Early-Stage Breast Cancer Detection Using Orphan Non-coding RNAs

Our guest today is Dr Hani Goodarzi, an Associate Professor in the Department of Biochemistry & Biophysics and the Department of Urology at the University of California, San Francisco. Dr Goodarzi is here to discuss his poster, “Early-Stage Breast Cancer Detection Using Orphan Noncoding RNAs,” which was recently presented at the 2022 San Antonio Breast Cancer Symposium (SABCS).

IO Learning: Welcome to IOL Radio. I’m Ami Peltier, Managing Editor of IO Learning, a digital publication geared toward interventional oncologists and the news source for the symposium on Clinical Interventional Oncology. Today, I’m pleased to welcome Dr. Hani Goodarzi, an Associate Professor in the Department of Biochemistry & Biophysics and the Department of Urology at the University of California, San Francisco. Dr Goodarzi is here to discuss his poster, “Early-Stage Breast Cancer Detection Using Orphan Noncoding RNAs,” which was recently presented at the 2022 San Antonio Breast Cancer Symposium (SABCS). Welcome back, Dr Goodarzi. You were recently here to tell us about using this technology and its efficacy in colorectal cancer. Can you tell us a little bit about the purpose of the current study in breast cancer?

Hani Goodarzi: So, to answer that, I want to first take a step back and talk a little bit about our version of a small noncoding RNAs that we've been studying. They're called orphan noncoding RNAs. These are specifically expressed in cancer cells. We actually originally discovered them in the context of breast cancer, but now we have expanded the annotations of oncRNAs across many human cancers as well.

What we had done initially, in our first publication, which was a Nature Medicine paper that came out in 2018, was basically a description of oncRNAs, specifically in breast cancer. And in that context, we had basically looked at existing data sets, to show that these oncRNAs are not only expressed in breast cancer cells, but also a fraction of them are secreted. So, we leveraged that finding to then do a retrospective study, the I-SPY trial here at UCSF, which is a breast cancer adaptive trial in new adjuvant therapies to look at minimal residual disease pre and post therapy.

So, that was a study that we did a few years ago, and the results of it were published at SABCS a few years earlier, and basically showed that we do see a relationship between oncRNA content in the blood of patients and tumor burden.

What remained to be answered was the question of whether we can actually leverage oncRNAs for early detection of breast cancer as well, because it's one of the indications that it has been very difficult, based on DNA modalities, to achieve enough sensitivity for early detection. So really this study was designed as a retrospective study to answer that question of whether we can use oncRNAs to detect breast cancer in earlier stages basically.

IO Learning: So that was more of a validation study for breast cancer?

Hani Goodarzi: Exactly. It was designed specifically to answer the question of whether we can use oncRNAs to detect breast cancer early, when it's small.

IO Learning: Can you tell us a little bit more about the study endpoints and patient population? Why did you choose these particular tumor types and size ranges for this study?

Hani Goodarzi: Absolutely. So as I mentioned, this study was really designed to skew toward earlier stages in smaller tumors. So, because this is a retrospective trial, we could really pick how we wanted to stratify patients across different stages. So among the 96 or so patients that are studied here, and on the reference side, we have 95 age-matched, control-samples as well. Forty-five of them are basically stage 1 and about the same number are T1, which is the smallest tumor size. So as I mentioned, the goal here was really to skew the samples toward lower stages and earlier disease to be able to answer the question of how early we can actually detect oncRNAs, in the blood of patients.

IO Learning: Briefly outline your results. Did anything surprise you about them?

Hani Goodarzi: Basically, what came out of this study was that once we had trained our classifiers, we observed that we can detect cancer quite early, so our sensitivity was about 80% across the board, starting from stage 1 tumors. So this was actually surprising. We expected kind of like a decay towards earlier stages, which is what other DNA modalities had seen, but we see very strong performance really even from early stages, which is both a delight but also surprising.

IO Learning: Is it possible that this would become a routine part of preventative care, perhaps even replacing a mammogram in the future? Do you feel it has that potential?

