Using Recurrence Risk to Tailor Treatment in HR+/HER2- Breast Cancer

Ruta D. Rao, MD

In tailoring treatment to patients with early-stage hormone receptor (HR)—positive, HER2-negative breast cancer—be it through escalated or de-escalated approaches—the key factors to consider are the patient’s risk for recurrence, how well they’re tolerating the medication, and tumor biology, said Ruta D. Rao, MD.

“The most important thing we have to take into account is the patient,” said Rao. “The patient's risk of recurrence should inform our decision on how strongly we should advocate for a longer duration of therapy. Additionally, [we need to consider] how they’re tolerating the adverse events [associated with the treatment].”

After completing 5 years of adjuvant endocrine therapy, the data are inconclusive as to whether a patient should continue on treatment or stop therapy altogether. In both the ATLAS and aTTOm trials, patients who were randomized to receive an additional 5 years of tamoxifen experienced an absolute benefit in disease-free survival (DFS) versus placebo.

Conversely, more recent data from the IDEAL trial showed no DFS benefit in patients who were randomized to receive an additional 2.5 or 5 years of letrozole. However, a subgroup analysis suggested a benefit among women with node-positive disease who completed 5 years of letrozole.

The benefit of extending therapy has to be considered alongside the adverse events (AEs) that are associated with endocrine therapy, added Rao. Among the aromatase inhibitors (AIs), those AEs include a higher fracture rate.

Beyond treatment escalation, recurrence risk and genomic classifiers are also proving useful in guiding de-escalated treatment, said Rao. As reported in the MINDACT and TAILORx trials, women categorized as low-risk according to the MammaPrint 70-gene assay and those with an Oncotype DX recurrence score of 0 to 10 and 11 to 25 can most likely receive endocrine therapy alone versus in combination with chemotherapy.

“Previously, we used to give adjuvant chemotherapy to patients who had certain characteristics based on tumor size or lymph node status,” said Rao. “What we're learning now is that it may be the tumor biology that more likely predicts the risk of recurrence.”

OncLive: What studies have informed what is known about the optimal duration of endocrine therapy?

In an interview during the 2019 OncLive^® State of the Science Summit™ on Breast Cancer, Rao, an associate professor at Rush University Medical Center, highlighted the importance of determining risk for recurrence and its impact on conversations about extended adjuvant endocrine therapy and the use of chemotherapy in patients with early-stage HR-positive, HER2-negative breast cancer.Rao: There are several studies that have informed our knowledge to date. Overall, what we're seeing is that 10 years of endocrine therapy may be superior to 5 years. We have a lot of different options of how to give endocrine therapy, whether it should be 10 years of tamoxifen, 5 years of tamoxifen followed by 5 years of an AI, or other combinations of the 2 therapies.

Are compliance rates poor with extended adjuvant endocrine therapy?

Is there any benefit with this therapy beyond 10 years?

Which patients are eligible for de-escalated treatment and how is that determined?

In which patient populations should these genomic assays be used?

Could you discuss the analysis of the association between clinical outcomes and race in patients enrolled in the TAILORx trial?

What else will be the focus of future research in this space?

What is the biggest takeaway for your colleagues?

We know that one of the major AEs of these therapies—specifically AIs—is decreased bone density and increased fracture rate. Therefore, we have to look at what the patient’s bone health is and how that is holding up.Compliance is always an issue with adjuvant endocrine therapy. One of the points from the IDEAL trial was that the patients who were randomized to receive 5 years of additional therapy versus 2.5 years of additional therapy had considerably lower compliance rates. We do have to take that into consideration.I believe that there are ongoing studies looking at this, but we're too early into that to get any conclusive information yet.The nice thing is we now have multiple genomic platforms that we can use to determine which patients with early-stage breast cancer would benefit from adjuvant chemotherapy. If we can pick out those tumors that have a higher risk of recurrence, we can avoid overtreatment of the majority of patients with early-stage breast cancer and focus on appropriately treating the patients at higher risk.Right now, the TAILORx study showed us that the Oncotype DX assay is used in the estrogen- and/or progesterone receptor—positive, HER2-negative, node-negative patient population. The MINDACT trial [used the MammaPrint assay in] patients with lymph node-negative as well as -positive disease.Kathy Albain, MD, of Loyola University Medical Center, looked at the TAILORx results and tried to analyze them based on race. She found that in a controlled trial setting in which patients all received the same treatment and seemed to have similar adherence to treatment; African-American patients seemed to do worse than white patients, even if they were in the same recurrence score group. This tells us that there's something more to the biology of the disease. That should be an area that is focused on in future research.That's a loaded question because there are so many areas that we need to do research in. There is a lot of great ongoing research in these areas, looking at tailoring therapy to the right patient.I hope that we can all learn to look at each patient individually and try to decide, based on their risk of recurrence, [if they need additional therapy] and how they're going to tolerate treatment. Additionally, by gaining information from looking at the biology of their tumor, we can learn how to appropriately treat each patient.