It may come as no surprise that breast cancer is the most common cancer in women worldwide. In the United States, about 275,000 women are diagnosed with breast cancer each year. Triple-negative breast cancer (TNBC) is a particularly aggressive form that has a heightened risk of metastasis within 3 years of cancer diagnosis. TNBC is more common in women under 40 years old and is twice as common in Black women as compared to White, American Indian/Alaska Native, Hispanic, or Asian/Pacific Islander women in the United States. TNBCs lack expression of key hormone receptors (estrogen receptor [ER], progesterone receptor [PR] and epidermal growth factor receptor 2 [HER2]). Because of this, they do not respond to ER and HER2-targeting therapies. The absence of classic breast cancer targets prompted the search for alternative ways to treat TNBC cells.
Starting in 2019 and continuing in subsequent years, new targeted therapies for TNBC became available. These included poly ADP-ribose polymerase inhibitors (PARPi) for patients with germline BRCA1/2 mutations or combined use of various PD-(L)1 or PD-1 inhibitors with chemotherapy. The PARPi blocks cell machinery from repairing DNA following damage—this is particularly lethal to cancer cells with mutations in other genes involved in DNA repair—and PD-(L)1 or PD-1 immune checkpoint inhibitors increase T cell mediated cancer cell killing. It is now about 5 years since the start of these alternative TNBC treatments, but how they impact patient survival remains unexplored. To determine the effect of these new therapies on the 5-year survival rates of metastatic TNBC (mTNBC) patients, Dr. Sara Hurvitz, the Director of the Clinical Research Division at Fred Hutchinson Cancer Center, and her colleagues performed a retrospective analysis using data collected from time periods pre- and post-PARP/PD-(L)1 inhibitor implementation. These data, published in the Oncologist, demonstrated an underwhelming improvement in 5-year survival rates for mTNBC patients following the use of PARP/PD-(L)1/PD-1 inhibitors to treat mTNBC, but these minimal improvements may stem from limited access to the newer therapies.
The retrospective analysis included data from patients in the United States diagnosed with mTNBC between 2011-2017 (early cohort) or 2018-2022 (late cohort). The early cohort represented patients who primarily received chemotherapy for their first line treatment (~96% of patients). The late cohort still included a large proportion of patients receiving chemotherapy (~65% of patients), but about a third received newer first line therapies (~2% of patients received PARPi for BRACA1/2 mutations and ~33% of patients were treated with PD-(L)1 inhibitors). With these two cohorts, the researchers investigated the change in patient 5-year survival rates following the implementation of PARP and PD-(L)1 inhibitors. The median 5-year survival rate improved slightly from 10.9 months in the early cohort to 11.9 months in the later cohort of mTNBC patients.
For all patients included in this study, about half survived 12 months and a third survived two years following mTNBC diagnosis. Due to the aggressive nature of this cancer, “one-third of patients who received first-line treatment did not survive to second-line care,” stated Dr. Hurvitz. These findings emphasize the importance of effective first line therapies for mTNBC. However, another barrier could be implementation of these newer therapeutic approaches. In the late cohort used in this study, only ~35% of patients received either PARPi for BRACA1/2 mutations or PD-(L)1 inhibitors as their first line therapy. Therefore, increasing the number of patients prescribed either PARPi for BRACA1/2 mutations or broadly relevant PD-(L)1 inhibitor may improve the 5-year survival rates of mTNBC patients. Furthermore, the addition of other targeted therapies that improve mTNBC survival rates like the PD-1 inhibitor (KEYTRUDA) may continue to raise awareness and implementation rates of alternative therapies as opposed to sole use of chemotherapy as the first line treatment for mTNBC. “This real-world study highlights the poor outcomes in triple negative metastatic breast cancer, showing limited survival gains despite new therapies,” shared Dr. Hurvitz. “The modest survival benefit—around one month—points to an urgent need for better initial treatments and improved access to existing therapies.” It will be critical to follow survival trends for mTNBC patients over the coming years to better understand the impact of new therapies on patient survival rates.
The spotlighted research was funded by Gilead Sciences, Inc.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Sara Hurvitz contributed to this work.
Punie K, Kurian AW, Ntalla I, Sjekloca N, Estrin A, Dabrowski EC, Lai C, Hurvitz S. 2025. Unmet need for previously untreated metastatic triple-negative breast cancer: a real-world study of patients diagnosed from 2011 to 2022 in the United States. Oncologist. 30(3):oyaf034.
Science spotlight writer Annabel Olson is a postdoctoral research fellow in the Nabet lab at Fred Hutchinson Cancer Center. Her research focuses on studying the mechanisms that drive cancer development for both genetic and virus-associated cancers. A key tool in her research is the use of targeted protein degradation to dissect dysregulated signaling pathways in cancer and to double as a relevant pre-clinical therapeutic platform.
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