Hani Goodarzi: We certainly hope so. I think a mammogram also has its own pitfalls, especially in cases of women who have dense breasts, for example, so there is certainly an opportunity to be able to accompany that as some sort of a screening modality. However, I think the way that I look at it as a scientist is that breast cancer is a special case, in that there is really an inflection point between earlier stages and later stages, because it's extremely operable as a cancer, so if you find this disease in the early stages—stage 1 and 2—your prognosis is extremely strong. So, it's a kind of a cancer that we know how to treat, it's very clinically actionable, so early detection is actually extremely important.

But the flip side of it is that is what we really hope to achieve with oncRNAs is to go beyond simply detecting cancer, but also being able to tell something about the biology of that cancer, and really peer into long-term risk of that cancer as well. I think ultimately that's why biopsies are useful. It's not that they only tell you whether there is a disease or not, but they also tell you what to do about that disease, and whether anything needs to be done about that disease. Now, liquid biopsies also need to get there, basically. They also need to not just tell you that there is an underlying tumor, but also whether you need to do anything, as a clinician, about that tumor, and if you need to do anything, what kind of steps are available to you?

IO Learning: Can you tell us a little bit about how this technology might affect the clinical practice of a typical interventional oncologist?

Hani Goodarzi: So, I think in the previous question, I kind of answered some components of this. I think there are multiple places that you can take advantage of oncRNAs in the clinic, which we have actually been exploring. One, as I mentioned in is in the context of, minimal residual disease detection, kind of basically risk of stratifying patients, post therapy and post surgery, for the need for additional therapies, if the tumor clearance was not complete, and whether there was evidence of tumor in the body, even after surgery. The other side of it, as I mentioned, is earlier detection of stage 1 and 2 breast cancers, which are extremely operable, especially for women who struggle with mammogram for a variety of reasons.

IO Learning: How has the audience responded now that you’ve shared these results at a few different clinical meetings?

Hani Goodarzi: I think that over time, broadly, the world is being educated in real time about liquid biopsies. I think even in the span of 5, 6 years, we have gone from a world that was fairly skeptical and really didn't see broad utility in liquid biopsies in general, and I was certainly myself in that camp and I still am for certain types of applications. However, over the past few years we have seen the power of these technologies that allow us to do things that we couldn't imagine 5 or 6 years ago. And it's also very clear that, say, the National Cancer Institute also agrees and I think the next decade is the decade of screening modalities and liquid biopsies, and that really changes how we look at access to screening among our catchment area, different cancer centers, and how we can deliver this type of screening modality to the population in a safe and effective manner.

IO Learning: Can you tell us about any ongoing or potential future studies that you haven't already covered?

Hani Goodarzi: So as you mentioned, we have talked about our breast cancer and colon cancer work. Ultimately, we are doing these validation studies across multiple cancers. As I mentioned, we had first annotated oncRNAs in the context of breast cancer, so this study was really kind of going back home to early days of oncRNAs, but we have since expanded an annotations of oncRNAs across human cancers, about 30 or so. We are setting up, at least for some cancers, these kinds of validation studies to really get a feel for which cancers can take advantage of oncRNAs for early detection. We have published a couple of these, and hopefully, there will be a few more to come in the near future as well.

IO Learning: Do you have any final thoughts or anything else you'd like to add on the topic?

Hani Goodarzi: I think, again, I want to emphasize that I think that the next decade is when we get to really realize the power of biopsies, and be able to re-think our clinical strategies around them, both in the context of minimal residual disease detection, survivorship, but also early detection for certain cancers, where there are clear, actionable benefits to them.

IO Learning: Fantastic. Well, Dr. Goodarzi, thank you so much for being here with us.

Hani Goodarzi: My pleasure. Thanks for having me.

IO Learning: That wraps up another episode of IOL Radio. To listen to more conversations on topics of interest to interventional oncologist, please visit the podcast page at iolearning.com.