Experts Explore How to Treat Each Stage of Triple-negative Breast Cancer

February 12, 2026 by

At the San Antonio Breast Cancer Symposium (SABCS) 2025, which is co-organized by the American Association for Cancer Research (AACR), experts shed light on the rapidly evolving landscape for triple-negative breast cancer (TNBC) treatment—reviewing current options for each stage of the disease and highlighting the potential advances to come. 

Treating Stage 1 TNBC: The Role of Chemotherapy

Patients with TNBC are ineligible for hormone therapies and human epidermal growth factor receptor 2 (HER2)-targeted therapies, so chemotherapy before surgery (neoadjuvant) and after surgery (adjuvant) has long been a mainstay of treatment for these individuals. But given the toxic nature of the treatment and the typically better prognosis of patients with stage 1 TNBC, many are wondering whether patients with these earliest-stage cases can skip neoadjuvant chemotherapy.

Who Benefits From Neoadjuvant Chemotherapy?

Addressing the question of whether neoadjuvant chemotherapy still has a place for stage 1 TNBC, Elie Rassy, MD, MPH, a medical oncologist at Institut Gustave Roussy in France, pointed to several clinical trials in which the treatment significantly improved outcomes for patients with stage 1 tumors measuring more than 5 mm. 

Current guidelines recommend neoadjuvant chemotherapy for patients with large stage 1 TNBC tumors, whereas patients with low-risk TNBC tumors may be able to safely skip neoadjuvant chemotherapy.

Based on these results, he argued that, for patients with larger stage 1 tumors, neoadjuvant chemotherapy still plays an important role—a conclusion that aligns with recommendations from the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and the St. Gallen International Breast Cancer Consensus. 

While all of these major medical groups recommend neoadjuvant chemotherapy for certain stage 1 TNBCs, the tumor size for which they recommend it varies: NCCN recommends chemotherapy for tumors larger than 5 mm, ASCO and ESMO recommend it for tumors larger than 10 mm, and St. Gallen recommends it for tumors 15 mm or larger.

As far as which chemotherapy agents to use in this setting, data support the benefit of anthracyclines for these larger tumors, while there is no evidence to support the use of platinum-containing agents, said Rassy.

He noted that there is also no evidence to support the use of adjuvant anthracyclines or platinum for patients who do not experience pathologic complete response after neoadjuvant chemotherapy. Instead, these patients may benefit from adjuvant treatment with a PARP inhibitor (if they have germline BRCA mutations) or with capecitabine. 

Who May Be Eligible to Skip Neoadjuvant Chemotherapy?

Patients whose stage 1 TNBCs are considered low-risk based on their small size or favorable histology may be able to safely skip neoadjuvant chemotherapy, as several retrospective studies have found positive outcomes for these patients even in the absence of neoadjuvant chemotherapy. 

Guidelines from the NCCN and ESMO, therefore, state that neoadjuvant chemotherapy may be omitted for patients with lymph node-negative tumors smaller than 5 mm (T1aN0 tumors). ESMO also recommends omitting neoadjuvant chemotherapy for tumors that are of the adenoid cystic, secretory, or medullary histologic subtypes.

At this time, there is not enough information to determine whether neoadjuvant immunotherapy would benefit patients with stage 1 TNBC. Rassy explained that patients with stage 1 TNBC have not been included in most clinical trials for immunotherapy, or have been included at too low of numbers to glean efficacy.   

Treating Stage 2-3 TNBC: A Shifting Standard of Care

Like stage 1 TNBC, stage 2 and 3 cases have historically been treated with chemotherapy. In recent years, however, treatment for stage 2-3 TNBC has undergone a major change with many patients now receiving immunotherapy as part of neoadjuvant and adjuvant therapy. Gustavo Werutsky, MD, PhD, a medical oncologist at Hospital Moinhos de Vento in Brazil, discussed the implications of the new treatment approach.

What Are the Benefits of Immunotherapy for Stage 2-3 TNBC?

The new standard of care came in response to groundbreaking results from the KEYNOTE-522 trial, in which patients treated with the immunotherapy pembrolizumab (Keytruda) and chemotherapy before surgery, and pembrolizumab alone after surgery, had significantly greater responses than those treated with chemotherapy alone. This led the U.S. Food and Drug Administration (FDA) to approve the regimen for certain cases of early-stage TNBC in 2021. 

Analyses conducted in real-world patients (i.e., those not enrolled in the clinical trial) have not only confirmed the efficacy of the new regimen (albeit with lower response rates than seen in the trial) but have also shown that it is cost-effective, said Werutsky. 

What Are the Downsides of Immunotherapy for Stage 2-3 TNBC?

Immunotherapy improves outcomes for some patients with stage 2-3 TNBC but comes with added toxicity. Researchers are exploring ways to maximize benefits while reducing risks associated with the treatment.

