FLEX Study Data Highlight Role of Genomic Testing in Guiding Early-Stage Breast Cancer Treatment

At the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, William Audeh, MD, presented data from the FLEX study, a large real-world database designed to support precision therapy selection in early-stage breast cancer. The FLEX database includes structured clinical data from nearly 22,000 patients across multiple subtypes, stages, and ethnicities, along with extensive genomic profiling of tumor samples. In addition to standard-of-care MammaPrint and BluePrint testing, the study incorporates whole transcriptome analysis, allowing researchers to correlate gene expression patterns with long-term clinical outcomes, including five-year follow-up data for several thousand patients.

Pharmacy Times: The FLEX study provides a depth of real-world genomic data rarely seen in oncology. How might this expanding dataset help pharmacists anticipate toxicity risks, optimize supportive-care strategies, or better counsel patients about expected treatment intensity?

William Audeh, MD: So the FLEX study is a multilevel database that really possesses all of the essential components of what is considered to be an ideal real-world database. There are many real-world databases, but they vary in terms of how useful the information is and how easy it is to extract useful information.

We’ve enrolled nearly 22,000, primarily women with early-stage breast cancer of multiple subtypes, multiple ethnicities, and multiple stages. The way we collect the data is in terms of the clinical information. It’s structured clinical information, so it’s easy to ask questions of it.

What is unique about FLEX is that we also obtain extensive genomic data on the tumor samples coming from the people enrolled in this trial. Of course, we perform MammaPrint and BluePrint as standard-of-care testing, but the study component is whole transcriptome data, where we look at every gene that’s on or off in terms of gene expression and correlate that with outcomes. Because we’ve been running the trial since 2017, we now have several thousand patients who have reached five years of follow-up. That kind of outcomes data is really unique in this environment.

Because it’s real-world data, it reflects what’s happening every day in the clinic. We’ve focused on supporting therapy selection, as we have with the anthracycline data, but new therapies are entering the clinic. CDK4/6 inhibitors and immunotherapy will soon, I think, be approved in hormone-positive breast cancer. We look to the FLEX database to clarify which patients will really need these therapies and how we can identify resistance to these therapies that would direct a physician to avoid using such a drug. With the complexity of these drugs and their interactions, that’s where the oncology pharmacist, I think, is critical for informing clinicians when there’s a choice and which choice may be the best.

Pharmacy Times: As genomic testing becomes more integrated into early breast cancer management, what do you see as the key educational or workflow gaps pharmacists can help address to ensure results are used consistently and effectively across multidisciplinary teams?

Audeh: Unfortunately, not all women diagnosed with breast cancer are treated in a system where there’s a multidisciplinary team that comes together to make therapy decisions. Of course, we all agree that the ideal approach is a team-based circle of care that involves oncology pharmacists, nurses, clinicians, medical oncology, radiation, and surgery. All really need to be communicating about every newly diagnosed patient.

One of the unmet needs you’re asking me about is the use of genomic testing. We can tell that there are many women who are appropriate for genomic testing who are not getting it, where therapy decisions are being made without the benefit of genomic testing. One clear area where oncology pharmacists can help is encouraging the application of genomic testing for early-stage breast cancer as a standard piece of information necessary to make the best choices.

If genomic testing is available and results are available, oncology pharmacists can also help interpret the results. Unlike many other genomic tests, we are focused on supporting therapy selection, not just whether chemotherapy is necessary. That’s a question many assays can answer, including MammaPrint and BluePrint. But should chemotherapy be given prior to surgery, we can predict whether that would be a better approach. If chemotherapy is necessary, we can also help select which drugs may be best. These are all areas where the oncology pharmacist is critical.

Pharmacy Times: Anthracyclines remain potent but carry cardiotoxicity and long-term safety considerations. Based on FLEX and the SABCS data, how might pharmacists collaborate with oncologists to identify patients who may safely omit anthracyclines—and to monitor those who still require them?

Audeh: The concerns about anthracycline involve not only early toxicities but also the risk of late toxicities. The decision to use them needs to be made very carefully, and that hasn’t always been the case prior to having genomic information like the type we presented here at San Antonio this year. It begins with the oncology pharmacist asking whether the patient has had a genomic test that can help guide anthracycline use. At this point, it’s primarily the MammaPrint assay that is most precise in answering that question.

If it’s clear that a patient does not require anthracycline, that’s greatly beneficial. Many instances in which clinicians choose anthracycline without genomic information are in younger women, where there’s a desire to treat aggressively to prevent recurrence. Those women stand to suffer most from unnecessary anthracycline therapy. Beyond cardiotoxicity, there are long-term bone marrow effects that can predispose patients to other problems later in life.

For younger women diagnosed with breast cancer, where there’s often an automatic desire for more aggressive therapy, they are the ones who benefit most from the genomic information that MammaPrint provides, which we presented here at San Antonio.