Updates in the Treatment of Early-stage HR+ Breast Cancer

EP: 1.The Evolution of the Breast Cancer Treatment Landscape

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EP: 2.Updates in the Treatment of Early-stage HR+ Breast Cancer

EP: 3.Novel Agents in the Adjuvant Setting: PARP Inhibitors

EP: 4.Clinical Implications of SERENA-2 Trial Data

EP: 5.Recent Updates for the Advanced HR+ Breast Cancer Setting

EP: 6.Key Takeaways from Clinical Trials of Trastuzumab Deruxtecan in Different Populations

EP: 7.Unmet Needs for Patients with HER2+ Breast Cancer with Brain Metastases

EP: 8.The Emerging State of HER2-low Breast Cancer

EP: 9.Trastuzumab Deruxtecan in the Neoadjuvant Setting

Dr. Ian Krop: So, kind of keeping with this theme of how we personalize therapy, we had in the adjuvant setting, we had this - I thought it was an interesting analysis of the SOFT data, speaking of ovarian suppression. In terms of looking at this genomic marker, the breast cancer index, which looks at two genes that have been associated with response to endocrine therapy, also looking at molecular grade, and also looking at some clinical staging mark- parameters, you know. They look at the SOFT data set and apply their breast cancer index to that data to try to identify patients who would or would not benefit from the ovarian suppression, and, you know, they saw, what I thought was interesting, and also surprising, that in their breast- in their BCI- I hope I remember this correctly. In their BCI low group, they saw the ovarian suppression benefit, whereas, in their BCI high, they did not, which again, is a little counterintuitive, since it's the BCI high that benefited from late adjuvant endocrine therapy, but, you know- I thought it was interesting. I don't know what your take on those data was.

Dr. Charles Geyer: Yeah. No, I mean, it's just that we continue to try to find the- a consistent theme, and I just think it all points to these uncertainties and the need to fill in these unknowns with the disease, because I agree. That is counterintuitive what you'd have thought, and then there's always when you break out the really young patients, 35, particularly from those 40 and above, we see- we see differences, so- but, you know, I think the indices for the- for late effects and things are a little bit different than what we're trying to focus on with these genomic markers, which are really more about the- what goes on in that first five years.

Dr. Ian Krop: Yeah. Yeah. So, before we kind of move on from that- from the kind of- from those endocrine therapy questions, we did get data from- from RxPONDER, the node-positive trial on race and clinical outcomes, which, you know, I thought were very interesting. Again, taking advantage of this very large data set. There's been, you know, a number of studies that have suggested that patients- that black patients with breast cancer have a worse prognosis than white patients, and it's always been hard to kind of tease out what some of the underlying causes of that disparity. So, you know, we're left with this difference that in this, again, well-done study. Everybody gets the same medications. It's hard to kind of say that, you know, that it- this is not something that's- something that we really have to focus on, even when, you know when we control for a lot of things that normally we don't control for in the real world.

Dr. Charles Geyer: Yeah. I may also comment that the- when you actually look at the numbers, the black women on the responder actually had- did better in terms of acceptance to assignment and adherence, at least in the first year, so I thought that was interesting, and this was data that was very consistent with what the TAILORx investigators had reported in 2021. Basically, the- you know, the African American women had higher dis- recurrence rates, worst overall survival, and again, on that study, they just looked at the outputs from the genomic health assay and did not see differences in the recurrence scores, the ESR 1, DGR, or HER2, so this is kind of a theme, and it- it is showing up more and more that it looks like the real disparities along race, particularly black versus white women is in this ER positive, HER2 negative group, and not so much the higher grade triple negatives and HER2 positive, which I think is interesting. And we did see a poster presented by Joe Sparano's group looking at this interesting kind of anatomical construct, the T MEMS [ph] is what he calls them. It's a little bit to get your head around, but the basic idea is, when they've- when they've looked at tumors in patients who have had neoadjuvant therapy, African American versus European American, they do see that the African American populations have increased Tregs, macrophages, microvascular densities, cytokines, so a number of things that would suggest more aggressive disease. But they have also studied sort of an anatomic finding of seeing repetitive clusters of triads of cells consisting of tumor cells, macrophages, and endothelial cells that they call these doorways for T MEMS, hematogenous dissemination, and they've worked out a way to look at these, I guess using a little bit of assisted imaging, and so they looked at that, little under 200 patients. They had 96 African American, 87 European American patients, non-PCRs, and they did see that these high T MEM scores were associated with worse DRFS as an independent prognostic factor, seemed to be more pronounced in the ER-positive, HER2 negative cohort, and definitely associated with black race, so it's an interesting effort to really understand maybe some unique biology there that might need- ultimately need some thoughtful targeting to try to address these disparities in this group.