIST version 1.1.

RESULTS: All 35 patients …

Huge Abdominopelvic Mass Arising From Cervical Fibroid Around An Infected Cervical Diverticulum: A Very Rare Case And A Review Of Literature, Arpita De, Reva Tripathi, Abhinav Jain, Safia Rana

Faculty, Staff and Student Publications

Primary uterine diverticula are a very rare congenital anomaly of the uterus with only 21 reported cases. Even rarer is the occurrence of primary cervical diverticula with only six cases reported so far. This is a unique case of a huge abdominopelvic mass arising from cervical fibroid around an infected cervical diverticulum. A 44 year-old, P4L4 came to the OPD with a eighteen weeks size abdomino-pelvic mass. She had a failed surgery 6 months back, attempted to remove the mass. Magnetic resonance imaging revealed a cervical diverticulum which possibly had a pus collection. Relaparotomy was done. It revealed a huge …

Feasibility Of Quantitative Diffusion-Weighted Imaging During Intra-Procedural Mri-Guided Brachytherapy Of Locally Advanced Cervical And Vaginal Cancers, Megan C Jacobsen, Bastien Rigaud, Samantha J Simiele, Gaiane M Rauch, Matthew S Ning, Sastry Vedam, Ann H Klopp, R Jason Stafford, Kristy K Brock, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Purpose: To determine the feasibility of quantitative apparent diffusion coefficient (ADC) acquisition during magnetic resonance imaging-guided brachytherapy (MRgBT) using reduced field-of-view (rFOV) diffusion-weighted imaging (DWI).

Methods and materials: T2-weighted (T2w) MR and full-FOV single-shot echo planar (ssEPI) DWI were acquired in 7 patients with cervical or vaginal malignancy at baseline and prior to brachytherapy, while rFOV-DWI was acquired during MRgBT following brachytherapy applicator placement. The gross target volume (GTV) was contoured on the T2w images and registered to the ADC map. Voxels at the GTV's maximum Maurer distance comprised a central sub-volume (GTVcenter). Contour ADC mean and standard deviation were …

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel D Kim, Sarah M Desnyder, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

BACKGROUND: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised.

METHODS: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed.

RESULTS: Data from 1764 patients were analysed (882 patients …

Targeting Tmem205 Mediated Drug Resistance In Ovarian Clear Cell Carcinoma Using Oncolytic Virus, Uksha Saini, Brentley Q Smith, Kalpana Deepa Priya Dorayappan, Ji Young Yoo, G Larry Maxwell, Balveen Kaur, Ikuo Konishi, David O'Malley, David E Cohn, Karuppaiyah Selvendiran

Faculty, Staff and Student Publications

BACKGROUND: Ovarian clear cell carcinoma (OCCC) accounts for approximately 8-10% of epithelial ovarian cancers in the United States. Although it is rare, OCCC usually presents with treatment challenges and the overall prognosis is far worse than high grade serous ovarian cancer HGSOC. The objective of this study was to examine the therapeutic relevance of combining oncolytic virus with cisplatin for ovarian cancer clear cell carcinoma (OCCC).

RESULTS: We identified that TMEM205, a recently discovered transmembrane protein, contributes to chemoresistance in OCCC cells via the exosomal pathway. Mechanistically, TMEM205 undergoes ligand-independent constitutive endocytosis and co-localizes with Rab11 to contribute to the …

Safety And Efficacy Of Hsp90 Inhibitor Ganetespib For Neoadjuvant Treatment Of Stage Ii/Iii Breast Cancer, Julie E Lang, Andres Forero-Torres, Douglas Yee, Christina Yau, Denise Wolf, John Park, Barbara A Parker, A Jo Chien, Anne M Wallace, Rashmi Murthy, Kathy S Albain, Erin D Ellis, Heather Beckwith, Barbara B Haley, Anthony D Elias, Judy C Boughey, Rachel L Yung, Claudine Isaacs, Amy S Clark, Hyo S Han, Rita Nanda, Qamar J Khan, Kristen K Edmiston, Erica Stringer-Reasor, Elissa Price, Bonnie Joe, Minetta C Liu, Lamorna Brown-Swigart, Emanuel F Petricoin, Julia D Wulfkuhle, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Adam L Asare, Jeffrey B Matthews, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van 'T Veer, Nola M Hylton, Angela M Demichele, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to …

