Breast cancer treatment has changed dramatically over the past decade. One of the most important advances has been our growing ability to understand the biology of each patient’s cancer and use those insights to guide treatment decisions more precisely. That shift is helping make personalized cancer care a reality.
Antibody-drug conjugates, immunotherapy, targeted therapies, and new endocrine treatments have improved outcomes across breast cancer subtypes and expanded our therapeutic options.
The next major advances will come from our ability to understand which therapies are most appropriate for an individual patient based on the biology of their cancer and on expanding these classes of agents with better or alternative tumor targeting.
Today, we can characterize tumors at a molecular level, identify biomarkers that predict response and resistance, and tailor therapy with far greater precision. However, these strategies are still not feasible or are not effective in all cancers.
Precision in HER2-positive, triple-negative, and hormone receptor-positive disease
Breast cancer comprises multiple biologically distinct diseases that require different treatment approaches.
In HER2-positive breast cancer, a new antibody-drug conjugate has transformed treatment and improved outcomes in both metastatic and early-stage settings. We have also seen significant effectiveness with oral enzyme inhibitors. Both of these new therapeutic approaches offer more effective treatment for brain metastases, a major challenge in the treatment of HER2-positive disease. Additional HER2-targeted ADCs and antibodies are now being studied and have the potential to further improve patient outcomes.
In triple-negative breast cancer, we have moved TROP-2 targeted antibody-drug conjugates into first-line metastatic treatment just this year, and we continue to explore how best to integrate immunotherapy and novel agents. We are particularly interested in improving treatment options for patients with residual disease after neoadjuvant treatment because these patients remain at substantial risk for recurrence. Clinical trials are evaluating TROP-2 antibody-drug conjugates and novel antibodies in the post-neoadjuvant setting to determine whether they can improve outcomes for patients with early-stage triple-negative breast cancer.
For hormone receptor-positive disease, the recent development of oral selective estrogen receptor degraders and newer targeted therapies have created important new options for overcoming resistance mechanisms that previously limited treatment effectiveness. We continue to evaluate how these therapies should be incorporated throughout the treatment continuum—with the goal of combination therapy rather than relying on single endocrine therapies alone.
Across all breast cancer subtypes, deeper insights into tumor biology are helping us to better match therapy to individual patients.
The promise of molecular monitoring
Circulating tumor DNA is emerging as one of the most promising tools in breast cancer research.
For years, oncologists have relied on imaging, clinical symptoms and traditional tumor markers to assess treatment response and disease progression.
The ability to monitor cancer through ctDNA creates opportunities to detect changes earlier and potentially intervene before progression becomes clinically apparent. Changing therapy based on emerging resistance markers is an intriguing strategy that has been evaluated with improvement in disease control for patients with advanced hormone receptor-positive disease, but controversies remain including understanding best sequencing of therapy.
Across all breast cancer subtypes, deeper insights into tumor biology are helping us to better match therapy to individual patients.
Several important questions have arisen. Should rising quantitative ctDNA in patients with advanced disease prompt treatment changes before disease progression appears on imaging, and could this be a trigger for imaging? Will changing treatment based on emergence of ctDNA in the early-stage setting (which clearly identifies patients at high risk of recurrence) reduce the incidence or delay appearance of metastatic disease?
These are questions we are actively studying at City of Hope, along with our national and international colleagues.
I currently lead the U.S. portion of the international TAILORswitch study, which will evaluate whether treatment should be changed when ctDNA rises despite the absence of conventional evidence of progression. The trial is also examining whether molecular monitoring can be incorporated into the way we follow patients over time. The trial is a collaboration between Unicancer in France and the Alliance Foundation in the U.S.
In short, we are evaluating whether biologic signals can help us intervene earlier, optimize treatment selection and improve outcomes.
A more sophisticated approach to treatment de-escalation
One area generating increasing interest is individualizing therapy based on response to therapy in early-stage disease. This includes both escalating treatment for delayed or poor response, and de-escalating therapy for excellent early response.
De-escalation depends on identifying patients whose cancers are likely to respond faster and better to treatment and may require less intensive therapy while still maintaining excellent outcomes. Biomarkers and response assessment are central to making those decisions safely.
City of Hope has been an active participant and major enrolling center within the I-SPY clinical trial network, which continues to explore novel therapies to improve outcomes along with the application of biomarkers, imaging and other tools to refine treatment decisions in the neoadjuvant setting. Researchers are evaluating the use of ctDNA clearance along with imaging and pathology to help determine when patients can proceed safely to surgery and whether treatment can be further personalized.
This work helps us better align treatment intensity with tumor biology, reducing treatment burden for some patients while identifying others who may benefit from more effective therapies.
We are also participating in efforts focused on older adults with breast cancer, where balancing treatment effectiveness and treatment tolerance is particularly important.
Leadership across the breast cancer research continuum
City of Hope is contributing to breast cancer research across the continuum, from therapeutic development and biomarker discovery to supportive care and survivorship.
Our investigators are evaluating next-generation antibody-drug conjugates, new antibodies, emerging endocrine therapies and targeted therapy combinations. We continue to expand research focused on brain metastases and are exploring bispecific antibody approaches in both metastatic and early-stage disease.
By integrating translational science, biomarker development and clinical trials, we are working to move promising discoveries into patient care more quickly.
By integrating translational science, biomarker development and clinical trials, we are working to move promising discoveries into patient care more quickly.
Improving outcomes also requires addressing the long-term effects of treatment.
A major focus of our work involves reducing treatment-related toxicity and improving quality of life. We are studying strategies to prevent peripheral neuropathy, address endocrine therapy-related symptoms, and evaluate supportive interventions such as acupuncture and Tai Chi.
As outcomes improve, preventing and managing long-term treatment effects becomes increasingly important.
Looking ahead
I am encouraged by our growing ability to understand the biology of each patient’s cancer and to use that information to guide treatment decisions.
That understanding is helping us develop more precise therapies, identify resistance earlier, optimize treatment intensity and reduce treatment-related toxicity.
Biology-guided treatment strategies, molecular monitoring and increasingly personalized therapy will help drive the next generation of advances in breast cancer care.
City of Hope® is one of the largest and most advanced cancer research and treatment organizations in the U.S. To learn more about City of Hope, visit: www.cityofhope.org.
Discover the latest innovations in cancer research on City of Hope’s new podcast, “On the Edge of Breakthrough: Voices of Cancer Research.” Available on Spotify, Apple Podcasts and at cityofhope.org/edge-of-breakthrough .
