Expert review of SABCS 2025 highlighting oral SERDs, HER2 strategies, ADCs, de-escalation trials, PROs, and AI in breast cancer care.
San Antonio Breast Cancer Symposium 2025 (SABCS 2025):
Plenary Evidence, Translational Advances, and Evolving Clinical Paradigms in Breast Cancer
(San Antonio, Texas, USA; December 9–12, 2025)
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Melisa Hunis MD |
Adrian Hunis MD |
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School of Medicine |
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Abstract
The San Antonio Breast Cancer Symposium 2025 (SABCS 2025) reaffirmed its status as the most influential meeting devoted exclusively to breast cancer research, with an emphasis on translational depth, clinically meaningful endpoints, and patient-centered evaluation [1–3]. Across plenary and late-breaking sessions, the program highlighted (i) next-generation endocrine strategies for early hormone receptor–positive disease, particularly oral selective estrogen receptor degraders (SERDs) [12,20]; (ii) optimization of HER2-positive metastatic disease through active maintenance intensification [9–11,24]; (iii) refinement of antibody–drug conjugate (ADC) positioning in endocrine-refractory HR+/HER2− advanced disease [16–18]; (iv) randomized evidence supporting de-escalation of preoperative imaging and axillary staging [14,15]; (v) emerging immunomodulatory combinations (including radiotherapy as an immune primer) for biologically “cold” tumors [27,28]; and (vi) multimodal artificial intelligence (AI) models capable of improving prediction of late distant recurrence [21,22,26]. This review integrates the principal themes of SABCS 2025 and provides detailed, clinically oriented analyses of selected plenary presentations—emphasizing methodology, effect size, toxicity/quality-of-life trade-offs, and practical implications for decision-making [25,26,30].
Keywords: SABCS 2025; breast cancer; oral SERD; HER2; maintenance therapy; antibody–drug conjugate; de-escalation; PROs; AI; late recurrence.
Introduction
The San Antonio Breast Cancer Symposium (SABCS) has, for decades, functioned as a bellwether for breast cancer science and practice—distinguished by its disease-specific scope, strong translational identity, and steady focus on endpoints that matter to patients and clinicians [1–3]. In 2025, the meeting again combined broad thematic coverage (prevention, biology, systemic therapy, local therapy, survivorship) with high-impact plenary presentations selected for their potential to shift standards of care or to clarify common areas of uncertainty in practice [3,19,23,24].
SABCS 2025 also reflected the current maturity of the field. Precision oncology is no longer defined solely by the availability of molecularly targeted agents; it is increasingly defined by the ability to deploy therapies and procedures with the right intensity, for the right duration, and in the right sequence—while avoiding unnecessary interventions that add toxicity, cost, or long-term morbidity without improving outcomes [19,23,24]. Two parallel narratives dominated the meeting: biology-driven intensification (where residual risk remains high) and evidence-based de-escalation (where more treatment does not translate into better results) [14,15,19].
Methods (narrative approach)
This article is a narrative, clinically oriented synthesis of SABCS 2025 content. Emphasis is placed on plenary sessions, late-breaking oral presentations, and formally released trial summaries/abstracts [1–3]. For each highlighted study, we summarize design, population, endpoints, key results, and limitations, and we provide a pragmatic interpretation of how the data might influence clinical practice. Where available, patient-reported outcomes (PROs) and quality-of-life measures are discussed alongside efficacy and safety, consistent with established PRO guidance and reporting standards [25,26,29,30].
Conceptual Summary: the four clinical “moves” emphasized in SABCS 2025
Across subtypes and stages, SABCS 2025 repeatedly returned to four practical “moves” that characterize modern breast oncology [19,23,24]:
1) Intensify smartly: add therapy when biology and risk justify it, and measure benefit with robust endpoints [6–9,20].
2) De-escalate confidently: omit tests or procedures when randomized evidence shows no improvement in outcomes [14,15].
3) Center the patient experience: treat PROs and long-term function as co-primary considerations, not afterthoughts [25,26,29,30].
4) Integrate data: combine pathology, clinical variables, genomics, and emerging AI to refine long-term risk—especially late recurrence in HR+/HER2− disease [21,22,26].
