Somatic Gene Alterations Correlate With Resistance in Black Patients With Luminal Breast Tumors

Yael Simons, MD, discusses the study of somatic driver gene alterations in a consecutive series of luminal breast tumors in Black patients, which received an American Society of Clinical Oncology Merit Award.

Yael Simons, MD, a hematology/oncology fellow at the University of Illinois Cancer Center (UIC), discusses the study of somatic driver gene alterations in a consecutive series of luminal breast tumors in Black patients, which received an American Society of Clinical Oncology Merit Award.

According to Simons, 35 African American luminal breast cancer patients were included in the analysis, 26 of whom were untreated and 9 of whom had metastatic sites. In total, 60 somatic gene alterations were identified.

Analysis found that resistance was found at an equal frequency in both treated and untreated tumors. This is unusual as resistance is typically found in already treated tumors, as tumors develop resistances as a type of defense mechanism. This may help to explain some of the racial disparities seen in cancer care.

According to Simons, other institutions should make an effort to replicate these findings. Next steps should include figuring out why these mutations happen in the first place.

0:08 | We have a pretty diverse population at UIC, a pretty large African American population. So, we were able to identify 35 luminal breast tumors from African American patients, the majority of those were actually primary tumors or untreated tumors. So, about 26 were untreated and 9 were from metastatic sites. And then we ran next generation sequencing to identify DNA and RNA gene alterations. And then, with our findings, we actually then compared it to the largest publicly available data set the Cancer Genome Atlas, to see if our cohort showed similar findings to this larger database that's available to identify 60 somatic gene alterations in these 35 tumors.

0:54 | I think the most interesting finding that we saw was that there was a high frequency of alterations in genes that normally are associated with endocrine resistance. And specifically, we saw these, like I mentioned, in more primary tumors than in metastatic tumors. So, we normally associate endocrine resistance with recurrent tumors or tumors that have already received treatment. But we were seeing that there is pretty much an equal frequency in both the primary tumors and the metastatic sites or the tumors that had already been treated. So, this was a somewhat surprising finding, because usually, we see that the tumors develop these as defense mechanisms. And so, this potentially explains some of the racial disparities that we're seeing in survival.

1:48 | Like I mentioned, UIC has a pretty large African American population, and we were really able to identify 35 patients with luminal breast tumors, which is a pretty large sample size, actually, when you've been compared to the largest publicly available database, the Cancer Genome Atlas. I think it would be really great for other institutions to really take a look at their registry and see if they also have a large African American population to identify if they're seeing similar findings that to what we are seeing with this underground resistance and earlier, untreated tumors. And if we're able to confirm these findings across the board, then I think the next steps would really be to take a better look, why is this happening? Why are we seeing more aggressive disease? Why are we seeing untreated tumors developing these treatment resistance mechanisms? Because this obviously has large implications for the treatments that we're offering to our patients.

2:49 | UIC really does a great job of focusing our research on the patients that we see. So, we have a number of different research projects going towards looking at disparities in health care, and, you know, screening and the treatments and outcomes across the spectrum of all cancer types. And I think that's really where we're really focusing on trying to figure out what might be some of the barriers and changes and differences in outcomes in the patients that we see and hope that that can then be applied across the country or even you know, across the world and other places that see similar patient types that we do to really expand on the literature and to help you know, with treating the different types of patients that we see.