Ana Garrido-Castro, MD

Ana Garrido-Castro, MD

Dana-Farber Cancer Institute

Choosing the best treatments for metastatic breast cancer depends increasingly on molecular features, such as tumor subtype. Patients with hormone receptor-positive/HER2-negative breast cancer are typically treated initially with hormonal therapies, and then subsequently with chemotherapy once hormonal therapy loses its effectiveness. Loss of hormone receptor expression has been described as a mechanism of resistance to hormonal therapy. When this occurs, tumors become hormone receptor-negative and HER2-negative, i.e. triple-negative. It is unknown whether cancers that start out hormone receptor-positive and then become triple-negative (called “subtype switch”) are different than those that remain triple-negative throughout a patient’s disease course. Since treatments depend so heavily on tumor subtype, answering this question could have an immediate impact on patient care.

Metastatic triple-negative breast cancer (mTNBC) remains a clinically unmet need, with a highly aggressive clinical course and shorter average survival compared to patients with other subtypes of metastatic breast cancer. Patients whose tumors are initially hormone receptor-positive/HER2-negative and then lose hormone receptor expression (i.e. become triple-negative) are typically eligible for clinical trials and standard-of-care therapies focused on mTNBC. However, comparison of tumor biology and clinical outcomes in patients whose tumors are always triple-negative and those that “switch subtype” has not been studied in detail. Preliminary results from tumor DNA analysis presented by Dr. Garrido-Castro at the 2018 San Antonio Breast Cancer Symposium suggest that primary hormone receptor-positive tumors in patients who later developed mTNBC have similar mutation and gene copy number alterations as primary triple-negative tumors.

In addition, hormone receptor-positive breast cancers are generally considered ̈cold ̈ tumors, characterized by decreased immune cell infiltration and low responsiveness to immunotherapy. It is unclear if hormone receptor loss may induce conversion to an immunologically ̈hot ̈ tumor that is more susceptible to immunotherapy. This would have therapeutic implications given recent evidence supporting the combination of immune checkpoint inhibition and chemotherapy as first-line therapy in patients with mTNBC.

As a Terri Brodeur Breast Cancer Foundation Grant recipient, Dr. Garrido-Castro aims to: a) identify genomic profiles and characteristics of the tumor microenvironment associated with hormone receptor loss, and b) compare these features across tumors with different levels of hormone receptor expression. We hypothesize that primary hormone receptor-positive tumors in patients who later developed mTNBC harbor intrinsic genomic and immune profiles that are similar to primary triple-negative tumors. To test this, we will integrate cutting-edge technologies (i.e. RNA sequencing, multiplex immunofluorescence, assessment of tumor-infiltrating immune cells) to analyze tumor samples collected at Dana-Farber Cancer Institute and correlate these findings with already generated DNA sequencing data.

Dr. Garrido-Castro received her M.D. from Universidad Autónoma de Madrid (Madrid, Spain) and later completed her training in Medical Oncology at Vall d’Hebron University Hospital in Barcelona, Spain. She joined Dana-Farber Cancer Institute in July 2016 after being selected for the Advanced Fellowship in Breast Oncology Program and as a Research Fellow at Harvard Medical School. She recently joined the Faculty at the Dana-Farber Susan F. Smith Center for Women ́s Cancers and will be appointed Instructor in Medicine at Harvard Medical School.

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