Breast Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology
- Study type
- Clinical guideline
- Study name
- NCCN Breast Cancer v4.2026
- Design
- Clinical guideline of the US National Comprehensive Cancer Network (NCCN); category 1 = high-level evidence and uniform consensus; category 2A = lower-level evidence and uniform consensus
- Source
- J Natl Compr Canc Netw · 2026
In plain words
The NCCN guidelines are among the most widely cited cancer treatment guidelines in the world. This version (4.2026) focuses on the treatment of metastatic breast cancer and tailors the choice of treatment to the tumour type (hormone-positive, HER2-positive, HER2-low, triple-negative), gene mutations (such as BRCA, PIK3CA and ESR1) and previous treatments.
Key guideline recommendations
- Category 1 / 2A, preferred
Pertuzumab + trastuzumab with a taxane (THP), followed by maintenance pertuzumab + trastuzumab, is the preferred first-line option for HER2-positive metastatic breast cancer (with docetaxel: category 1; with paclitaxel: category 2A).
- Other recommended options
In the NCCN panel's view, THP remains the preferred approach for most patients with untreated HER2-positive metastatic breast cancer, and trastuzumab deruxtecan + pertuzumab (based on DESTINY-Breast09) is included as an “other recommended option”; because of the risk of interstitial lung disease/pneumonitis, regular monitoring is recommended.
- Category 1, preferred / category 2A
Based on DESTINY-Breast04, trastuzumab deruxtecan is a preferred option for HER2-low metastatic breast cancer (IHC 1+ or 2+ with negative ISH); for HER2 IHC 0+ (based on DESTINY-Breast06, which has not yet shown an overall survival benefit) it is an “other recommended option”.
- Category 1, preferred
For patients with a PIK3CA-activating mutation and recurrence during or within 12 months after adjuvant endocrine therapy, fulvestrant/inavolisib/palbociclib is the preferred option (based on INAVO120).
- Category 1
If a CDK4/6 inhibitor has not been used previously, fulvestrant with a CDK4/6 inhibitor (abemaciclib, palbociclib or ribociclib) is recommended in the second or later line for HR-positive/HER2-negative breast cancer.
- Category 1, preferred
In patients with a germline pathogenic BRCA1/2 variant, treatment with a PARP inhibitor (olaparib or talazoparib) may be considered in the first line for endocrine-refractory HR-positive/HER2-negative disease.
- Category 1 / 2A
In metastatic TNBC with PD-L1 CPS below 10 and no germline BRCA1/2 mutation, first-line options include sacituzumab govitecan (category 1, preferred), datopotamab deruxtecan (category 2A, preferred) or chemotherapy (category 2A).
- Category 1, preferred
Capecitabine/tucatinib + trastuzumab is a preferred option in HER2-positive patients with systemic and brain progression in the third line and beyond, and may also be given in the second line.
Study population
Patients with recurrent or stage IV (metastatic) breast cancer; treatment strategies based on tumour biology (hormone receptor status and HER2 expression) and clinical factors such as prior therapy and disease-free interval.
Clinical significance and place in guidelines
The most up-to-date comprehensive guideline available, reviewing data from DESTINY-Breast09, DESTINY-Breast06, ASCENT-03, ASCENT-04 and INAVO120. Key point: despite better PFS in DESTINY-Breast09, NCCN still considers THP the preferred first-line therapy for most HER2-positive patients because of pulmonary toxicity and the lack of crossover.
Limitations
The NCCN guideline is based on the US health system, and access to drugs differs in other countries. The version published in the journal covers only the metastatic disease section; the algorithms are updated on the NCCN website.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.