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Article: HER2-directed therapy for metastatic breast cancer.

Jelovac, Danijela / Emens, Leisha A

2013 Volume 27, Issue 3, Page(s) 166–175

Abstract: Human epidermal growth factor receptor 2 (HER2) overexpression drives the biology of 20% of breast cancers, and predicts a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients with both early and ... ...

Abstract	Human epidermal growth factor receptor 2 (HER2) overexpression drives the biology of 20% of breast cancers, and predicts a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients with both early and metastatic breast cancer. Currently three HER2-targeted agents, trastuzumab (Herceptin), lapatinib (Tykerb), and pertuzumab (Perjeta), are available for the treatment of HER2-positive metastatic breast cancer (MBC). Numerous studies have attempted to optimize their use by combining them with each other, or with endocrine and cytotoxic therapies. Most recently, the FDA approved the combination of trastuzumab, pertuzumab, and docetaxel as first-line treatment for MBC, and in late February 2013 approved a fourth HER2-targeted agent, trastuzumab emtansine (T-DM1, Kadcyla), for accelerated approval. These advances create a number of clinical dilemmas, including identification of the optimal sequence of HER2-targeted agents and the best drug combinations to use, as well as the recognition of primary and acquired drug resistance. In this article, we review clinical data informing the effective management of HER2-positive MBC.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/secondary ; Female ; Humans ; Molecular Targeted Therapy ; Receptor, ErbB-2/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1067950-9
ISSN	0890-9091
ISSN	0890-9091
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Article ; Online: Prevalence of chemopreventive agent use among hospitalised women at high risk for breast cancer: a cross-sectional study.

Khaliq, Waseem / Jelovac, Danijela / Wright, Scott M

BMJ open

2016 Volume 6, Issue 11, Page(s) e012550

Abstract: Objective: To characterise the current usage of chemoprevention agents among hospitalised women who are at higher risk for breast cancer.: Study design: A cross-sectional study.: Setting: Academic hospital at Baltimore.: Participants: A bedside ...

Abstract	Objective: To characterise the current usage of chemoprevention agents among hospitalised women who are at higher risk for breast cancer. Study design: A cross-sectional study. Setting: Academic hospital at Baltimore. Participants: A bedside survey of 250 women aged 50-75 years was conducted who were cancer-free at the time of study enrolment and hospitalised to a general medicine service. Reproductive history, family history for breast cancer, chemopreventive agents use and medical comorbidities data was collected for all patients. χ Primary outcome measures: Prevalence of women at high risk for developing breast cancer (5-year Gail risk score ≥1.7) and their chemopreventive agent use. Results: Mean age for the study population was 61.5 years (SD 7.5), and mean 5-year Gail risk score was 1.67 (SD 0.88). A third of study population was at high risk for breast cancer. None of the high-risk women (0%) were taking chemoprevention for breast cancer risk reduction, and 23% were at very high risk with 5-year Gail score ≥3%. These women were not recognised as being high risk by their hospital providers and none were referred to the high-risk breast cancer clinics following discharge. Conclusions: Many hospitalised women are at high risk for breast cancer and we could not identify even a single woman who was using chemoprevention for risk reduction. Current chemoprevention guidelines may be falling short in their dissemination and implementation. Since women at high risk for breast cancer may only interface with the healthcare system at select points, all healthcare providers must be willing and able to do risk assessment. For those identified to be at high risk, providers must then either engage in chemopreventive counselling or refer patients to providers who are more comfortable working with patients on this critical decision.
MeSH term(s)	Academic Medical Centers ; Age Distribution ; Aged ; Anticarcinogenic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/epidemiology ; Chemoprevention/statistics & numerical data ; Comorbidity ; Cross-Sectional Studies ; Female ; Hospitalization ; Humans ; Maryland ; Middle Aged ; Risk Assessment ; Risk Reduction Behavior ; Severity of Illness Index ; Surveys and Questionnaires
Chemical Substances	Anticarcinogenic Agents
Language	English
Publishing date	2016-11-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2747269-3
ISSN	2044-6055 ; 2044-6055 ; 2053-3624
ISSN (online)	2044-6055
ISSN	2044-6055 ; 2053-3624
DOI	10.1136/bmjopen-2016-012550
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Article ; Online: Role of farletuzumab in epithelial ovarian carcinoma.

