SABCS 2025 Session Makes Sense of Rapidly Evolving Therapeutic Landscape for Breast Cancer 

December 22, 2025 by

A recurring sentiment expressed at the San Antonio Breast Cancer Symposium (SABCS) 2025 was that the incredible advances reported during the conference means that there may soon be multiple, highly effective options available to treat various types and stages of breast cancer. 

With all of these choices, what should a physician do back in their clinic come Monday morning? 

As has become SABCS tradition, a panel of breast cancer experts explored this question during the conference’s closing session, “View From the Trenches: What to Do on Monday Morning.” To put the latest findings into context and help clinicians navigate the rapidly evolving therapeutic landscape, panelists dissected the ins and outs of how they would apply the newly reported data in their own practices. 

The panel discussion was moderated by Heather McArthur, MD, of UT Southwestern. Additional panelists included: 

Six panelists, including a patient advocate, weighed in on the clinical implications of advances reported during SABCS 2025.

Metastatic Breast Cancer 

Expanding First-line Options May Enable Individualized Treatment Approaches for Metastatic HER2-positive Disease 

McArthur pointed out that in just one year, three new treatment regimens have shown promise for newly diagnosed, human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer: 

  • tucatinib (Tukysa) in combination with trastuzumab (Herceptin) and pertuzumab (Perjeta) for maintenance therapy, which led to improved progression-free survival (PFS) data in the HER2CLIMB-05 trial reported at this year’s SABCS; 
  • trastuzumab deruxtecan (T-DXd; Enhertu) plus pertuzumab, supported by PFS data from DESTINY-Breast09 reported earlier this year (and which was approved by the U.S. Food and Drug Administration shortly after SABCS 2025 ended); and 
  • palbociclib (Ibrance) combined with anti-HER2 and endocrine therapy, which demonstrated PFS benefit in the PATINA trial that was reported last year at SABCS 2024. 

“This has been a very exciting area of drug development,” said McArthur. Given the many options that may soon be available for the first-line treatment of metastatic HER2-positive breast cancer, McArthur asked panelists if they thought there was an optimal first-line therapy for metastatic HER2-positive breast cancer. 

Jhaveri responded that there is unlikely to be a “one-size-fits-all approach” for this patient population and that the growing number of options may instead allow for a more individualized treatment approach that accounts for hormone receptor (HR) status and the extent and location of metastases.  

She explained that she would likely recommend the PATINA regimen for patients with HR-positive disease and limited disease burden, and the DESTINY-Breast09 regimen for patients who have HR-negative disease and/or metastasis to the brain or other critical organs. 

As far as the tucatinib-based maintenance therapy tested in HER2CLIMB-05, Jhaveri expressed some concerns with the findings. She pointed to the 16-month median PFS in the control arm in HER2CLIMB-05 as oddly low given that 70% of the population had de novo metastatic disease, noting that similar patient populations have experienced median PFS of 26 to 29 months in other clinical trials. The median PFS was even lower (approximately 12 months) for the HR-negative subpopulation. 

While the control arm results were “strikingly distinct,” Jhaveri anticipates that, someday, tucatinib-based maintenance therapy could still have a place in the first-line treatment of HER2-positive metastatic breast cancer.  

Komal Jhaveri, MD, PhD, and Lajos Pusztai, MD, DPhil, discussed emerging treatment options for metastatic breast cancer. 

“I do think that we are moving towards a place where we will do some upfront therapy and some maintenance, and that will depend on [HR status] based on the data that we’ve seen,” Jhaveri said. 

Pusztai agreed: “There’s a lot of personal details that go into selecting a treatment regimen for an individual person, but assuming an average person in otherwise good health, it’s clear from this study, that for the HR-negative, HER2-positive patients, the HER2CLIMB regimen is more effective than just giving them [trastuzumab] and pertuzumab.”  

For HR-positive breast cancers, he reminded attendees that patients receiving the HER2CLIMB-05 triplet regimen would actually receive a total of four maintenance drugs since they would also need to receive hormone therapy. He cited this as one of the reasons he would favor the PATINA regimen for HR-positive breast cancers. 

Jhaveri noted that it would be nice to understand how the different regimens might fit together, and whether it would be feasible to use the DESTINY-Breast09 T-DXd regimen as upfront induction therapy, followed by the tucatinib-based maintenance therapy from HER2CLIMB-05 for patients with HR-negative disease. 

“But so far, we just have these three distinct datasets,” she said.   

Pusztai, however, argued that findings could be extrapolated across the studies. “I think it’s perfectly reasonable to assume that T-DXd would be a really good induction therapy,” he said. You treat the patient for six to eight cycles … and then you switch to the maintenance therapy, which is definitely better tolerated than additional cycles of T-DXd.” 