While acknowledging the benefits of this new treatment option, patient advocate Janice Cowden explained that advances like immunotherapy have resulted in “progress for some but toxicity for many,” alluding to the higher toxicity and greater risk for chronic conditions associated with immunotherapy. Extending survival is an important goal—but not the only one, she said, emphasizing that quality of life matters, too. Moreover, Werutsky noted that immunotherapy-associated conditions can be particularly problematic for TNBC patients, who tend to be younger and would, therefore, have to manage chronic conditions for a long time. 

Researchers are working to combat these concerns in many ways, including finding ways to tailor immunotherapy to certain patients, testing lower doses, and combining immunotherapy with different therapeutics. 

Can Neoadjuvant and Adjuvant Immunotherapy Be Tailored to Each Patient?

Identifying which patients are most likely to benefit from the treatment would allow patients whose tumors are unlikely to respond to instead receive the former standard of care (neoadjuvant chemotherapy) and avoid the additional toxic side effects associated with immunotherapy.

One potential is to use the number of immune cells present in the tumor to predict responses to immunotherapy, as tumors with greater infiltration of immune cells have been shown to be more responsive. Using pretreatment levels of circulating tumor DNA (DNA shed from the tumor into the bloodstream) to predict outcomes is another idea that has shown promise.

Moreover, monitoring how levels of circulating tumor DNA change during immunotherapy could allow physicians to adjust treatment based on how well the tumor is responding, since decreasing circulating tumor DNA is typically associated with reduced disease burden. 

What Are Potential Strategies for Reducing Toxicity?

Researchers are studying whether lower doses of immunotherapy would reduce toxicity while maintaining the treatment’s efficacy, with results from clinical trials supporting this idea. 

Others are exploring combining neoadjuvant immunotherapy with antibody-drug conjugates instead of with chemotherapy, or using an antibody-drug conjugate as a potentially less toxic alternative to immunotherapy in the adjuvant setting. 

Treating Stage 4 TNBC: An Evolving Landscape

While survival rates for other metastatic breast cancer subtypes have dramatically increased since 2000, the improvement for TNBC has only been modest. But Sara M. Tolaney, MD, MPH, a medical oncologist at Dana-Farber Cancer Institute, said that there is reason for optimism due to the recent approvals of pembrolizumab, sacituzumab govitecan (Trodelvy), and trastuzumab deruxtecan (T-DXd; Enhertu) for certain patients with metastatic TNBC—as well as clinical trial results that suggest these and other therapeutics may be effective in the first-line setting as well. 

What Are Emerging First-line Treatment Strategies for Metastatic TNBC? 

With roughly half of patients with metastatic TNBC unable to receive subsequent lines of therapy due to health deterioration or other reasons, Tolaney emphasized the importance of ensuring that patients receive the most effective therapies in the first-line setting. She shared how new data hold the potential to transform the first-line treatment of metastatic TNBC.

As one example, she pointed to emerging data supporting the first-line use of the TROP2-directed antibody-drug conjugates sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd; Datroway) in this patient population. These targeted therapeutics use antibodies to selectively deliver toxic agents to TROP2-expressing cells.

Tolaney anticipates a new first-line treatment landscape based on whether patients’ tumors express PD-L1, with those with PD-L1-positive cancers receiving sacituzumab govitecan plus pembrolizumab instead of the current standard of chemotherapy with pembrolizumab. 

For those with PD-L1-negative cancers, she noted that Dato-DXd, sacituzumab govitecan, and PARP inhibition (for patients with germline BRCA mutations) have each shown promise. If both Dato-DXd and sacituzumab govitecan were to be approved for this population, the choice between the two may depend on the patient’s comorbidities and ability to travel for treatment, given the differing dosage schedules.

Janice Cowden; Gustavo Werutsky, MD, PhD; Sara M. Tolaney, MD, MPH; session moderator Marleen Kok, MD, PhD; and Elie Rassy, MD, MPH, at the SABCS 2025 session, “How to Treat TNBC—Triple-Negative Not so Negative Anymore.”

How Is Residual or Recurrent Metastatic TNBC Treated?

Patients who require subsequent lines of therapy may be treated with sacituzumab govitecan, T-DXd (if their tumors are considered HER2-low), PARP inhibition (if they have germline BRCA mutations), or chemotherapy. In the third-line or later line of treatment, pembrolizumab or certain targeted therapies may be indicated for patients whose tumors have particular biomarkers, such as high tumor mutation burden (TMB), high microsatellite instability (MSI-H), NTRK fusions, or RET fusions.

What Treatment Advances Are on the Horizon for Metastatic TNBC?

With the emergence of effective antibody-drug conjugates for metastatic TNBC, researchers continue to explore new designs and their utility in distinct patient populations, Tolaney noted. One area of interest is to test whether antibody-drug conjugates could allow immunotherapy to be effective against PD-L1-negative tumors, and another is to understand how T-DXd, a HER2-directed antibody-drug conjugate, performs against TNBC.

Researchers are also developing therapeutics that simultaneously inhibit PD-L1 and the vascular endothelial growth factor (VEGF) in TNBC, which is a strategy that has shown promise in other cancer types.

While there is still much work to do to improve the lives of patients with TNBC, recent advances and ongoing research highlighted during the session offer hope for the many individuals facing this aggressive disease.