Plenary Session Analyses (in-depth, practice-oriented)
1. DESTINY-Breast09: patient-reported outcomes with T‑DXd + pertuzumab vs THP in 1L HER2+ a/mBC
New PRO data from DESTINY‑Breast09 examined how patients experience first-line treatment beyond traditional clinician-graded toxicity [4]. In this phase III program, patients with HER2-positive advanced/metastatic breast cancer were randomized in a 1:1:1 design to receive T‑DXd, T‑DXd + pertuzumab, or the established standard taxane + trastuzumab + pertuzumab (THP) [4,5]. The SABCS 2025 presentation focused on the comparison between T‑DXd + pertuzumab and THP, evaluating 383 and 387 patients, respectively, using validated instruments (EORTC QLQ‑C30, QLQ‑BR45, PRO‑CTCAE, and PGI‑TT) [4,6–8,25,29]. Assessments were performed each cycle through cycle 9 and then every two cycles until progression [4].
The central message was not that the regimens feel identical, but that the overall burden is comparable while the symptom “signature” differs [4,25,26]. Pain trajectories were similar in both arms: median time to deterioration in pain was not reached and the risk of worsening was essentially equivalent (HR ~0.95) [4]. This finding is clinically important because pain is a major driver of daily functioning and a common reason for emergent care in metastatic disease [25,26].
In symptom-specific analyses, T‑DXd + pertuzumab was associated with a higher early burden of gastrointestinal symptoms (nausea/vomiting, constipation, appetite loss) [4]. The differences diminished over time but did not fully disappear, suggesting that proactive antiemetic strategies and early supportive care remain crucial when selecting this regimen [4,25]. By contrast, THP produced comparatively more skin/mucosal complaints and certain PRO‑CTCAE signals such as epistaxis and peripheral edema [4,8]. These patterns are consistent with known class effects (chemotherapy-related mucositis/skin toxicity versus ADC-associated nausea) [16,25].
Importantly, global domains that matter to patients—physical function, fatigue trajectories, and overall tolerability as measured by PGI‑TT—were largely maintained and comparable across arms [4,25,26,30]. The practical implication is that, when efficacy is favorable for T‑DXd–based therapy, PROs support its use as a first-line option while clarifying the trade-off: more GI symptoms in exchange for less skin/mucosal burden, with broadly similar overall quality-of-life preservation [4,25,26].
Limitations include the intrinsic complexity of PRO interpretation across long treatment durations (missingness over time, informative dropout, and the challenge of attributing symptoms to disease versus treatment) [25,26,30]. Nonetheless, these data are highly actionable for counseling and supportive care planning [25,26].
2. HER2CLIMB‑05: tucatinib added to trastuzumab/pertuzumab maintenance after induction
HER2CLIMB‑05 reframed first-line management of HER2-positive metastatic breast cancer by treating maintenance therapy as an active, outcome-modifying phase rather than a passive continuation step [9]. Patients who completed 4–8 cycles of induction taxane + trastuzumab + pertuzumab without progression were randomized to tucatinib versus placebo while continuing trastuzumab and pertuzumab [9,10]. The primary endpoint was progression-free survival (PFS), with key secondary endpoints including overall survival and central nervous system (CNS) outcomes [9–11].
At SABCS 2025, the addition of tucatinib to maintenance was reported to prolong PFS by approximately 8.6 months, with consistent benefit across subgroups [9]. The CNS findings were clinically compelling: in patients with baseline brain metastases, tucatinib appeared to improve CNS control, reinforcing prior evidence of tucatinib activity in CNS disease [11,24]. In practical terms, the study supports a strategy of deepening HER2 blockade during maintenance to extend chemotherapy-free control—an outcome that is meaningful for quality of life, cumulative toxicity, and long-term treatment sustainability [9,11,25,26].
Key interpretive considerations include selection (randomization only after non-progression on induction), the maturity of OS at the time of reporting, and real-world tolerability when tucatinib is continued for extended durations [9–11]. Even with these caveats, HER2CLIMB‑05 contributes a clear message: for many patients, the maintenance phase is an opportunity to extend control without returning to cytotoxic therapy [9,24].
