Michelle Tregear, PhD, a 16-year breast cancer survivor, serves as the chief programs officer for the National Breast Cancer Coalition (NBCC). Before joining the NBCC, she was a project director and senior researcher at AFYA Inc. and the ECRI Institute, where she directed dozens of federal contracts largely with the Department of Health and Human Services. Tregear holds a Doctorate of Philosophy in Psychology from the University of Colorado, Boulder. She has held postdoctoral fellowships at the University of Colorado, Boulder, Harvard Medical School, and the University of Pennsylvania. Tregear attended the 2025 ASCO Annual Meeting.
For many women diagnosed with early-stage breast cancer, the words “chemotherapy,” “radiation,” or “surgery” immediately evoke fear – not only because of the diagnosis itself, but also due to the often harsh and sometimes long-lasting side effects of these treatments. But advances in research are beginning to show that some women may not need as much treatment as traditionally given – and in some cases, may not benefit from it at all.
At one of the many educational sessions at the 2025 American Society for Clinical Oncology conference in Chicago, international experts in breast oncology, radiation therapy, and surgery explored emerging research on how to safely de-escalate treatment – reducing or even eliminating certain procedures or medications – while still giving patients the best possible chance for a cure.
Why De-escalate Treatment?
Modern breast cancer treatments have significantly improved survival rates, with annual breast cancer deaths declining by 44% since the peak in 1989.
But the long-term side effects of treatment can profoundly impact quality of life. These may include heart damage, cognitive impairment (“chemo brain”), fatigue, lymphedema (arm swelling), pain and neuropathy, early menopause, and more.
As a result, researchers are asking an essential question: Can we personalize care so that women receive only the treatments they truly need?
Examining Biology to Avoid Chemotherapy
Medical oncologist Nadia Harbeck, MD, PhD, of the University of Munich in Germany opened this session by discussing ongoing research into how we can safely reduce or “de-escalate” the use of chemotherapy for early breast cancer using biomarkers – biological tools that provide insight into a tumor’s behavior.
For instance, in hormone receptor-positive, HER2-negative early breast cancer with zero to three lymph nodes involved, gene expression tests such as Oncotype DX and MammaPrint have become critical in treatment decision-making. Pivotal studies like the TAILORx trial have shown that women with low recurrence scores (as measured by the test) can safely not have chemotherapy.
In the RxPONDER trial, younger, premenopausal women with low genomic risk (based on the recurrence score) still appear to benefit from chemotherapy, possibly because the treatment also suppresses ovarian function, which may play a role in controlling the cancer.
The ongoing OFSET trial compares whether premenopausal women with hormone receptor-positive breast cancer can safely receive endocrine therapy (ET) plus temporary ovarian suppression instead of chemotherapy. If it’s effective, it could offer similar benefits without the long-term side effects associated with chemotherapy.
Another promising strategy currently in clinical trials is called the “endocrine response assessment,” which involves testing how tumors respond to a short course of endocrine therapy before surgery.
Trials such as West German Study Group ADAPT and ADAPTcycle are using this approach to help predict who will benefit from additional treatment like chemotherapy and who might be able to do without. For women whose tumors respond well to hormonal therapy, chemotherapy may be safely omitted.
Some studies are even testing whether targeted drugs, such as CDK4/6 inhibitors, could replace chemotherapy altogether in certain patients. However these strategies are still being tested in clinical trials.
In HER2-positive early breast cancer, where treatment usually includes chemotherapy plus HER2-targeted therapy, researchers are studying whether some patients can safely receive less treatment.
A promising genomic test called HER2DX may help identify people with low-risk tumors who are likely to respond well to less treatment. Early studies suggest HER2DX may be able to help guide decisions such as reducing chemotherapy or using HER2-targeted therapy alone in specific cases. But more prospective clinical trials are needed before HER2DX-guided de-escalation becomes part of routine clinical care.
Rethinking Radiation
Radiation oncologist Icro Meattini, MD, of the University of Florence in Italy said that while radiation has played a key role in reducing recurrence, “Some women may no longer need as much of it, especially those with favorable biology and small tumors.”
For example, women who have a complete response to chemotherapy before surgery (meaning no cancer is found afterward) may be able to skip radiation to the underarm lymph nodes. This method was tested in a recent study called B51, which showed no difference in recurrence rates between women who got node radiation and those who didn’t.
Meattini stressed that radiation decisions should be based on many factors: tumor type, age, surgery type, and response to therapy. He also said radiation can safely be combined with most newer drugs like pembrolizumab (Keytruda) and trastuzumab (Herceptin), but not yet with all types, such as CDK4/6 inhibitors.
Surgery: Less Is More
For decades, removing many lymph nodes from under the arm was standard practice. But it often led to pain, stiffness, and swelling. Today, many women can avoid it entirely.
Breast surgeon Elizabeth Berger, MD, of the Yale School of Medicine, highlighted how studies like Z11, IBCSG 23-01, and AMAROS have shown women with limited lymph node involvement can safely stop at a sentinel lymph node biopsy – a much smaller procedure with far fewer side effects.
And now, for women over age 70 with small, hormone-sensitive tumors and no signs of node involvement on ultrasound, studies like SOUND and INSEMA suggest we can skip node surgery altogether. This spares patients unnecessary complications without compromising their outcomes.
Even in women who get chemotherapy first (known as neoadjuvant therapy), new research supports fewer lymph node procedures if the cancer has responded well.
The Future: Smarter, More Personalized Care
All three speakers emphasized the same theme: we’re moving toward precision oncology, where decisions are driven not just by tumor size or number of nodes, but by biology, response, and risk.
For some, that means no chemo. For others, no radiation. For still others, no surgery in the armpit at all.
But caution is key. These decisions must be based on high-quality evidence from clinical trials and made within health care teams that include oncologists, surgeons, and radiation specialists, and, importantly, the patient.
Show Sources
Photo Credit: E+/Getty Images
SOURCES:
ASCO Educational Book: “Multimodal De-Escalation Strategies in Early Breast Cancer.”
American Cancer Society: “Breast Cancer Facts & Figures.”