Jelovac, Danijela / Armstrong, Deborah K

Current pharmaceutical design

2012 Volume 18, Issue 25, Page(s) 3812–3815

Abstract: Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Standard treatment for EOC is surgical debulking followed by platinum-based chemotherapy. While the ... ...

Abstract	Epithelial ovarian cancer (EOC) is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Standard treatment for EOC is surgical debulking followed by platinum-based chemotherapy. While the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately relapse. The major focus of current clinical trials for treatment of recurrent ovarian cancer is the use of targeted biologic agents. Folate receptor alpha (FRα) is upregulated in majority of EOC and correlated with tumor stage and grade. It is hypothesized that the presence of overexpressed FRα correlates with the propagation rate of the tumors. FRα is largely absent from normal tissue, making it an attractive therapeutic target. Farletuzumab (MORAb-003), a humanized monoclonal antibody against FRα, has shown antitumor activity in preclinical xenograft models. A Phase 1 dose escalation study did not demonstrate dose-limiting toxicities, or severe adverse effects. A phase 2 efficacy and safety study of farletuzumab with carboplatin and taxane in patients with platinum-sensitive EOC in first relapse, have shown an improved response rate and time to progression compared with historical controls. Recently, preliminary safety data from a phase 1 trial reported that the combination of farletuzumab, carboplatin and PLD has an acceptable safety profile in patients with platinum- sensitive EOC following first or second relapse. Two randomized, double-blind, placebo-controlled Phase 3 studies with farletuzumab plus chemotherapy have been done. A trial of: farletuzumab with weekly paclitaxel in platinum-resistant EOC closed in December 2011 with full report pending. A second trial of farletuzumab with carboplatin and taxane in platinum-sensitive EOC in first relapse is slated to complete accrual in early 2012. Results from these trials will help define the role of farletuzumab in EOC.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Clinical Trials as Topic ; Female ; Humans ; Neoplasms, Glandular and Epithelial/drug therapy ; Ovarian Neoplasms/drug therapy
Chemical Substances	Antibodies, Monoclonal, Humanized ; farletuzumab (2O09BG0OWA)
Language	English
Publishing date	2012-04-21
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/138161212802002698
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Zs.A 4714: Show issues

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Article ; Online: The adjuvant treatment of HER2-positive breast cancer.

Jelovac, Danijela / Wolff, Antonio C

Current treatment options in oncology

2012 Volume 13, Issue 2, Page(s) 230–239

Abstract: Opinion statement: About 15-20% of patients with early stage breast cancer present with tumors that have overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) gene. Before 2005, these individuals had an increased risk of ...

