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Determinants of Progression in Early Breast and Ovarian Cancer

Scientific Focus

Research efforts led by Jeffrey Marks, PhD, and E. Shelley Hwang, MD, MPH, focus on the earliest stages of breast cancer. Working at the center of multi-institutional and multi-disciplinary projects on the disease, the Marks-Hwang laboratory studies the genetics, microenvironment, and evolution of early breast cancer. We are studying primary human ductal carcinoma in situ (DCIS) lesions that have not progressed to invasive cancer and comparing these to lesions that have progressed to invasive and metastatic disease. Our central hypothesis regarding progression is that principles of evolution applied to human cancer can help to predict which lesions should be aggressively treated from those that are indolent and unlikely to progress. 

To test this, we are pushing next-generation sequencing to the current technologic limits to derive broad exome-based DNA analysis to measure variant alleles and copy number changes that underlie the genetic and phenotypic heterogeneity of the disease. In parallel, we are also measuring parameters of the microenvironment as additional driving forces in tumor evolution. Our goal is to combine the most informative elements that define heterogeneity into a practical tool that can accurately predict the likelihood of progression. 

The lab has focused on highly multi-disciplinary projects incorporating quantitative, population, genetic, and behavioral approaches. Given the heterogeneity of human beings and the cancers that arise in them, it is essential to balance and validate insights gained from in vitro approaches and model systems with the actual primary disease states. Fully embracing this heterogeneity and complexity towards incorporating it into clinical practice constitutes the next major challenge our lab seeks to explore in cancer research. 

Dr. Marks is a Ph.D. basic/translational scientist who has investigated numerous aspects of breast and ovarian cancer since joining the faculty of the Department of Surgery in 1988. Dr. Hwang is a breast cancer surgeon and translational researcher who has been at Duke since 2011. These two investigators have common interests in studying cancer progression of DCIS, an increasingly common diagnosis that is not invasive at the time of presentation but carries a measurable risk of invasive progression. Treatment for this proliferative breast condition ranges from a watchful waiting approach to bilateral mastectomy. Therefore, in addition to the biologic relationship between DCIS and invasive cancer, the broad range of treatments that are considered appropriate makes this disease of great scientific interest and fundamental importance. The lab is highly interdisiciplinary and integrates scientific collaborators from UCSF, OHSU, Stanford University, USC, and member institutions of the TBCRC, a clinical trials translational research network.

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Jeffrey R. Marks, PhD

Shelley Hwang, MD, MPH

Lorraine King, PhD

Latest Publications

Narayanan, P. L., S. E. A. Raza, A. H. Hall, J. R. Marks, L. King, R. B. West, L. Hernandez, et al. “Unmasking the immune microecology of ductal carcinoma in situ with deep learning (Accepted).” In Npj Breast Cancer, Vol. 7, 2021.

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Korde, Larissa A., Mark R. Somerfield, Lisa A. Carey, Jennie R. Crews, Neelima Denduluri, E Shelley Hwang, Seema A. Khan, et al. “Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline.” Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 39, no. 13 (May 2021): 1485–1505.

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Grimm, Lars J., Benjamin Neely, Rui Hou, Vignesh Selvakumaran, Jay A. Baker, Sora C. Yoon, Sujata V. Ghate, et al. “Mixed-Methods Study to Predict Upstaging of DCIS to Invasive Disease on Mammography.” Ajr Am J Roentgenol 216, no. 4 (April 2021): 903–11.

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Tamirisa, Nina P., Yi Ren, Brittany M. Campbell, Samantha M. Thomas, Oluwadamilola M. Fayanju, Jennifer K. Plichta, Laura H. Rosenberger, et al. “Treatment Patterns and Outcomes of Women with Breast Cancer and Supraclavicular Nodal Metastases.” Annals of Surgical Oncology 28, no. 4 (April 2021): 2146–54.

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