recent trails in locally advanced breast carcinoma
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"locally advanced breast cancer" AND trial
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"locally advanced breast cancer" AND neoadjuvant
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2024 2025 phase 3 trial locally advanced breast cancer neoadjuvant
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breast neoplasms AND pembrolizumab AND neoadjuvant
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breast neoplasms AND trastuzumab AND neoadjuvant
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triple negative breast neoplasms AND carboplatin AND neoadjuvant
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hormone receptor positive breast neoplasms AND neoadjuvant
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PMID: 39282906
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PMID: 39813643
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PMID: 39838117
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PMID: 41130363
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PMID: 37235845
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ESMO breast cancer 2025 locally advanced neoadjuvant KEYNOTE-522 KATHERINE guidelines
Recent pivotal trials relevant to locally advanced breast carcinoma
Locally advanced breast cancer (LABC) usually refers to non-metastatic stage III disease, treated with curative intent using neoadjuvant systemic therapy, surgery, and regional radiotherapy. Modern trials commonly enroll stage II-III “high-risk early breast cancer,” so their results are directly relevant to many patients with LABC. Standard principles remain neoadjuvant therapy to downstage breast and axilla, followed by surgery and radiation. Current Surgical Therapy, p. 780.
| Subtype / setting | Trial and result | Practical implication |
|---|---|---|
| Triple-negative breast cancer (TNBC), stage II-III | KEYNOTE-522, phase III: neoadjuvant pembrolizumab plus carboplatin-taxane followed by anthracycline/cyclophosphamide, then adjuvant pembrolizumab. At 5 years, overall survival was 86.6% vs 81.7% with chemotherapy alone (P = .002). Schmid et al., 2024, PMID 39282906 | Perioperative pembrolizumab with chemotherapy is a standard option for high-risk stage II-III TNBC, including LABC, if there is no contraindication to immunotherapy. Monitor immune-related toxicity. |
| TNBC, platinum component | BrighTNess long-term phase III follow-up supported carboplatin as part of neoadjuvant therapy, improving pCR without convincing added benefit from veliparib. Geyer et al., 2022, PMID 35093516 | Carboplatin is commonly incorporated into the neoadjuvant backbone for high-risk TNBC, particularly alongside the KEYNOTE-522-type regimen. |
| HER2-positive disease with residual invasive tumor after neoadjuvant treatment | KATHERINE final survival analysis: adjuvant T-DM1 for 14 cycles vs trastuzumab. At 7 years, invasive disease-free survival was 80.8% vs 67.1%, and overall survival 89.1% vs 84.4%; HR for death 0.66. Geyer et al., 2025, PMID 39813643 | If residual invasive HER2-positive disease remains in breast or nodes after preoperative anti-HER2 therapy, escalate postoperative therapy to T-DM1, rather than continuing trastuzumab alone. |
| HER2-positive, high-risk stage II-III disease | DESTINY-Breast11, phase III: neoadjuvant trastuzumab deruxtecan followed by paclitaxel-trastuzumab-pertuzumab (T-DXd-THP) produced pCR 67.3% vs 56.3% with dose-dense AC-THP. Grade 3 or higher toxicity was also lower with T-DXd-THP. Event-free survival data remain immature. Harbeck et al., 2026, PMID 41130363 | A major emerging regimen. It improves pCR, but mature EFS and OS data, regulatory status, and safety considerations, especially interstitial lung disease risk with T-DXd, determine whether it replaces established chemotherapy plus trastuzumab-pertuzumab in routine care. |
| High-risk ER-positive/HER2-negative disease | KEYNOTE-756, phase III: adding pembrolizumab to neoadjuvant chemotherapy improved pCR from 15.6% to 24.3%. Event-free survival was not mature at reporting. Grade 3 or higher treatment-related adverse events were 52.5% vs 46.4%. Cardoso et al., 2025, PMID 39838117 | Promising pCR signal, but pembrolizumab is not yet established standard treatment for unselected ER-positive/HER2-negative LABC until mature survival outcomes and guideline decisions are available. |
| Staging of LABC | PETABC, randomized trial: baseline FDG-PET/CT upstaged 23% to metastatic disease vs 11% with conventional CT plus bone scan, changing management in many upstaged patients. Dayes et al., 2023, PMID 37235845 | PET/CT can prevent inappropriate curative multimodality treatment in selected stage III or high-risk stage IIB patients by finding occult metastatic disease. |
Current subtype-based treatment approach
- TNBC: Neoadjuvant chemotherapy with pembrolizumab for stage II-III high-risk disease, then surgery, radiotherapy, and completion of adjuvant pembrolizumab when appropriate. Residual disease may prompt additional risk-directed adjuvant therapy depending on germline BRCA status and prior treatment.
- HER2-positive LABC: Neoadjuvant chemotherapy plus trastuzumab and pertuzumab remains a widely used standard. Pathologic complete response generally permits completion of HER2-directed therapy; residual invasive disease indicates adjuvant T-DM1.
- ER-positive/HER2-negative LABC: Neoadjuvant chemotherapy is used when tumor burden, grade, nodal status, or biology indicates chemotherapy benefit. Neoadjuvant endocrine therapy is an option for selected strongly hormone-sensitive tumors, particularly in postmenopausal patients or those unsuitable for chemotherapy. Adjuvant endocrine therapy is essential.
Take-home points
- The biggest established recent advance is perioperative pembrolizumab for stage II-III TNBC, now with an overall-survival benefit.
- For HER2-positive disease, response-adapted postoperative treatment is central: residual disease should lead to T-DM1.
- T-DXd-based neoadjuvant therapy is an important emerging HER2-positive strategy, but long-term outcomes are still immature.
- Immunotherapy in ER-positive/HER2-negative LABC remains investigational outside selected trial contexts.
- LABC should be managed by a multidisciplinary breast team, with receptor testing, germline testing when indicated, systemic staging, and planned surgery-radiation sequencing from the start.
Recent evidence can update older textbook pathways, particularly for TNBC immunotherapy and HER2-positive response-adapted therapy.
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