Updated Data Support Efficacy of Oral SERDs in Metastatic HR-positive Disease Regardless of ESR1 Mutation Status 

For the second-line treatment of HR-positive, HER2-negative metastatic breast cancer, two endocrine therapy regimens continued to show efficacy, according to updated analyses presented at the meeting. 

At last year’s SABCS, Jhaveri reported primary efficacy results from the EMBER-3 clinical trial, which showed PFS improvements with the oral selective estrogen degrader (SERD) imlunestrant monotherapy in patients with previously treated HR-positive, HER2-negative advanced cancers that harbored ESR1 mutations. When combined with abemaciclib (Verzenio), imlunestrant improved PFS regardless of ESR1 mutation status. Data from the trial led to the September 2025 approval of imlunestrant monotherapy under the brand name Inluriyo.  

This year, Jhaveri shared updated PFS data that showed that, after an additional 14 months of follow-up, the imlunestrant-abemaciclib combination continued to improve PFS regardless of ESR1 mutation.  

In addition, new subgroup analyses from the evERA trial suggested that a regimen that combined the oral SERD giredestrant with everolimus (Afinitor) also extended PFS regardless of ESR1 mutation status.  

In light of the positive results of these regimens for both ESR1-mutated and ESR1 wild-type breast cancers, McArthur asked whether there was still a place for biomarker profiling. 

“What a great question,” said Jhaveri. “We went from … saying that we need to do biomarker testing, and we’re now seeing benefit regardless of [the biomarker]. Should we stop doing it? The short answer is no.” 

She explained that even though alterations in the target may not impact efficacy, biomarker testing can still provide information about other genes that can help predict prognosis and guide treatment decisions, including for subsequent lines of therapy. 

Jhaveri also emphasized the importance of the shared decision-making process when choosing between the imlunestrant-abemaciclib and giredestrant-everolimus regimens, highlighting that differences in toxicity and dosing schedules, among other factors, may inform which one is ultimately prescribed. 

DCIS and Early-stage Invasive Breast Cancer 

After Two Decades, a New Adjuvant Endocrine Therapy Shows Promise for Early-stage Breast Cancer  

Potentially practice-changing results from the lidERA trial made “quite a bit of buzz during the meeting,” said McArthur, referring to findings that giredestrant lowered the risk of invasive disease progression by 30% in patients with stage 1-3 HR-positive, HER2-negative breast cancer, compared with standard endocrine therapy. 

While oral SERDs, including giredestrant, have shown activity in the metastatic setting, McArthur noted that “these are the first positive data for an oral SERD in the adjuvant setting,” and “the first improvement in adjuvant endocrine therapy that we’ve seen in 20 years.”  

Heather McArthur, MD, moderated the “View From the Trenches: What to Do on Monday Morning” session. 

“I think this is wonderful news,” said Pusztai. “I would love to use this drug in everybody.”  

He compared the magnitude of improvement to that seen with the addition of ovarian suppression in the landmark SOFT and TEXT trials, and he highlighted that giredestrant’s toxicity profile was similar to standard care. The big remaining question, he said, is how much the drug will cost. 

“If this drug costs a small amount of money, then I think we could use it in everybody,” he said. 

Jhaveri agreed that giredestrant shows potential for broad utility, and she expects that results from a subgroup of patients who also received abemaciclib will help clinicians better understand how giredestrant might fit into the existing therapeutic landscape of early-stage HR-positive breast cancer. 

New Findings Will Inform Decisions About Treatment De-escalation and Escalation  

Treatment de-escalation was another major theme at SABCS, with results providing new insights into the omission of breast or lymph node surgery for certain patients. 

In the LORETTA trial, patients with low-risk, HR-positive, HER2-negative ductal carcinoma in situ (DCIS) received tamoxifen alone—without surgery—and had low rates (9.8%) of five-year invasive breast cancer. While the study did not meet its primary endpoint, McArthur noted that it adds to growing research, including results from the COMET trial reported at SABCS last year, on treatment de-escalation for DCIS.  

“Imaging is advancing our ability to detect [DCIS],” said Boughey. “We need to continue to evolve how we manage it.” 

McArthur asked panelists whether they would feel comfortable with skipping surgery and using tamoxifen alone for patients with low-risk DCIS based on this study. 

“This really comes back to shared decision-making,” said Boughey. “But ultimately, LORETTA was a negative trial …  I think this underscores surgery still has a role in DCIS.”  