Abstract	Opinion statement: About 15-20% of patients with early stage breast cancer present with tumors that have overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) gene. Before 2005, these individuals had an increased risk of recurrence and death, but since then their outcomes have substantially improved with the adoption in most countries of adjuvant trastuzumab as a standard component of therapy for HER2-positive early-stage breast cancer. Consequently, access to high-quality and accurate HER2 testing methods is critical to accurately determine HER2 status, guide treatment decisions, and ultimately improve clinical outcomes. In 2012, the humanized monoclonal anti-HER antibody trastuzumab was the only approved HER2-targeted therapy in the adjuvant setting. Data from the first generation of trials combining it with various chemotherapy regimens showed significant improvements in disease-free and overall survival (DFS/OS). Based on results from five randomized clinical trials, a trastuzumab-containing regimen for up to 1 year is now considered standard for all patients with HER2-positive tumors larger than 1 cm in size who would have fulfilled eligibility to those studies, and this recommendation is sometimes extended to patients with stage I tumors greater than 0.5 cm (T1b). Second generation adjuvant studies with other HER2-targeted agents like lapatinib and pertuzumab are ongoing, and newer drugs like T-DM1 and neratinib are being actively tested in the metastatic setting.
MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cardiotoxins ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Genes, erbB-2 ; Heart/drug effects ; Humans ; Lapatinib ; Quinazolines/therapeutic use ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/immunology ; Trastuzumab
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Cardiotoxins ; Quinazolines ; Lapatinib (0VUA21238F) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; pertuzumab (K16AIQ8CTM) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2012-03-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057351-0
ISSN	1534-6277 ; 1527-2729
ISSN (online)	1534-6277
ISSN	1527-2729
DOI	10.1007/s11864-012-0186-4
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Zs.A 5523: Show issues

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Article ; Online: Recent progress in the diagnosis and treatment of ovarian cancer.

Jelovac, Danijela / Armstrong, Deborah K

CA: a cancer journal for clinicians

2011 Volume 61, Issue 3, Page(s) 183–203

Abstract: Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study ... ...

Abstract	Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study and may lower stage at diagnosis but have not yet been shown to improve survival. Women who have inherited a deleterious mutation in the BRCA1 or BRCA2 gene and those with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have the highest risk of developing ovarian cancer but account for only approximately 10% of those with the disease. Other less common and less well-defined genetic syndromes may increase the risk of ovarian cancer, but their contribution to genetic risk is small. A clear etiology for sporadic ovarian cancer has not been identified, but risk is affected by reproductive and hormonal factors. Surgery has a unique role in ovarian cancer, as it is used not only for diagnosis and staging but also therapeutically, even in patients with widely disseminated, advanced disease. Ovarian cancer is highly sensitive to chemotherapy drugs, particularly the platinum agents, and most patients will attain a remission with initial treatment. Recent advances in the delivery of chemotherapy using the intraperitoneal route have further improved survival after initial therapy. Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence. Chemotherapy for recurrent disease includes platinum-based, multiagent regimens for women whose disease recurs more than 6 to 12 months after the completion of initial therapy and sequential single agents for those whose disease recurs earlier. New targeted biologic agents, particularly those involved with the vascular endothelial growth factor pathway and those targeting the poly (ADP-ribose) polymerase (PARP) enzyme, hold great promise for improving the outcome of ovarian cancer.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Early Detection of Cancer/methods ; Female ; Genetic Predisposition to Disease ; Humans ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial/diagnosis ; Neoplasms, Glandular and Epithelial/genetics ; Neoplasms, Glandular and Epithelial/therapy ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/therapy ; Risk Factors ; Treatment Outcome
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2011-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	603553-x
ISSN	1542-4863 ; 0007-9235
ISSN (online)	1542-4863
ISSN	0007-9235
DOI	10.3322/caac.20113
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Zs.B 100: Show issues

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Article ; Online: The effect of 1-day multidisciplinary clinic on breast cancer treatment.

Akhtar, Zohaib / Stearns, Vered / Cartwright, Paul / Blackford, Amanda L / Prasath, Vishnu / Klein, Catherine / Jelovac, Danijela / Asrari, Fariba / Habibi, Mehran

Breast cancer research and treatment

2020 Volume 182, Issue 3, Page(s) 623–629

Abstract: Purpose: A delay in breast cancer treatment is associated with inferior survival outcomes; however, no clear guidelines exist defining the appropriate time frame from diagnosis to definitive treatment of breast cancer. A multidisciplinary approach for ... ...

