Exploring Endocrine Therapy Benefits in Breast Cancer Treatment

Naomi Dempsey, MD

Identifying patients with hormone receptor-positive, HER2-negative early breast cancer who will benefit from extended endocrine therapy beyond 5 years can present a challenge. Historically, decisions were based on clinical factors like tumor size, lymph node status, and tumor grade. However, this paradigm may be changing.

Naomi Dempsey, MD, presented a poster at the 2023 San Antonio Breast Cancer Symposium (SABCS) entitled “Correlative analysis of Breast Cancer Index with CTS5 for prediction of extended endocrine benefit in the BCI Registry study.” Dempsey’s research followed the evolving use of the Breast Cancer Index, a genomic assay providing both prognostic and predictive information. The study examined the correlation between classic clinical risk factors and the Breast Cancer Index's predictive ability for extended endocrine therapy benefit.

Notably, half of high-risk CTS5 patients were predicted to benefit from extended therapy, while the other half would not. These findings emphasize the importance of incorporating genomic assays like the Breast Cancer Index for more precise decisions on extended endocrine therapy, rather than relying solely on traditional clinical risk factors.

In an interview with Targeted OncologyTM, Dempsey, breast medical oncologist at the Miami Cancer Institute, Baptist Health South Florida , provides insight into her poster and the implications the findings present for clinicians and patients.

Targeted Oncology: Could you provide some background on the poster from SABCS?

Dempsey: Patients with hormone receptor-positive, HER2-negative early breast cancer have risk of late distant recurrence. As clinicians, we are always trying to determine who is that patient who's going to benefit from extended endocrine therapy beyond 5 years vs those who will not. Historically, that decision was made based on things like large tumor size, positive lymph nodes, [and] high tumor grade. In more recentrecent years, many clinicians have started using the Breast Cancer Index to help us make these decisions. The Breast Cancer Index is a genomic assay that gives both prognostic information regarding the risk of late recurrence, but also predictive information that tells us about whether or not an individual patient will benefit from extended endocrine therapy.

The idea behind this poster was actually seeing how well those classic clinical pathologic risk factors correlate with the Breast Cancer Index prediction of increased benefit from extended endocrine therapy. In order toTo do this, we looked at women in the Breast Cancer Index Registry study, which is a registry of women with early hormone receptor-positive, HER2-negative breast cancer who had undergone testing with the Breast Cancer Index and had received adjuvant endocrine therapy. We looked at some of these clinical risk factors in these women, as well as looking at their Breast Cancer Index information. In order to put together all of those risk factors, we used the clinical treatment score, abbreviated as CTS5, that gives the prognostic information regarding those clinical pathologic risk factors and comparative to the predictive portion of the Breast Cancer Index to see how well those correlated—meaning, can we just use these clinical risk factors like large tumor size, node positivity, [and] high grade to predict who will benefit from endocrine therapy?

The statistics we use to evaluate this is the Pearson correlation coefficient. When this correlation coefficient labeled r is equal to 1, that's a perfect positive correlation [and] 0 was no correlation whatsoever. When we looked at these 2 variables together, the correlation was 0.18, meaning verya very poor correlation between the CTS5 and the Breast Cancer Index predictive result. Interestingly, when we looked at the patients specifically who would have been considered high risk with the CTS5 score. , Aabout half of those patients were predicted by Breast Cancer Index to have a benefit from extended endocrine therapy, . Bbut fullyanother half would not have benefited from extended endocrine therapy.

While we're all very comfortable with using endocrine therapy, we know that there are ongoing side effects, particularly issues with bone density [and] cardiovascular effects. It’s really important to determine who's actually going to benefit from that extended endocrine therapy. When we put this all together, basically it shows that we really should be using genomic assays, such as Breast Cancer Index, to determine who to give extended endocrine therapy to rather than simply using clinical risk factors, such as large tumor and nodal status.

What are some of the implications of these findings?, How can these findings affect patient care?

Patients are generally comfortable with the idea of taking 5 years of adjuvant endocrine therapy. That is kind of considered the standard. But there are certain patients who will benefit from 10 years of endocrine therapy, and it's important to determine who those patients are. Nobody wants to be taking a medication that they don't need. Many women are going to experience side effects from endocrine therapy—the ones that are not dangerous, but are uncomfortable, such as hot flashes and joint pain, but also ones that maybe they don't feel, such as a decrease in their bone density or a very small increase in cardiovascular risk, which needs to be integrated into their overall cardiovascular risk. Even for the women at 5 years, who say, “I don't have any side [adverse] effects, I feel fine, why not go to 10 [years]?” There may be side [adverse] effects that they are having that they are not feeling. Thus, it's important to determine who will actually benefit. Whereas in the past, we all just kind of said, “Well, if you've got a positive lymph node, if you have a larger tumor, you should take 10 years of adjuvant endocrine therapy,.” tThe results from my poster really suggest that a more genomically directed approach. Using an assay such as Breast Cancer Index can help us to make sure that we're giving the right duration of therapy to the right patient.