Targeting The Mtor Pathway For The Prevention Of Er-Negative Breast Cancer, Abhijit Mazumdar, William M Tahaney, Jamal L Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandro Contreras, Michelle I Savage, Lana A Vornik, Shizuko Sei, Altaf Mohammed, Powel H Brown

Faculty, Staff and Student Publications

Our results show that everolimus delays mammary tumor formation in multiple mouse models, suggesting that mTOR inhibitors will be useful for the prevention of ER-negative and triple-negative breast cancer in humans. See related Spotlight, p. 787.

Adjuvant Therapy In Women With Early Stage Uterine Serous Carcinoma: A Multi-Institutional Study, Katherine C Kurnit, Silvana Pedra Nobre, Bryan M Fellman, David A Iglesias, Kristina Lindemann, Anuja Jhingran, Ane Gerda Z Eriksson, Beyhan Ataseven, Gretchen E Glaser, Jennifer J Mueller, Shannon N Westin, Pamela T Soliman

Faculty, Staff and Student Publications

OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma.

METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall …

Inclusion Of Premenopausal Women In Breast Cancer Clinical Trials, Kelsey L Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R Patel, Rachel M Layman, Sharon H Giordano, Wendy A Woodward, Benjamin D Smith, Simona F Shaitelman, Ethan B Ludmir

Faculty, Staff and Student Publications

BACKGROUND: Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

METHODS: Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

RESULTS: Of 170 breast …

Obstetric And Neonatal Outcomes 1 Or More Years After A Diagnosis Of Breast Cancer, Kirsten Jorgensen, Roni Nitecki, Hazel B Nichols, Shuangshuang Fu, Chi-Fang Wu, Alexander Melamed, Paula Brady, Mariana Chavez Mac Gregor, Mark A Clapp, Sharon Giordano, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.

METHODS: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December …

Cell-Free Dna Screening Positive For Monosomy X: Clinical Evaluation And Management Of Suspected Maternal Or Fetal Turner Syndrome, Tazim Dowlut-Mcelroy, Shanlee Davis, Susan Howell, Iris Gutmark-Little, Vaneeta Bamba, Siddharth Prakash, Sheetal Patel, Doris Fadoju, Nandini Vijayakanthi, Mary Haag, Deborrah Hennerich, Lorraine Dugoff, Roopa Kanakatti Shankar

Faculty, Staff and Student Publications

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, …

Lessons From The Failure To Complete A Trial Of Denosumab In Women With A Pathogenic Brca1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy, Meghna S Trivedi, Nadir Arber, Eitan Friedman, Judy E Garber, Kevin Holcomb, Neil S Horowitz, Jason D Wright, J Jack Lee, Lana A Vornik, Saba Abutaseh, Tawana Castile, Edward R Sauter, Eileen Dimond, Brandy M Heckman-Stoddard, Margaret House, Goli Samimi, Powel H Brown, Katherine D Crew

Faculty, Staff and Student Publications

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO …

Risk Factors For Community-Acquired Bacterial Infection Among Young Infants In South Asia: A Longitudinal Cohort Study With Nested Case-Control Analysis, Nicholas E Connor, Mohammad Shahidul Islam, Luke C Mullany, Nong Shang, Zulfiqar A Bhutta, Anita K M Zaidi, Sajid Soofi, Imran Nisar, Pinaki Panigrahi, Kalpana Panigrahi, Radhanath Satpathy, Anuradha Bose, Rita Isaac, Abdullah H Baqui, Dipak K Mitra, Qazi Sadeq-Ur Rahman, Tanvir Hossain, Stephanie J Schrag, Jonas M Winchell, Melissa L Arvay, Maureen H Diaz, Jessica L Waller, Martin W Weber, Davidson H Hamer, Patricia Hibberd, A S M Nawshad Uddin Ahmed, Maksuda Islam, Mohammad Belal Hossain, Shamim A Qazi, Shams El Arifeen, Gary L Darmstadt, Samir K Saha

Faculty, Staff and Student Publications

OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.

METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build …