Breast cancer is personal: Your treatment should be, too | SABCS 2025

One piece of information that providers use to guide personalized treatment is biomarkers. Biomarkers tell us about the biology of a cancer—— what is going on within cancer cells that might be driving cancer growth. Tests of tumor tissue or blood look for genetic changes, hormones, and proteins that may play a role in cancer growth. Newer, more refined tests give clues about prognosis, how well a treatment is working, or look for early signs that cancer may be coming back.

Imaging (i.e., PET scan or MRI) can be used to measure biomarkers that may play a role in tracking response to treatment. Pathological complete response (pCR) and residual cancer burden (RCB) are ways to measure how much cancer is left by looking at tumor tissue on these scans. Circulating tumor DNA (ctDNA), or liquid biopsy, is a newer tool to measure minimal residual disease burden (MRD), the small amount of cancer cells left circulating in the blood during or after treatment. MRD can only be detected by highly sensitive blood tests. A “clear,” or undetectable, ctDNA level is often a sign of a favorable prognosis. Changing treatments based on ctDNA results is only supported for people with metastatic breast cancer at this time. Multiple presentations at SABCS focused on the potential of ctDNA in the clinic for people with early-stage breast cancer based on a number of clinical trials. The newest approaches being studied combine imaging and ctDNA to guide treatment in the clinic and to track outcomes in clinical trials of new drugs.

Tailoring treatment in early-stage breast cancer

Personalizing therapy in early-stage breast cancer can happen before or after surgery. The goal is to avoid overtreatment by finding the right medicine and doses needed to control the cancer and stop it from coming back. Neoadjuvant therapy — or drug treatment before breast surgery — is often used for larger tumors or cancers that have spread to the lymph nodes.

pCR and RCB are useful predictors of response to neoadjuvant treatment. They are not as helpful at determining improvement after a change in therapy. ctDNA testing takes this a step further. Several studies presented at SABCS reported that ctDNA may offer insight into prognosis in the neoadjuvant setting in all breast cancer subtypes.

PET scans and MRIs are also used as a biomarker before surgery. Some people may be able to skip later rounds of drug therapy and go to surgery sooner based on scan results. Reports from SABCS showed that imaging data, along with scans and biopsies, used in the I-SPY clinical trial found people who would not get more benefit from adding anthracycline-based chemotherapy before surgery.

For adjuvant treatments, multiple clinical trials in all tumor types focus on the use of ctDNA to track MRD. People with high-risk, early-stage hormone receptor-positive breast cancer have many treatment options. Ongoing research explores how to use ctDNA to help determine whether to give a particular person more aggressive treatment or to dial down and avoid over-treating their cancer.

Tailoring treatment in early-stage triple-negative breast cancer (TNBC) is a major area of research focus as well. TNBC can be fast-growing, especially after it spreads. Doctors are balancing the need to treat this type of cancer aggressively against how treatment affects quality-of-life for their patients. Pathological complete response (pCR) is linked to better long-term outcomes. Research in stage II and III TNBC use ctDNA for guided adjuvant therapy based on strong evidence of the association between ctDNA and distant recurrence. Several studies reported early findings that linked certain immune system markers to better or worse outcomes with either immunotherapy or combinations of chemotherapy and other drugs.

Tailoring treatment in metastatic breast cancer

Biomarker testing plays an important and growing role in choosing treatments for metastatic breast cancer (MBC). Circulating tumor cells (CTC) and ctDNA can help predict how well someone will do on a treatment before their cancer progresses. CTC in particular is a very strong indicator of prognosis.

ctDNA testing is used to find certain mutations, or changes in the cancer cell’s genome, such as PIK3 and AKT. This information helps match people with drugs that target those changes. A session at SABCS dedicated to liquid biomarkers like these presented links between ctDNA information and responses to new drug combinations, longer progression free survival, and better quality of life.

Even though biomarker testing is critical to guiding treatment in MBC, not everyone receives it or even knows about it. In some cases, it may not be available because of location or cost.

“Precision medicine should narrow disparities, not widen them,” advocate Tracy Solak says.

To raise awareness of biomarker testing, LBBC became the lead breast cancer organization to adapt No One Missed, a national biomarker testing campaign, to the breast cancer community. Available in English and Spanish, the educational materials answer common questions about biomarker testing in lay language.

In a poster presented at SABCS, LBBC Director of Outreach Theresa Petee shared results of a survey to assess the impact of the materials, which found that:

• While most participants had heard of biomarker testing at the start of the study, only 45% had undergone biomarker testing.
• After reviewing the materials, 61% of participants agreed that biomarker testing is important (compared to 46% beforehand) and 54% agreed that biomarker testing would improve their cancer experience (compared to 36% beforehand).

“We often think that we need to do big splashy programs to influence behavior,” says Petee. “But this effort shows that adapting materials in a sensitive and culturally appropriate way can reach people just as well.”

The biology of a tumor can change, and biomarker tests may need to be repeated.

“Once is not always enough,” says Petee. “Many people do not realize that they might need biomarker testing multiple times during their cancer journey.”

Future directions

Interest in tailoring treatment in breast cancer continues to grow. With so many trials ongoing, doctors are hopeful that a new standard of care will emerge to best understand how to use these results.

In an SABCS session on liquid biopsy, Michail Ignatiadis, MD, PhD, of Institute Jules Bordet noted that “ctDNA is already transforming patient care in early breast cancer, but we need more data from prospective clinical trials with appropriate control arms to understand how best to use it.”

Angela DeMichele, MD, of the University of Pennsylvania and a member of LBBC’s Medical Advisory Board, echoed this message. She called on the advocacy community to help spread the word about the need for resources.

Without more knowledge, doctors and people with breast cancer may be left with difficult decisions about whether and when to use ctDNA testing. Information that does not lead to clear actionable steps may add more stress than value. Also, ctDNA testing technology is still not available to all people with breast cancer, whether due to cost or location. Honest and open conversations between patients and providers — about both the risks and benefits of testing — are critical.