3. lidERA: adjuvant oral SERD giredestrant vs standard endocrine therapy in early HR+/HER2− breast cancer
The lidERA phase III trial addressed one of the most persistent problems in breast oncology: endocrine resistance and relapse in early HR+/HER2− disease [12]. Despite broad use of tamoxifen and aromatase inhibitors, residual risk—especially late recurrence—remains substantial [20,30]. Oral SERDs represent a mechanistically attractive evolution, aiming to degrade the estrogen receptor and overcome resistance pathways that limit the effectiveness of standard endocrine therapy [12,20].
In lidERA, giredestrant was compared with physician’s choice of standard adjuvant endocrine therapy in patients with stage I–III HR+/HER2− breast cancer after definitive local therapy (and chemotherapy when indicated) [12,13]. SABCS 2025 reporting indicated a statistically significant improvement in invasive disease-free survival (iDFS) with giredestrant [12]. The tolerability profile was consistent with endocrine therapy, with expected vasomotor symptoms and musculoskeletal complaints; attention was also given to low-grade bradycardia signals described with some agents in this class [12].
Clinically, these results are potentially paradigm shifting because they target the largest global breast cancer population in the curative setting [20,23,24]. If durability is confirmed with longer follow-up and if the benefit persists across risk strata, oral SERDs may become a new endocrine backbone in adjuvancy [12,20,24]. Practical next questions include optimal duration, combination with CDK4/6 inhibitors in high-risk disease, and the role of biomarker-guided escalation or de-escalation (including ctDNA-driven strategies) [23,24].
Broader High-Impact Themes Beyond the Plenary Core
Antibody–drug conjugates in HR+/HER2− advanced disease: sequencing lessons from ASCENT‑07
While enthusiasm for ADCs remains high, SABCS 2025 also emphasized the importance of rigorous sequencing data [16]. The ASCENT‑07 phase III study evaluated sacituzumab govitecan compared with physician’s choice chemotherapy as first chemotherapy after endocrine resistance in HR+/HER2− advanced breast cancer [18]. The reported PFS was similar between arms (median approximately 8.3 months in both groups), indicating that earlier use of this ADC in that particular clinical position did not yield a clear PFS advantage [18].
This result is clinically valuable even when not “positive.” It helps prevent premature migration of an effective later-line agent into an earlier slot without demonstrated benefit, and it underscores the need to individualize sequencing based on prior therapies, biomarker context, and competing options (including other ADCs and targeted agents) [16,17,19]. It also reinforces that toxicity profiles—particularly hematologic toxicity—must be weighed against incremental benefit when selecting ADCs [16,17].
De-escalation with randomized evidence: fewer tests and less surgery when outcomes are unchanged
A prominent SABCS 2025 message was that de-escalation is not a philosophical preference; it is an evidence-based strategy [14,15]. Two trials illustrate this clearly.
First, Alliance A011104/ACRIN 6694 evaluated routine preoperative breast MRI in selected patients with early-stage HR-negative breast cancer [14]. The trial reported no improvement in locoregional recurrence, distant recurrence, or overall survival with MRI added to standard imaging [14]. This supports a selective approach to MRI use, reducing cost, delays, and downstream biopsies without sacrificing control [14,19].
Second, BOOG 2013‑08 examined omission of sentinel lymph node biopsy in clinically node-negative patients treated with breast-conserving surgery and radiotherapy [15]. At approximately five years, regional control and survival outcomes were comparable between omission and standard approaches [15]. The implication is substantial: for appropriately selected patients, axillary staging can be safely minimized, reducing risk of lymphedema and chronic morbidity [15,23].
Together, these studies anchor a practical framework: de-escalate when (i) systemic treatment decisions are unlikely to change, (ii) local control is preserved by radiotherapy and modern systemic therapy, and (iii) morbidity reduction is meaningful [14,15,19,23].
