Medicine and Health Sciences Commons^™

Can Novel Technologies Improve Breast Conserving Surgery?, Brian W. Pogue

Dartmouth Scholarship

The practice of breast conserving surgery has been transformative for management of women’s breast cancer, and yet the current practice remains in a situation where approximately one-third of all patients have incomplete surgical resection. This is measured by the finding of clear margins on the surgical specimen, as measured by pathology sampling. This is a very active area of professional debate and research study, and the solutions are not as obvious as one might guess. Still, reviews of the status of the field suggest that technical solutions should be available to help mitigate this issue, and the tools for molecular …

Addition Of T2-Guided Optical Tomography Improves Noncontrast Breast Magnetic Resonance Imaging Diagnosis., Jinchao Feng, Junqing Xu, Shudong Jiang, Hong Yin, Yan Zhao, Jiang Gui, Ke Wang, Xiuhua Lv, Fang Ren, Brian W. Pogue, Keith D. Paulsen

Dartmouth Scholarship

BACKGROUND:

While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) is recognized as the most sensitive examination for breast cancer detection, it has a substantial false positive rate and gadolinium (Gd) contrast agents are not universally well tolerated. As a result, alternatives to diagnosing breast cancer based on endogenous contrast are of growing interest. In this study, endogenous near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to explore whether the combined imaging modality, which does not require contrast injection or involve ionizing radiation, can achieve acceptable diagnostic performance.

METHODS:

Twenty-four subjects-16 with pathologically confirmed malignancy and 8 with benign …

Optimizing Fresh Specimen Staining For Rapid Identification Of Tumor Biomarkers During Surgery., Connor W. Barth, Jasmin M. Schaefer, Vincent M. Rossi, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Rationale: Positive margin status due to incomplete removal of tumor tissue during breast conserving surgery (BCS) is a prevalent diagnosis usually requiring a second surgical procedure. These follow-up procedures increase the risk of morbidity and delay the use of adjuvant therapy; thus, significant efforts are underway to develop new intraoperative strategies for margin assessment to eliminate re-excision procedures. One strategy under development uses topical application of dual probe staining and a fluorescence imaging strategy termed dual probe difference specimen imaging (DDSI). DDSI uses a receptor-targeted fluorescent probe and an untargeted, spectrally-distinct fluorescent companion imaging agent topically applied to fresh resected …

The E2f4 Prognostic Signature Predicts Pathological Response To Neoadjuvant Chemotherapy In Breast Cancer Patients, Kenneth M. K. Mark, Frederick S. Varn, Matthew H. Ung, Feng Qian, Chao Cheng

Dartmouth Scholarship

Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in …

Cis-Eqtl-Based Trans-Ethnic Meta-Analysis Reveals Novel Genes Associated With Breast Cancer Risk, Joshua Hoffman, Rebecca Graff, Nima Emami, Caroline Tai, Michael Passarelli

Dartmouth Scholarship

Breast cancer is the most common solid organ malignancy and the most frequent cause of cancer death among women worldwide. Previous research has yielded insights into its genetic etiology, but there remains a gap in the understanding of genetic factors that contribute to risk, and particularly in the biological mechanisms by which genetic variation modulates risk. The National Cancer Institute's "Up for a Challenge" (U4C) competition provided an opportunity to further elucidate the genetic basis of the disease. Our group leveraged the seven datasets made available by the U4C organizers and data from the publicly available UK Biobank cohort to …

Willingness To Test For Brca1/2 In High Risk Women: Influenced By Risk Perception And Family Experience, Rather Than By Objective Or Subjective Numeracy?, Talya Miron-Shatz, Yaniv Hanoch, Benjamin A. Katz, Glen M. Doniger, Elissa M. Ozanne

Dartmouth Scholarship

Genetic testing for breast and ovarian cancer can help target prevention programs, and possibly reduce morbidity and mortality. A positive result of BRCA1/2 is a substantial risk factor for breast and ovarian cancer, and its detection often leads to risk reduction interventions such as increased screening, prophylactic mastectomy and oophorectomy. We examined predictors of the decision to undergo cancer related genetic testing: perceived risk, family risk of breast or ovarian cancer, and numeracy as predictors of the decision to test among women at high risk of breast cancer. Stepwise regression analysis of survey responses from 459 women registered in the …

Integrative Analysis Of Survival-Associated Gene Sets In Breast Cancer, Frederick S. Varn, Matthew H. Ung, Shao Ke Lou, Chao Cheng

Dartmouth Scholarship

Patient gene expression information has recently become a clinical feature used to evaluate breast cancer prognosis. The emergence of prognostic gene sets that take advantage of these data has led to a rich library of information that can be used to characterize the molecular nature of a patient’s cancer. Identifying robust gene sets that are consistently predictive of a patient’s clinical outcome has become one of the main challenges in the field. We inputted our previously established BASE algorithm with patient gene expression data and gene sets from MSigDB to develop the gene set activity score (GSAS), a metric that …

Genome-Wide Dna Methylation Profiles In Progression To In Situ And Invasive Carcinoma Of The Breast With Impact On Gene Transcription And Prognosis, Thomas Fleischer, Arnoldo Frigessi, Kevin C. Johnson, Hege Edvardsen, Nizar Touleimat, Jovana Klajic, Margit Lh Riis, Vilde D. Haakensen, Fredrik Wärnberg, Bjørn Naume, Åslaug Helland, Anne-Lise Børresen-Dale, Jörg Tost, Brock C. Christensen, Vessela N. Kristensen

Dartmouth Scholarship

Background: Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results: We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals …

The Influence Of Race/Ethnicity And Place Of Service On Breast Reconstruction For Medicare Beneficiaries With Mastectomy, Tracy Onega, Julie Weiss, Karla Kerlikowske, Karen Wernli

Dartmouth Scholarship

Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic …

Subjective But Not Objective Numeracy Influences Willingness To Pay For Brca1/2 Genetic Testing, Talya Miron-Shatz, Yaniv Hanoch, Glen Doniger, Zehra Omer, Elissa M. Ozanne

Dartmouth Scholarship

A positive test result for BRCA1/2 gene mutation is a substantial risk factor for breast and ovarian cancer. However, testing is not always covered by insurance, even for high risk women. Variables affecting willingness to pay (WTP) have implications for clinic-based and direct-to-consumer testing. The relative impact of objective and subjective numeracy on WTP, in the context of worry, perceived risk (of having the mutation and developing breast cancer) and family history, was examined in 299 high-risk women, not previously tested for BRCA1/2. Objective and subjective numeracy correlated positively with one another, yet only subjective numeracy correlated (positively) with …