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ASCO 2025 | Distinct genomic alterations in histomolecular invasive lobular carcinoma

Jason Mouabbi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on macroscale genomic features distinguishing histomolecular invasive lobular carcinoma (hmILC) from other breast cancer subtypes. The analysis highlights unique copy number variation patterns, lower frequency of homologous recombination deficiency, and higher tumor mutational burden and APOBEC activity in hmILC. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.

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Transcript

Yeah, so it’s important to define what lobular cancer is because the whole idea we’re trying to say is that lobular cancer is different than the most common breast cancer called invasive ductal carcinoma. So there have been a series of different posters at different meetings for the past three years that we’ve been doing and this is one of them, not the last one, one of them, that here we’re looking at macro scale, so big scale differences between lobular and ductal...

Yeah, so it’s important to define what lobular cancer is because the whole idea we’re trying to say is that lobular cancer is different than the most common breast cancer called invasive ductal carcinoma. So there have been a series of different posters at different meetings for the past three years that we’ve been doing and this is one of them, not the last one, one of them, that here we’re looking at macro scale, so big scale differences between lobular and ductal. And again, we see that there are different cancers. So if you look at copy number variations, there are different deletions, different amplifications seen in lobular cancer compared to ductal cancer, making them different cancers. If you look at the type of mutations they have, so for example, tumor mutation burden, it’s way higher in lobular cancer compared to ductal cancer. If we look at HRD signatures, so these are hereditary signatures, deficiencies. So if you look at that also, lobular cancers are different. And finally, and most important and very close to home is the APOBEC signature. So the APOBEC signature is a signature of aggressiveness. Those cancers are very aggressive. One in three lobular cancers have high APOBEC signature. Only one in five ductal cancers have that. So it’s a different cancer. It needs to be treated differently and have specific therapies tailored for it.

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