Despite the negative results, the trial adds important data that physicians and patients can consider together when making treatment decisions, Boughey said. Some patients may be comfortable with the 9.8% risk of invasive recurrence without surgery, while others might prefer to proceed with surgery, which Boughey explained tends to be a small lumpectomy with good cosmetic outcomes.  

McArthur raised the widespread issue of poor treatment adherence with hormone therapy, asking Maues, a patient advocate, how physicians could help improve compliance with these regimens, which become even more important if surgery is omitted. 

“I think the whole team plays a big role with different [clinicians] on the team talking with the patient and explaining the importance of the treatment and what the consequences could be of not following it,” said Maues.  

Julia Maues brought the patient perspective to the discussion. 

Jhaveri added that new treatments that help with the side effects of hormone therapy may also help improve adherence, and Pusztai emphasized the physician’s role in determining whether a patient’s symptoms are indeed due to the hormone therapy. 

He explained that hormone therapy can be safely paused for three months to see if doing so improves the patient’s symptoms. “Oftentimes, the symptoms don’t go away, and they don’t change after resuming the treatment,” he said. “That helps an individual come to terms that there are other things that may be causing a particular problem.” 

The panelists also discussed the implications of two studies, INSEMA and BOOG 2013-08, that examined the potential to de-escalate lymph node surgery in certain patients.  

In the intent-to-treat population of INSEMA, patients with early-stage, limited node-positive breast cancer who received either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) had similar five-year rates of disease recurrence and overall survival, suggesting that the less invasive SLNB procedure was as effective as ALND. In BOOG 2013-08, patients with early-stage, clinically node-negative, HR-positive, HER2-negative breast cancer experienced similar rates of five-year recurrence and survival whether or not they underwent SLNB, suggesting that, for certain patients, it may even be safe to omit all forms of lymph node surgery. 

“I think it’s really encouraging to see further datasets validating some of the advances that we’ve had over the last decade in terms of substituting, essentially, sentinel lymph node surgery [with] axillary ultrasound,” said Boughey.  

But since information from SLNB is often used to guide radiation, said McArthur, how might radiologists decide on treatment if SLNB were omitted? 

“I’m coming around to the idea that in the right patients, when we do good imaging, a clinically node-negative patient is kind of the equivalent of a pathologically node-negative patient from a SLNB,” said Strauss.  

Boughey noted that “the biggest challenge is that we need to make sure that de-escalating surgery doesn’t inadvertently result in escalation of radiation therapy.” She emphasized the need for studies evaluating the omission of both SLNB and radiation in this population. 

Panelists agreed that a key part of shared decision-making is careful consideration of the risks and benefits of treatment de-escalation or escalation. When treatments are omitted, patients might experience a higher quality of life but could potentially face a greater risk of disease progression. 

Jonathan Strauss, MD, and Judy Boughey, MD, discussed the potential of surgical de-escalation for early-stage breast cancers. 

Maues noted that physicians can help support patients who might blame themselves if they experience disease recurrence after opting for a less aggressive treatment—by emphasizing, for example, that patients are making the best decision with the information they have at that moment. 

On the flip side, when certain treatments are included, patients might have longer survival but experience additional toxicities—as has been seen with certain chemotherapeutics. For example, results from RJBC-1501 and a pooled analysis of BrighTNess, CALGB 40603, and GeparSixto highlighted the survival benefit of adding carboplatin to either neoadjuvant or adjuvant chemotherapy for patients with early-stage triple-negative breast cancer.  

“I think these studies collectively settled the question about the efficacy of adding carboplatin to an anthracycline and taxane regimen,” said Pusztai. “Unfortunately, the carboplatin brings in toxicities.”  

While the addition of carboplatin led to greater rates of hematologic toxicity, it did not impact quality of life or increase the rates of febrile neutropenia or peripheral neuropathy in these studies. Pusztai, however, expressed concerns that these data may not represent real-world experiences, noting that “anybody who has received carboplatin … can tell that this does add toxicity.” 

He said the decision of whether or not to include carboplatin will depend on the patient’s risk tolerance and ability to withstand toxicities, but he would favor starting with carboplatin in light of these data. “I think one reasonable strategy is to start with the most effective treatment, and if you have issues with it and your risk is low, then you can stop it,” he suggested. 

Similarly, adding a radiation boost to low-risk DCIS treatment improved outcomes but introduced additional toxicities, according to results from the Big 3-07/TROG 07.01 trial. 

Maues noted, “It all comes down again to communication, explaining [to patients] what these side effects are, what to watch for. Sometimes patients are afraid to tell their doctor that something is happening in fear of being taken off a treatment that might be working.”

For those who have registered for the symposium, sessions may be viewed on the SABCS virtual platform through March 31, 2026.