Immunomodulation in HR+/HER2− disease: radiotherapy as an immune primer (P‑RAD)
SABCS 2025 also highlighted innovative strategies to make HR+/HER2− tumors more immunologically responsive [27]. The P‑RAD phase II program examined whether preoperative radiotherapy combined with pembrolizumab and chemotherapy could enhance antitumor immune activity [28]. The reported increase in tumor-infiltrating lymphocytes and improved preoperative response metrics support the concept that radiotherapy may serve as an immune primer in biologically “cold” tumors [27,28].
At present, this approach remains investigational and requires validation in larger studies with clinically meaningful endpoints [28]. Nonetheless, it reflects an important conceptual shift: rather than asking whether checkpoint blockade “works” in HR+/HER2− disease, researchers are increasingly asking how to alter the microenvironment to make immunotherapy more effective [27,28].
Artificial intelligence and multimodal prognostic modeling: better prediction of late recurrence
A distinctive feature of SABCS 2025 was the emphasis on multimodal prediction of long-term outcomes [21,22]. An AI model integrating digital pathology, clinical variables, and expanded molecular features—developed using data and biospecimens from major HR+/HER2− cohorts—was reported to outperform established genomic assays in predicting distant recurrence, particularly late recurrence beyond five years [21,22,26].
This is clinically consequential because late relapse is a defining challenge of HR+/HER2− disease and is a major driver of extended endocrine therapy decisions [20,21,30]. If validated prospectively and shown to improve clinical utility (not just statistical discrimination), such models could refine who benefits from extended therapy, who should receive escalation, and who can safely avoid overtreatment [21–24,26]. Implementation considerations include standardization of digital pathology workflows, external validation across diverse populations, and transparent performance reporting [26].
Table 1. Plenary trial highlights and practical takeaways [4,9,12]
Table 2. De-escalation studies: what can be safely omitted in selected patients [14,15]
Table 3. Practical synthesis by subtype and clinical question [19,23,24]
Figure 1
Figure 1. Conceptual model: post‑SABCS 2025 decision-making framework. Clinical decisions are organized into four sequential filters: (A) Biology and risk—subtype, stage, prior therapy, and residual risk determine whether intensification is justified [19,23,24]; (B) Evidence threshold—interventions are added only when randomized data show clinically meaningful benefit [6–9]; (C) Patient experience—PROs and long-term function guide choices between similarly effective options [25,26,29,30]; and (D) Data integration—genomics, pathology, and emerging AI refine long-term risk (especially late recurrence) and guide duration [21,22,26].
Discussion: what changes now, what changes later
SABCS 2025 produced several signals with near-term practice relevance. In HER2-positive metastatic disease, the concept of active maintenance is strengthened, aligning with patient priorities to minimize chemotherapy exposure while preserving control [9–11,25,26]. In early HR+/HER2− disease, SERD-based adjuvant strategies may soon reshape endocrine backbones, particularly if durability is confirmed and if patient selection can be optimized [12,20,23,24].
Equally important, SABCS 2025 reinforced that high-quality randomized evidence can justify omission of common interventions [14,15]. The MRI and SLNB de-escalation data reduce morbidity, prevent delays, and preserve quality of life; the key is careful selection and adherence to the conditions under which safety was demonstrated [14,15,19,23].
Finally, the meeting highlighted the future direction of personalized oncology: integrating multiple data modalities and emphasizing patient experience [21–26]. AI models that better capture late recurrence risk address a clinically significant gap in HR+/HER2− care and may eventually guide both escalation and extension strategies [20–24,26,30]. The next step is prospective validation with demonstrated clinical utility [26].
Conclusions
SABCS 2025 reflected a mature, pragmatic era of breast cancer research in which progress is measured not only by adding effective therapies, but also by reducing unnecessary interventions, improving patient experience, and refining long-term risk assessment [14,15,19,23–26]. Plenary evidence emphasized three practice-relevant themes: (i) quality-of-life informed deployment of highly active HER2-directed regimens [4,9–11,25,26]; (ii) active maintenance strategies that extend chemotherapy-free control [9–11]; and (iii) next-generation endocrine backbones with potential to reduce recurrence in early HR+/HER2− disease [12,20]. Together with de-escalation trials and multimodal AI innovations, these developments define a coherent roadmap for near-term guideline evolution and future research priorities [19,21–24,26].
References:
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