Abstract	Purpose: A delay in breast cancer treatment is associated with inferior survival outcomes; however, no clear guidelines exist defining the appropriate time frame from diagnosis to definitive treatment of breast cancer. A multidisciplinary approach for breast cancer treatment can minimize the time from diagnosis to first treatment. We hypothesized single-day multidisciplinary clinic (MDC) may accelerate the time to first treatment on complex breast cancer cases at our institution. Methods: We identified patients who were treated at Johns Hopkins for stage II or III breast cancer, who were at least 18 years of age, and were seen in a new single-day MDC with coordination between two or three specialties or by specialists from varying disciplines on different days (IDC). Patients who initiated treatment between May 2015 (initiation of MDC clinic) and December 2017 were included in our study. Results: A total of 296 patient records were reviewed independently. The mean (SD) patient age was 55 (13) years. The median time to first neoadjuvant chemotherapy (NACT) was significantly reduced for patients seen in the MDC (12.7 days), compared to those seen at the IDC (24.4 days, logrank p < 0.001). The median time to definitive surgery was similar between groups (31 and 32 days for the MDC and IDC cohorts, respectively). Conclusions: A single-day MDC visit is associated with a reduced time from diagnosis to NACT. Further studies are needed to determine if a shorter interval can improve the management and the outcome of complex breast cancer cases.
MeSH term(s)	Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Delivery of Health Care/methods ; Delivery of Health Care/standards ; Female ; Follow-Up Studies ; Humans ; Interdisciplinary Communication ; Middle Aged ; Neoadjuvant Therapy ; Outcome Assessment, Health Care ; Patient Care Team/organization & administration ; Prognosis ; Quality Improvement ; Retrospective Studies ; Survival Rate ; Time-to-Treatment
Language	English
Publishing date	2020-06-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-020-05721-3
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Zs.A 1655: Show issues

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Article: Intraperitoneal treatment in ovarian cancer: the gynecologic oncology group perspective in 2012.

Armstrong, Deborah K / Fujiwara, Keiichi / Jelovac, Danijela

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2014 , Page(s) 345–348

Abstract: The peritoneal cavity is the major site of disease in ovarian cancer. The peritoneal predominance of disease provides a rationale for administration of chemotherapy within the peritoneal cavity. Intraperitoneal (IP) chemotherapy for ovarian cancer has ... ...

Abstract	The peritoneal cavity is the major site of disease in ovarian cancer. The peritoneal predominance of disease provides a rationale for administration of chemotherapy within the peritoneal cavity. Intraperitoneal (IP) chemotherapy for ovarian cancer has been studied rigorously for more than 30 years and has been reproducibly shown to improve the survival of patients with ovarian cancer. Three large randomized trials of IP compared with intravenous (IV) therapy have demonstrated statistically significant improvement in clinical outcome measures. Despite this, the IP approach has not gained widespread acceptance in the treatment of ovarian cancer. Here, we review reported, recently completed, and ongoing trials of IP therapy in ovarian cancer including attempts to improve the tolerability and acceptance of this proven approach.
Language	English
Publishing date	2014-01-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.14694/EdBook_AM.2012.32.345
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Article ; Online: PTEN promoter silencing and Cowden syndrome: the role of epigenetic regulation of KILLIN.

Jelovac, Danijela / Park, Ben Ho

JAMA

2010 Volume 304, Issue 24, Page(s) 2744–2745

MeSH term(s)	DNA Methylation ; Gene Silencing ; Genetic Predisposition to Disease ; Genetic Testing ; Germ-Line Mutation ; Hamartoma Syndrome, Multiple/complications ; Hamartoma Syndrome, Multiple/genetics ; Humans ; Neoplasms/complications ; Neoplasms/genetics ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	KLLN protein, human ; Tumor Suppressor Proteins ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2010-11-09
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2010.1863
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Article ; Online: Emerging immunotherapies in ovarian cancer.

