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Lehmann’s Classification Refines our Understanding of Triple Negative Breast Cancer

Einstein’s theory of relativity, the Pythagorean theorem and Lehmann’s Refined Classification – what do these have in common? The first two are named to reflect the significant contributions made by the individuals responsible for their founding. In the world of breast cancer research, Lehmann’s Refined Classification may one day have a similar impact.

Dr. Brian Lehmann has dedicated his career to the study of triple-negative breast cancer (TNBC), an especially aggressive form of breast cancer with a poor survival rate. He began his studies while training in Dr. Jennifer Pietenpol’s laboratory at Vanderbilt University Medical Center in Nashville, TN. Dr. Pietenpol currently serves as Chief Scientific Advisor for Komen, and is considered a leading expert in TNBC.

Dr. Lehmann says, “TNBC is a challenge to treat because it is defined by the absence of, rather than the presence of,  estrogen receptor (ER), progesterone receptor (PR), and HER2. Therefore, the disease itself is not one disease but a collection of breast cancers that do not fit into well characterized subtypes.”

Under Dr. Pietenpol’s guidance and with funding from Komen, Dr. Lehmann published his work in the Journal of Clinical Investigation (JCI) and in PLOS One. He showed that TNBC can be organized into six subtypes:mesenchymal stem-like (MSL) immunomodulatory (IM), basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M) and luminal androgen receptor (LAR). He also demonstrated that certain subtypes are more responsive to treatment than others. The ability to distinguish distinct biological subtypes of TNBC could better inform clinical trial design and help identify new biomarkers and drug targets. It could also help guide treatment decisions for people and ultimately improve long-term survival.

Lehmann’s Refined Classification is a name ascribed to his findings and was coined by fellow Komen-funded investigators in a Clinical Cancer Research publication. This finding focused on evaluating the predictive value of Lehmann’s TNBC subtyping in people. This work validated Dr. Lehmann’s classification by showing that certain TNBC subtypes respond better or worse to chemotherapy. One of the major challenges facing people with TNBC is the inability to predict which patients will respond to standard chemotherapy. So, this work could have major implications in the clinic by guiding clinical  decisions to align people with treatments most likely to work for their subtype of disease.

Dr. Lehmann is driven by the desire to improve patients’ lives, expand the treatment options available and provide people and their health care providers with the most accurate information. His work holds a lot of promise in accomplishing these goals. Like many basic research scientists, who do not directly interact with patients, Dr. Lehmann thought it would be years before his discoveries directly impacted the life of a patient. However, his work made a clinical impact much earlier than expected.

One clinician used Dr. Lehmann’s TNBC subtype classification data (JCI publication above) to help a person with TNBC gain entry into a clinical trial after she was initially denied access to due to eligibility requirements. When asked about this, Dr. Lehmann said, “I strive to make sure my work will improve patient lives, knowing it could be years or decades before I see the clinical result. But, in this case, my research made a direct impact on the life of one patient and there is no better reward than that.”

In recognition for his dedication to breast cancer research and improving the lives of those facing TNBC, Dr. Lehmann was  named a 2019 Pink Tie Guy for the Komen Central Tennessee Affiliate.