Uncovering inequalities in breast cancer immunotherapy access

Triple-negative breast cancer (TNBC) is an aggressive form of the disease that accounts for 15% of all breast cancer cases. Black women are twice as likely as white women to be diagnosed with TNBC and 28% more likely to die from it.

In a new study published in JAMA Network Open, University of Chicago researchers Jincong (Jason) Freeman, MPH, MS, and Frederick Howard, MD, analyzed data to identify trends that could shed light on why Black women with TNBC have worse survival rates. Since new immunotherapy treatments for metastatic and early-stage TNBC were approved in 2019 and 2021, Howard and Freeman also examined disparities in access to these new treatments.

While they found that much of the inequality they observed between racial and ethnic groups could be explained by socioeconomic disparities, they also found that Black women with TNBC were less likely to receive immunotherapy treatment even when accounting for those factors.

What is triple-negative breast cancer?

“The term ‘triple-negative’ comes from the fact that we use three markers to classify every breast cancer diagnosis: estrogen, progesterone and HER2. Cancers that lack all of these are termed triple-negative,” Howard said. “Each of these markers indicates a sensitivity to specific treatments.”

In addition to being associated with higher rates of proliferation and growth, the lack of these easily targeted receptors is what makes TNBC cells especially difficult to treat. While effective therapies exist to target estrogen, progesterone and HER2 markers on cancer cell surfaces, these are ineffective against TNBC cells. For a long time, chemotherapy was the only option for patients with TNBC.

“In the past, HER2-positive breast cancer was considered to have as negative an outlook as triple-negative breast cancer. But now, with therapies that target the HER2 pathway, it has become one of the most treatable,” Howard said. “Until recently, we lacked similar therapies specifically targeted for TNBC, but immunotherapy is changing that paradigm.”

What are immunotherapies for TNBC?

Immunotherapies are a class of treatments that harness the body’s immune system to fight disease. It is particularly promising for breast cancers, whose cells accumulate genetic mutations as they multiply, creating new, foreign proteins that can be detected easily by the immune system. Since 2019, two immunotherapy drugs have been approved for treating TNBC. Immunotherapy and chemotherapy are intended to be used in combination, attacking the cancer two different ways.

Given that immunotherapies for TNBC are still relatively new, Howard’s and Freeman’s investigation also provided a first look at how these therapies affect treatment response in patients with TNBC. Specifically, they assessed pathologic complete response — a measure of whether no signs of cancer remain — for patients with early-stage TNBC, and survival time for patients with metastatic TNBC.

Analyzing the available data

“Since immunotherapy drugs for TNBC were approved a few years ago, I wanted to use the data across that time to assess how much it is used in practice,” Freeman said. “Are there positive differences in treatment outcomes? Are there racial disparities in immunotherapy response?”

Howard and Freeman analyzed data from the National Cancer Database, which covers 72% of new cancer cases across 1,500 Commission of Cancer-accredited cancer care facilities in the U.S. They studied over 10,000 TNBC patients who received treatment between 2017 and 2021.

In addition to the treatment regimen, Howard and Freeman were interested in each patient’s race, ethnicity, the type of treatment facility and various socioeconomic factors (e.g., health insurance status, median household income, rural-urban areas).

Revealing and exploring TNBC treatment disparities

They found that patients of other ethnic groups (delineated in the study as white, Asian or Pacific Islander, Hispanic and other) all received similar rates of immunotherapy treatment, yet Black patients were less likely to receive immunotherapy.

While most of the difference between racial groups was accounted for by differences in patients’ socioeconomic status, Black patients with metastatic TNBC were still 37% less likely to receive immunotherapy treatment than white patients. This is consistent with previous findings that Black women with TNBC are also more likely to receive lower doses of chemotherapy and are less likely to undergo surgery.

“This disparity could be multifactorial,” Howard said. “The possibilities range from the providers — maybe patients of certain racial groups see providers that aren’t completely up to date on the latest treatments — to the fact that these immunotherapy drugs are only approved for patients with specific marker testing results.”

The current immunotherapy treatments approved for breast cancer require the cancer to be positive for a specific checkpoint inhibitor: a protein that cancer cells use to camouflage themselves from the body’s immune system.

By targeting this protein, immunotherapy treatments make it easier for the immune system to recognize and attack cancer cells. However, there are multiple tests that can determine if patients are suited for immunotherapy treatment by checking if they are positive for a specific checkpoint inhibitor. It’s possible that different tests yield different results, perhaps due to biological differences between racial and ethnic groups, such as variations in programmed cell death protein ligand 1 (PD-L1) expression.

The National Cancer Database, however, lacked specific data about whether patients were tested for sensitivity to immunotherapy treatment, the method of testing and the type of immunotherapy drug that was administered.

Next steps in TNBC treatment research

Howard and Freeman intend to address these limitations of their current study in future studies. “There are some large datasets that we’re looking to query to see if we can find more granular information,” Howard said. “There are many companies that do both genomic testing as well as biomarker testing, who have also done some of the analysis on race and sensitivity to these immunotherapies.”

“We were also only able to assess immediate readouts of treatment response for early-stage TNBC,” Freeman added. “We don’t have access to longer-term data yet, but I would be interested in following up in a few years to see survival outcomes of immunotherapy-treated patients with early-stage TNBC.”

Looking toward a brighter future

Some of the broad trends that Howard and Freeman observed inspire hope for the efficacy of immunotherapy in treating TNBC.

“I wasn’t sure that immunotherapy would be picked up quickly enough to see clear trends in the dataset, because we were only looking at the first few years since these drugs were approved,” Freeman said. “But it’s great that we do see there has been rapid uptake in using this treatment.”

Furthermore, Howard’s and Freeman’s analysis showed no difference in pathologic complete response and overall survival between white and Black patients with immunotherapy. However, many patients that they observed were likely treated as part of clinical trials and therefore experienced highly controlled settings and dosages, which may not be the case for all immunotherapy recipients.

“I think the fact that outcomes are similar with this kind of uniform treatment, at least in this preliminary look, is reassuring,” Howard said. “This could be a good sign that we're starting to bridge some of the gaps in treatment outcomes.”

While these initial results are inspiring, it’s clear that much more work needs to be done to ensure equal access to life-saving treatment. “Patients without insurance and in community cancer centers are less likely to receive immunotherapy and therefore experience the worst treatment outcomes,” Freeman said. “How can we address uninsured patients? We could expand trial networks to ensure that newer treatments reach more patients, especially those in more disadvantaged communities.”

“Our study gave us a preliminary look at some of the systems-level factors, like insurance status and treatment facility, that create disparities in access to these medications,” Howard said. “But more work definitely needs to be done. From this study we can derive a lot of factors that underlie these differences in access, and those will need to be evaluated further.”

“Trends and Disparities in the Use of Immunotherapy for Triple-Negative Breast Cancer in the US” was published in JAMA Network Open in February 2025. Additional authors from the University of Chicago include Dezheng Huo, Sarah Shubeck, Nan Chen, Sudha Yarlagadda, and Rita Nanda.

This study was supported in part by the Agency for Healthcare Research and Quality (R03HS025806), the Breast Cancer Research Foundation (BCRF-23-071), the U.S. Department of Defense (BC211095 and BC211095P1), the National Cancer Institute (P20CA233307 and K08CA283261), the Cancer Research Foundation, the Lynn Sage Breast Cancer Foundation, the National Institute on Aging (T32AG000243), and the Susan G. Komen^® Breast Cancer Foundation (TREND21675016). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute and the National Institute on Aging.