Dr Wander on Managing HR+ Advanced Breast Cancer in the Clinic

Seth Wander, MD, PhD, instructor, medicine, Harvard Medical School; medical oncologist, Massachusetts General Hospital, discusses how he approaches therapeutic treatment for patients with hormone receptor (HR)–positive advanced breast cancer in the clinic, as well as how ongoing clinical trials and available data affect this decision.

In clinical practice, without definitive data to guide treatment decision-making for different subgroups of patients with HR-positive metastatic breast cancer, Wander says he takes a tailored treatment approach based on patients’disease progression and prior treatment history. For many patients who are newly diagnosed with untreated HR-positive metastatic breast cancer or who have experienced a recurrence after a prolonged period off anti-estrogen therapy, he typically uses a frontline regimen that combines an aromatase inhibitor with a CDK4/6 inhibitor. Ribociclib (Kisqali) is often the CDK4/6 inhibitor of choice in this patient population, due to its proven efficacy and tolerability, Wander explains.

For patients with more aggressive disease, particularly those whose cancer has progressed on or shortly after adjuvant anti-estrogen therapy, the focus shifts to clinical trial opportunities, he continues. These patients likely have a poorer prognosis with standard frontline therapy, and novel approaches are essential, according to Wander. In this context, trials with innovative anti-estrogen agents, targeted therapies, and combination regimens are critical, Wander reports. Until new data become available, the standard of care (SOC) for this subgroup remains fulvestrant (Faslodex) combined with a CDK4/6 inhibitor, he says, noting that the choice between the available CDK4/6 inhibitors can be individualized based on data in the second-line metastatic setting.

However, there is a clear need for improved outcomes for these patients, Wander expands. Genomic sequencing is becoming increasingly important in guiding treatment strategies, he emphasizes. For instance, patients with PI3K pathway alterations may benefit from alpelisib (Vijoice) or capivasertib (Truqap), whereas those with ESR1 mutations could be candidates for next-generation anti-estrogen therapies, he says. Additionally, some patients may have alterations in other key pathways, such as RAS, Wander explains. For these patients, there may not yet be SOCtreatments, but clinical trials offer promising opportunities, he notes. As research progresses, targeting these pathways will likely become a more integral part of treating patients with metastatic breast cancer, expanding the therapeutic options for these patients, Wander concludes.