Early Breast Cancer New Information from San Antonio Breast Cancer Conference 2025

Adjuvant endocrine therapy is evolving:
Oral SERD in early HR+ / HER2− disease:
- lidERA (giredestrant vs standard endocrine therapy):
  - What it tested:
    - Adjuvant giredestrant (oral SERD) vs standard endocrine therapy after surgery in ER+ /HER2− early breast cancer
- Headline result:
  - Significant iDFS improvement:
    - They reported ~30% relative risk reduction (HR ~0.70) vs standard ET
  - Why it matters:
    - First credible signal in a long time that “better endocrine backbone” (beyond AI / tamoxifen) could become standard for selected early HR+ patients:
      - Especially if subgroup and safety data remain favorable
  - Surgical implication:
    - Expect more conversations about systemic escalation / de-escalation:
      - For example who truly needs CDK4/6 inhibitors vs a more potent endocrine option
Post-neoadjuvant HER2+ residual disease:
T-DXd moves earlier:
- DESTINY-Breast05 (T-DXd vs T-DM1):
  - Population:
    - HER2+ early breast cancer with residual invasive disease after neoadjuvant therapy:
      - High-risk post-NAC setting
  - Key outcome:
    - T-DXd superior to T-DM1 for invasive disease-free outcomes
  - Reported data (NEJM / PubMed):
    - Events 6.4% vs 12.6%, HR 0.47:
      - With 3-year DFS 92.3% vs 83.5%
  - Why it matters:
    - This is a direct “KATHERINE-successor” story:
      - If adopted into guidelines / pathways, it could reset the post-neoadjuvant standard for residual HER2+ disease
  - Surgical implication:
    - Reinforces the importance of accurate residual disease documentation (pathology, RCB, nodal status) because this is what triggers the post-NAC systemic pathway
Axillary de-escalation:
Omitting SLNB in selected cN0 patients:
- Dutch randomized trial (BOOG 2013-08):
  - Design:
    - Clinically node-negative (cT1 to cT2), treated with BCS + whole-breast RT, randomized to SLNB vs omission
  - Message:
    - Regional control / oncologic outcomes were not worse with omission in carefully selected patients, supporting a further step in axillary de-escalation
  - SABCS:
    - Also highlighted interpretation alongside RT fields (since RT contributes to axillary control)
- Practical “surgeon filter”:
  - This is not “no axillary surgery for everyone,” but it strengthens the discussion for:
    - Older / low-risk, cN0, BCS+RT patients in centers that can replicate selection / imaging rigor
Pre-op staging MRI:
- Routine use questioned in specific early BC subsets:
  - Alliance A011104 / ACRIN 6694:
    - Population:
      - Stage I / II HR-negative early breast cancer
    - Result:
      - Routine pre-op MRI did not improve key oncologic outcomes
      - MD Anderson reported 5-yr locoregional recurrence 6.8% with MRI vs 4.3% without (not favoring MRI)
    - Message:
      - More evidence that routine MRI may not improve outcomes and can drive additional procedures
    - Surgical implication:
      - Helps justify a more selective MRI strategy, dense breasts, lobular carcinoma, occult primary, discordant imaging, suspected multicentric disease, rather than reflex MRI for all
Immune priming concept:
- Preoperative RT + pembrolizumab
  in HR+ / HER2− (early signal):
  - TBCRC-053 (P-RAD):
    - Concept:
      - Short-course preoperative RT (e.g., 24 Gy / 3 fractions) added to pembrolizumab + chemotherapy
  - Signal:
    - Increased tumor T-cell infiltration and “immune activation” endpoints:
      - Hypothesis-generating but compelling
  - Clinical implication:
    - Not practice-changing yet, but it’s a blueprint for future trials aiming to convert HR+ tumors into more immunogenic disease
DCIS de-escalation reality check:
Tamoxifen-only (no surgery) did not meet safety bar:
- LORETTA (JCOG1505):
  - Design:
    - Single-arm tamoxifen without surgery for selected low-risk ER+ / HER2− DCIS
  - Outcome:
    - Reported 5-year ipsilateral invasive events exceeded prespecified safety threshold (widely summarized from SABCS)
  - Takeaway:
    - Supports continued caution:
      - Endocrine-only, surgery-free DCIS management should remain investigational / exceptional rather than broadly adopted
What to say at tumor board (tight synthesis) HR+/HER2−:
- LidERA:
  - Suggests a credible pathway toward next-generation endocrine therapy (oral SERD) in early disease
- HER2+ residual disease post-NAC:
  - T-DXd > T-DM1 in DESTINY-Breast05 – likely a major sequencing shift as pathways update
- Surgery de-escalation:
  - Growing evidence that less axillary surgery and less routine MRI can be safe in well-defined populations
- Translational front:
  - Preoperative RT + IO is an emerging strategy to watch, not a standard yet
- DCIS:
  - Surgery-free endocrine-only strategies still struggle with invasive recurrence risk thresholds