The trend toward de-escalation in breast cancer treatment may be going too far when it comes to patients with inflammatory disease, according to a US cohort study.

While scaling back therapy has been successful for many patients with breast cancer, it hasn’t proven safe for those with inflammatory breast cancer (IBC), an aggressive subtype accounting for about 5% of cases. Guidelines still call for trimodal therapy — a combination of neoadjuvant chemotherapy-based systemic therapy, modified radical mastectomy with axillary lymph node dissection, and postmastectomy radiation.

Multiple studies have linked trimodal therapy to improved survival among patients with IBC. Yet the approach is on the decline in the US, according to new findings published in JAMA Network Open.

Looking at registry data on over 47,000 patients with stage III breast cancer, researchers found that among those with inflammatory disease, trimodal therapy use fell from 34% in 2010 to 24% in 2020 — a relative annual decrease of nearly 5%.

At the same time, patients who received trimodal therapy had better outcomes, including an 8-year overall survival of about 55% vs 40% without it.

The reasons for the pullback from trimodal therapy are unclear, but the study authors suspect patients with inflammatory disease are being swept up in the broader de-escalation trend.

Clinicians may be extrapolating data from other populations with breast cancer despite a lack of supportive data, according to investigators led by José Leone, MD, medical breast oncologist at the Dana-Farber Cancer Institute in Boston.

Two breast cancer surgeons offered additional insights in an accompanying editorial.

Despite the need for “aggressive multimodal therapy” in this patient group, there is building evidence of locoregional treatment de-escalation, wrote Audree Tadros, MD, and Risa Kiernan, DO, of Memorial Sloan Kettering Cancer Center in New York City.

Sentinel lymph node biopsy is increasingly being used in place of axillary dissection. In one recent study, only half of patients with nonmetastatic IBC had a modified radical mastectomy with axillary dissection and no immediate reconstruction, in keeping with guidelines.

According to Tadros and Kiernan, advances in systemic therapy may be fueling the “false perception” that dialing back locoregional management is safe in IBC.

Kathy Miller, MD, medical breast oncologist at Indiana University Health in Indianapolis, said she has also seen reluctance among surgeons to diagnose IBC. They may note findings such as peau d’orange in the record but stop short of using the diagnosis.

When she asks why, Miller said, surgeons cite concerns about the need for axillary dissection and the implications for immediate reconstruction.

Wendy Woodward, MD, PhD, breast radiation oncologist who specializes in IBC, pointed to another issue: a general lack of familiarity with the disease.

“Most people have very little experience diagnosing or treating IBC and fall into more familiar norms that are trending toward de-escalation,” said Woodward, executive director of the IBC clinic at MD Anderson Cancer Center in Houston.

“This is an ongoing problem and crisis in my opinion,” she said.

Sometimes, the diagnosis is missed altogether, so trimodal therapy isn’t offered — while in disjointed care settings, it may not carry through to all members of the treatment team. Woodward has also seen inflammatory symptoms attributed to congestion or otherwise explained away.

To help, she and her colleagues, along with the advocacy group IBC Network Foundation, have launched a nationwide outreach effort through the IBC Connected Community.

They’ve also developed an online diagnostic tool to calculate the probability of IBC on the basis of clinical presentation, as well as an IBC best practices checklist to guide discussions between patients and oncologists.

The efforts fit with the JAMA investigators’ call for “multipronged efforts” to increase guideline-concordant care and research focused specifically on IBC, which is underrepresented in trials.

Data for the study came from the Surveillance, Epidemiology, and End Results cancer registry. Overall, 3227 patients, or 6.8% of the study population, were diagnosed with IBC.

Just over 31% of those patients received trimodal therapy, whereas roughly 73% had neoadjuvant systemic therapy, 73.5% underwent mastectomy, 55% had more than five axillary nodes dissected, and 58% received radiation.

In keeping with historically worse outcomes, breast cancer-specific survival was poorer in IBC, and — in contrast to noninflammatory disease — outcomes did not improve over the study period.

Among the study limitations, the authors noted that some patients may have been ineligible for trimodal therapy due to comorbidities not captured in the registry, whereas others may have progressed on neoadjuvant chemotherapy and become ineligible for surgery.

Still, they concluded, the overall decline in trimodal therapy is concerning.

There was one finding that Miller called “slightly reassuring.” Despite the decline in trimodal therapy, survival trends among patients with IBC remained flat — suggesting that some may be able to skip aspects of the treatment approach without harm.

However, Miller cautioned, survival is a lagging indicator, and changes can take time to emerge.

The study received support from Dana-Farber. Miller is a regular contributor to Medscape. Miller and Woodward reported having no relevant disclosures.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Otto is also an MIT Knight Science Journalism fellow. Email: aotto@medscape.net