Real-World Data Reveals Opportunities to Improve HER2-Low Metastatic Breast Cancer Care

In this interview with Pharmacy Times, Jessica Paulus, ScD, Vice President, Real-World Research, Ontada, discusses emerging trends in HER2-low metastatic breast cancer care and the growing role of real-world evidence in improving treatment decision-making. Paulus explains that while HER2 testing is now nearly universal in breast cancer care, variability still exists in how clinicians interpret HER2-low results and apply guideline-concordant therapies in community oncology settings. She highlights research showing that targeted educational interventions—including peer-led podcasts and embedded electronic medical record tools—improved guideline-concordant HER2-low treatment rates from 61% to 72%.

Pharmacy Times: As HER2-low therapies become more integrated into breast cancer care, what trends are you seeing in real-world adoption across community oncology practices?

Jessica Paulus, ScD: I think what’s really interesting here about HER2-low is that it’s more about a classification shift that builds on something clinicians were already doing. At this point, HER2 testing is essentially universal in breast cancer, thankfully. Adoption is not about introducing a new test or making sure that providers are using the HER2 test, because they are. It’s more about changing, or supporting, how clinicians interpret results from HER2 tests that were previously considered negative.

In the real world, we’re seeing that translation happen a bit unevenly. There are definitely clear signals that some clinicians are incorporating HER2-low–directed therapies very quickly, especially in the metastatic setting, but there is still some heterogeneity, or variation, in how consistently these patients are identified and then treated according to updated guidelines.

The opportunity we had here was not about testing access per se; it was more about clinical interpretation and integration into treatment pathways. This is exactly where real-world data can add value by showing where aspects of practice are aligning with evidence, particularly with guidelines, and where gaps still exist at scale.

Pharmacy Times: Your research focuses on educational initiatives to improve HER2-low therapy use. What are some of the biggest knowledge or implementation gaps that still exist among providers treating metastatic breast cancer?

Paulus: Yeah, so the biggest gap we’re seeing is, again, not about testing itself, but about how those results are translated into treatment decisions. In our study, which leveraged data from the US Oncology Network, HER2 testing rates were already extremely high, but there was still meaningful variation in whether patients with HER2-low disease were receiving guideline-concordant therapy.

This suggests the challenge is less about awareness and more about application—understanding which patients are eligible, when to use the therapies, and how they fit into what is admittedly an increasingly complex and highly dynamic treatment landscape.

What was very encouraging is that we saw targeted and highly embedded educational physician supports, especially those that are data driven, made a measurable difference. We used short-form peer education in a podcast, as well as point-of-care tools embedded in the EMR. These interventions resulted in a clinically significant improvement in guideline-concordant care in the HER2-low space, increasing from about 61% to 72%. That is a huge change over a short period of time and a clinically significant public health difference.

I think these kinds of supports can bridge that last mile between guidelines and real-world practice in a way that is very practical for busy clinicians.

Pharmacy Times: In evaluating distress thermometer scores among patients with metastatic breast cancer, were there any findings that highlighted the connection between emotional distress and treatment outcomes or care utilization?

Paulus: One of the most important findings from this work is that distress, the distress thermometer, and its component domain measures were not just descriptive measures. We found that they were actually prognostic. In particular, we saw that higher distress scores were associated with worse overall survival, even after adjusting for recognized clinical factors. This suggests that patient-reported distress is capturing something very meaningful about the underlying risk.

One of the other key takeaways is that it’s not just the overall distress thermometer score that matters, but what is driving that distress. We saw that, in metastatic breast cancer, physical concerns—things like symptoms and treatment-related burdens—were particularly important.

That shifts the way we might think about distress screening from something that is nice to have, or that can facilitate certain conversations, to something that can meaningfully inform how we risk stratify patients, as well as how we triage or prioritize supportive care interventions.

Pharmacy Times: How can real-world evidence help clinicians better understand the day-to-day experiences of patients with metastatic breast cancer and ultimately improve personalized care strategies?

Paulus: Again, I think both of these studies, or projects, are important demonstrations of how real-world evidence can provide real-time visibility into the patient experience. This is something that is usually missing from clinical trials.

In one of these cases, we saw that integrating the distress thermometer into the EHR allows us to systematically capture patient-reported burden, including emotional, physical, social, and spiritual concerns, as a real part of routine care. That is so important because it allows us to move beyond just tracking treatments, clinical symptoms, and outcomes and better understand how patients are doing on a day-to-day basis.

From a clinical perspective, that opens the door to much more personalized care by identifying patients who might need additional support, intervening on those gaps earlier, and tailoring care and supportive measures not just to disease characteristics but to the patient’s lived experience as well.