<p>At the <strong>2025 San Antonio Breast Cancer Symposium (SABCS 2025)</strong>, momentum in HR+/HER2- early-stage breast cancer grew, with signals of progress in adjuvant endocrine therapy with an oral SERD, risk assessment with circulating tumor DNA (ctDNA), and supportive care with a digital tool. The takeaways point toward more proactive, data-guided, patient-centered management for clinicians and their patients.</p> <p><br></p> <p><em>Following these presentations, featured expert Erica L. Mayer, MD, MPH, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Mayer on these findings are presented here.</em></p>

The biggest theme at SABCS 2025 was the movement of therapies and strategies (eg, SERDs and ctDNA monitoring) that are routinely used for patients with HR+/HER2- advanced or metastatic breast cancer into the early-stage setting. It is very exciting to see the discoveries that have changed the standard of care (SOC) for patients with advanced disease now beginning to have an early impact on the treatment of patients with early-stage disease.

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In my opinion, the most exciting abstract at SABCS 2025 presented interim results from the phase 3 global lidERA trial (abstract GS1-10). This study, presented by Aditya Bardia, MD, MPH, and colleagues, evaluated the activity of the oral SERD giredestrant in the adjuvant setting for ER+/HER2- early-stage breast cancer. lidERA enrolled more than 4000 patients with stage I to III, high- or medium-risk ER+/HER2- breast cancer. Patients were randomized to receive either giredestrant or SOC endocrine therapy (ie, an aromatase inhibitor or tamoxifen). At close to 3 years of follow-up, the patients receiving giredestrant had a 30% lower risk of disease recurrence compared with those receiving SOC endocrine therapy, with an absolute benefit of 2.8% in reducing the risk of disease recurrence. Giredestrant was well tolerated with no substantial safety signals. In fact, compared with SOC endocrine therapy, fewer patients had to stop giredestrant due to joint side effects, which is a common problem in individuals receiving aromatase inhibitor therapy and a reason why patients may stop endocrine therapy prematurely.

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One limitation of lidERA is that CDK4/6 inhibitors were not included in the study. Many patients with stage II breast cancer—and almost all patients with stage III breast cancer—are candidates for adjuvant regimens that include both endocrine therapy and a CDK4/6 inhibitor (eg, abemaciclib or ribociclib). So, although lidERA is a positive trial, the implications may be complex. If giredestrant is approved by the US Food and Drug Administration (FDA), it will be important to determine the best candidates for this agent, given the potential overlap with indications for CDK4/6 inhibitor therapy. The lidERA trial is the first study in 25 years to show the superiority of a new endocrine agent in the adjuvant setting, so it really is groundbreaking and could be the beginning of a new age of adjuvant endocrine therapy for patients with breast cancer.

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Studies on ctDNA monitoring were also presented at this year’s SABCS meeting. ctDNA testing is increasingly being used in metastatic breast cancer, primarily to interrogate the tumor genome and identify the presence and/or absence of actionable mutations. Given the development of highly sensitive tests, there has been great interest in whether ctDNA also has value in the early-stage setting to evaluate for measurable residual disease.

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Data on ctDNA evaluation in HR+/HER2- early-stage breast cancer from the phase 3 PALLAS trial, which I colead, were presented at SABCS 2025 by Heather A. Parsons, MD, MPH, et al (abstract RF3-04). The PALLAS trial evaluated the CDK4/6 inhibitor palbociclib in the adjuvant setting in patients with stage II or III HR+/HER2- breast cancer, and serial ctDNA was collected prospectively from study participants. Overall, although most patients remained ctDNA negative post treatment, approximately 8% of patients were found to have detectable ctDNA at any time. Additionally, ctDNA-positive patients have had a significantly higher risk of cancer recurrence compared with ctDNA-negative patients. This observation has also been made in prior studies; however, having this validated within the context of a large study helps to confirm that ctDNA positivity is a prognostic biomarker in the early-stage disease setting.

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Although ctDNA allows us to identify high-risk patients, the challenge has been determining how to treat ctDNA-positive patients to improve their prognosis. At SABCS 2025, data from the exploratory phase 2 LEADER study, presented by Arielle J. Medford, MD, and colleagues, identified ctDNA-positive patients with ER+/HER2- early-stage breast cancer and treated them with the CDK4/6 inhibitor ribociclib (poster PD5-01). Among the 140 evaluable patients, 9 were ctDNA positive and received ribociclib treatment; one-third cleared ctDNA with the introduction of ribociclib. These findings from this small experience do not endorse using this treatment strategy in clinical practice, but they do support the concept that the introduction of an effective therapy may help change the course of disease for patients who are found to be ctDNA positive. However, until we have more data in the early-stage setting supporting effective treatment maneuvers, the use of ctDNA monitoring in this setting is discouraged.

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Finally, another exciting study presented at SABCS 2025 by my colleague, Ann H. Partridge, MD, MPH, looked at the web-based Young, Empowered & Strong (YES) mHealth tool to see if it would improve the quality of life (QOL) and overall sense of well-being for young breast cancer survivors (abstract GS3-03). Study participants completed online questionnaires about QOL, cancer-specific symptoms, and the impact of cancer on their health and outlook on life. Should a patient report specific symptoms, the YES platform automatically sent them information and education about symptom management and other supportive care tools. Patients who participated in the intervention reported a much greater improvement in their QOL scores compared with patients who were randomized to usual care. This study suggests that there are ways to harness the power of electronic systems and platforms to substantially improve support for our youngest patients with breast cancer and to help them with some of their most challenging symptoms without requiring significant clinical manpower. I think that it shows great promise and opens up many new opportunities to help support these patients.