Ojalvo, Laureen S / Nichols, Paige E / Jelovac, Danijela / Emens, Leisha A

Discovery medicine

2015 Volume 20, Issue 109, Page(s) 97–109

Abstract: Despite a global effort to significantly reduce mortality, ovarian cancer remains the fifth leading cause of cancer death among American women, and five-year survival rates remain discouragingly low at 45%. Novel therapies are urgently needed. Notably, ... ...

Abstract	Despite a global effort to significantly reduce mortality, ovarian cancer remains the fifth leading cause of cancer death among American women, and five-year survival rates remain discouragingly low at 45%. Novel therapies are urgently needed. Notably, higher infiltration of activated immune cells into the tumor microenvironment correlates with improved ovarian cancer survival, suggesting that promoting their activity could favorably impact clinical outcomes. Immunotherapy has recently demonstrated impressive clinical benefit in a variety of solid tumors. Immunotherapy strategies tested in ovarian cancer include vaccines, adoptive T cell therapy, and immune checkpoint blockade. Ultimately, a combination immunotherapy approach that integrates immunotherapy with other cancer treatment modalities in additive or synergistic ways will most effectively improve survival.
MeSH term(s)	Antibodies, Monoclonal/chemistry ; Antigens, Neoplasm/chemistry ; Antineoplastic Agents/chemistry ; B7-H1 Antigen/chemistry ; Cancer Vaccines/chemistry ; Clinical Trials as Topic ; Dendritic Cells/cytology ; Epitopes/chemistry ; Female ; Humans ; Immune System ; Immunotherapy/methods ; Immunotherapy/trends ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/therapy ; T-Lymphocytes/immunology ; Treatment Outcome ; Tumor Microenvironment ; United States
Chemical Substances	Antibodies, Monoclonal ; Antigens, Neoplasm ; Antineoplastic Agents ; B7-H1 Antigen ; CD274 protein, human ; Cancer Vaccines ; Epitopes
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1944-7930
ISSN (online)	1944-7930
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Article ; Online: The ENGAGE study: evaluation of a conversational virtual agent that provides tailored pre-test genetic education to cancer patients.

Journal of cancer survivorship : research and practice

2023

Abstract: Purpose: Novel approaches are needed to ensure all patients with cancer have access to quality genetic education before genetic testing to enable informed treatment decisions. The purpose of this study was to test the use of an artificial intelligence ( ... ...

Abstract	Purpose: Novel approaches are needed to ensure all patients with cancer have access to quality genetic education before genetic testing to enable informed treatment decisions. The purpose of this study was to test the use of an artificial intelligence (AI) intervention for the delivery of genetic education by non-genetic providers to patients with cancer undergoing active treatment. Methods: A conversational AI-based application was developed on the HealthFAX platform to provide tailored genetic education to patients with cancer and tested at Johns Hopkins Hospital between April 2021 and Feb 2022. Patients' responses around the adoption, use, and experience of the AI application were assessed. Results: Out of 64 individuals who consented to the study, 51 accessed the tool. The responding participants had a mean age of 61 years (ranging from 30-90 years) with 39 individuals undergoing active treatment for breast cancer and 12 for advanced prostate cancer. All patients chose to complete the tool at home. The median time between study enrollment and AI application initiation was 1 day, and the median time to complete the application was 24 min. All participants in their survey responses felt that the tool was secure, easy to use, liked the convenience of viewing it at home, and felt it provided valuable information. Eighteen percent of participants viewed the application with a family member. Ninety-eight percent of the participants completed their genetic education prior to receiving their test results. In 16%, a pathogenic variant was identified. Conclusions: The 51 patients who adopted the AI application were highly satisfied with its usability and convenience. Our results support the continued evaluation of this cost-effective AI application in a large-scale study. Implications for cancer survivors: Tailored pre-test genetic education can be successfully delivered to patients with cancer undergoing active treatment via an AI application at their convenience.
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2388888-X
ISSN	1932-2267 ; 1932-2259
ISSN (online)	1932-2267
ISSN	1932-2259
DOI	10.1007/s11764-023-01495-x
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