Memorial Sloan Kettering Cancer Center New York, New York
Molecular Geneticist Director of the Gynecology DMT Research Laboratory Pathology and Laboratory Medicine
Understanding the genetic drivers of rare forms of breast cancer to improve the accuracy of diagnosis and to develop novel treatment approaches.
The molecular make-up and clinical behavior of rare subtypes of breast cancer are often distinct from those of more common subtypes. Little is known about rare “special types” of breast cancer which account for up to 25 percent of all invasive breast cancers. Dr. Weigelt’s research focuses on defining the genetic drivers that promote the growth of these rare cancers. In the current study, her team is investigating the basis for the aggressiveness and poor response to chemotherapy of a rare type of breast cancer called metaplastic breast cancer. She and her colleagues use cutting-edge technologies to characterize the cellular composition of the immune tumor microenvironment to understand how it may mediate treatment response in metaplastic breast cancers. The results of these studies have the potential to identify new molecular targets to tailor the treatment for these patients.
Dr. Weigelt and her team have previously shown that metaplastic breast cancers, a rare type of triple-negative breast have unique defects in the way the cancer cells repair their DNA which may be associated with its aggressiveness and resistance to PARP inhibitor therapies. They are conducting whole-genome sequencing of metaplastic breast cancers to determine if genetic alterations affecting non-coding regions of the genome could be drivers of metaplastic breast cancers. Additionally, her team will expand their analysis to include single cell RNA sequencing in combination with assessment of the spatial orientation of tumor immune cells in the microenvironment. Examination at the single cell level will help to define how metaplastic breast cancer cells originate, differentiate, become genetically unstable, and subsequently impact their microenvironment.
Dr. Weigelt’s team will continue to leverage cutting-edge techniques to determine the immune cells present in metaplastic breast cancers. These findings will be integrated with the genetic profiles of these tumors to provide a comprehensive characterization and insights on which patients with this aggressive disease are likely to benefit from immune therapy. In parallel studies, her team is determining if the genetic profiles of rare breast cancers differ according to ancestry. Dr. Weigelt hopes these studies will reveal the basis for the diversity of metaplastic breast cancers and their microenvironment and help to optimize the treatment for these patients.
Britta Weigelt, PhD, is a Molecular Geneticist and the Director of the Gynecology DMT Research Laboratory at Memorial Sloan Kettering Cancer Center in New York, USA. She received her PhD from the Netherlands Cancer Institute/ University of Amsterdam, The Netherlands, and undertook her postdoctoral training at Lawrence Berkeley National Laboratory, Berkeley, USA, and Cancer Research UK London Research Institute, London, UK.
Dr. Weigelt has a long-standing research interest in the refinement of the classification of breast cancers and the identification of novel drivers and potential therapeutic targets by bringing together traditional pathology tissue-based techniques with genomics, bioinformatics, functional genomics, and signal transduction studies. She was part of a team that identified and functionally validated pathognomonic somatic genetic alterations in special histologic types of breast cancers and other rare cancer types, which can be employed for their detection and classification, including PRKD1 E710D somatic mutations underpinning polymorphous adenocarcinoma, IDH2 hotspot mutations or TET2 inactivating mutations in conjunction with PI3K pathway gene alterations in tall cell carcinomas with reversed polarity of the breast, and the co-occurrence of HRAS Q61 hotspot mutations with PIK3CA or PIK3R1 somatic mutations in adenomyoepitheliomas of the breast.
Dr. Weigelt has published her findings in over 280 peer-reviewed articles and is an author of chapters of the World Health Organization Classification book series, including the one on Breast Tumors. She is also on the Editorial Board of the Journal of the National Cancer Institute, The Journal of Pathology, Modern Pathology, and the European Journal of Cancer.
2023
The Estée Lauder Companies’ North American Research & Development and Supply Chain Award
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