ESMO Breast 2026: New Directions in Breast Cancer Treatment — Key Points Summary
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ESMO Breast 2026 reflects a new direction in breast cancer treatment, entering the era of Precision and Adaptive Breast Cancer Care. This focuses on reducing chemotherapy in suitable patients, selecting drugs based on biomarkers and genomic profiles, strategically using ADCs, applying ctDNA, and prioritizing patient quality of life. — Summary and analysis of 9 key points by Assoc. Prof. Dr. Yaowanuch Kongdan, President of the Thai Breast Cancer Society (TBS) and Director of Numarak Hospital.
A new direction in breast cancer treatment: more precise treatment, less chemotherapy, and improved quality of life.
The ESMO Breast 2026 conference reflected an overview of the new era of breast cancer treatment, which is shifting from "broad disease-type-based treatment" to a more disease-biologically-based approach. This involves systematically incorporating data from biomarkers, genomic profiles, ctDNA, treatment response, and patient quality of life into decision-making.
The key takeaways this year can be summarized as follows: breast cancer treatment approaches are moving towards reducing chemotherapy use in suitable patients, more accurate biomarker-based drug selection, more strategic use of ADCs, and the incorporation of ctDNA as a risk assessment tool, although it is not yet ready for general standardization in all cases.
1. Key Overview: Less Chemotherapy, More Precision
A key concept emerging from ESMO Breast 2026 is that breast cancer treatment isn't solely focused on "increasing the strength of treatment," but rather on selecting treatments that are appropriately tailored to each patient's risk profile.
Main point:
Reduce chemotherapy in appropriate patients — especially HER2-positive early breast cancer and some HR+/HER2– groups.
Use biomarkers for navigation — such as ESR1, PIK3CA, AKT1, HER2-low, PD-L1, BRCA.
Sequence ADCs carefully — as data on cross-resistance is emerging, particularly with TOPO1 ADCs following other TOPO1 ADCs.
ctDNA is beginning to play a role — being used to assess the risk of recurrence — but it should still be included in research or protocols with clear monitoring.
Focus on quality of life — especially for patients in the early stages, younger patients, and long-term survivors.
2. HR+/HER2– Group: The Era of Endocrine Precision Oncology
HR-positive/HER2-negative breast cancer remains the most common type, and treatment is shifting from traditional endocrine therapy to drug selection based on molecular mechanisms.
Initial stage: Adjust endocrine therapy according to risk.
In the early-stage HR+/HER2– group, risk assessment becomes more important, especially the use of data such as:
Ki-67
Genomic signatures such as Oncotype DX, MammaPrint
Clinical risk factors include nodule size and lymph node grade.
ctDNA in certain research contexts.
The overall approach is that low-risk patients may receive endocrine therapy alone, while moderate to high-risk patients may consider adding a CDK4/6 inhibitor or intensified adjuvant therapy as appropriate.
Data from ESMO Breast 2026 also highlights the role of oral SERDs , such as giredestrants, which have interesting anti-proliferative activity data, especially in younger or premenopausal women. However, their practical use still needs to be considered based on indications and approval data of each country.
Disseminated stage: Treatment depends on the mutation after CDK4/6 inhibitor use.
In metastatic HR+/HER2– disease, the key issue is treatment after developing resistance to CDK4/6 inhibitors, with biomarker testing playing an increasingly important role.
ESR1 mutation — Oral SERD
PIK3CA mutation — PI3K pathway inhibitor combined with endocrine therapy.
AKT1 alteration — AKT inhibitor
HER2-low — Consider ADCs as indicated.
There are no actionable biomarkers —other endocrine strategies, mTOR inhibitors, or clinical trials.
The key point is that treatment should no longer be a "one-size-fits-all" approach, but should move towards greater precision endocrine oncology.
3. HER2-Positive: Reduced chemotherapy in patients who respond well.
In the HER2-positive breast cancer group, the key direction is to try to reduce the treatment burden in patients who respond well, while maintaining the highest possible cure rate.
Initial phase: pCR-Guided Strategy
Data from PHERGain-2 support the concept of a response-adapted strategy , or adjusting treatment based on the disease's response. Specifically, patients with good responses may have the opportunity to reduce chemotherapy or adopt a chemo-sparing approach in the future.
However, caution is still needed on this issue, as not all HER2-positive patients are suitable for reducing the intensity of treatment. Patient selection must consider risk factors, disease stage, tumor biology, and response to neoadjuvant therapy.
Metastatic phase: T-DXd remains a key drug.
In metastatic HER2-positive disease, trastuzumab deruxtecan, or T-DXd, continues to play a crucial role in early-line therapy. The challenges remain: "how to treat after T-DXd" and "how to prioritize ADCs for optimal benefit."
The SATEEN study evaluating sacituzumab govitecan in combination with trastuzumab after T-DXd resistance showed promising signals, but they are not yet considered a new, generally applicable standard.
4. Triple-Negative Breast Cancer: Immunotherapy and ADCs are the core components.
In triple-negative breast cancer (TNBC), treatment remains complex due to the disease's aggressiveness and high biological diversity.
Initial stage: Chemo-immunotherapy remains the standard.
For early-stage TNBC, the neoadjuvant chemotherapy combined with immunotherapy approach remains the key standard, particularly guidelines similar to KEYNOTE-522.
The question being asked is: in patients who have achieved a pathologic complete response (pCR) , how much additional adjuvant therapy is needed, and can some of the treatment be reduced?
Residual Disease: A systematic treatment plan is required.
For patients with residual disease after neoadjuvant therapy, possible approaches to consider include:
Capecitabine
PARP inhibitor in patients with BRCA mutation.
ADCs in the context of clinical trials.
Evaluating ctDNA to assess the risk of molecular residual disease.
Metastatic stage: Selected based on PD-L1, BRCA, and treatment history.
In metastatic TNBC, treatment approaches are becoming more fragmented based on biomarkers.
PD-L1 positive — immunotherapy combined with chemotherapy.
BRCA mutation — PARP inhibitor
After receiving multiple immunotherapy or chemotherapy treatments — ADCs such as sacituzumab, govitecan, or datopotamab deruxtecan — should be used as indicated and based on available information.
HER2-low TNBC — HER2-targeted ADCs may be considered in some cases.
The key takeaway is that ADCs are becoming the primary tool in metastatic TNBC, but their selection must consider the drug sequence, payload mechanism, and cross-resistance risk.
5. HER2-Low and HER2-Ultralow: New Frontiers of HER2-Targeted Therapy
One of the key themes this year is the concept that HER2 isn't just "positive" or "negative," but rather a spectrum ranging from HER2-positive, HER2-low, to HER2-ultralow.
The HER2-low and HER2-ultralow groups are important because patients previously classified as HER2-negative may benefit from certain HER2-targeted ADCs, particularly in HR+ disease and some TNBC groups.
Areas for further improvement:
Clarify the definition of HER2-ultralow.
Consistency of IHC readings.
Reproducibility among pathologists.
Grading ADCs in patients who have previously received ADCs.
Selecting the most suitable patient.
In summary, HER2-low is not a completely new subtype, but rather a therapeutic category that expands the possibilities for treatment with ADCs.
6. ADC Sequencing: It's not just about changing the target, but also understanding the payload.
Antibody-drug conjugates (ADCs) were one of the most talked-about topics at this year's conference, particularly the question of how ADCs can be used against other ADCs.
Emerging evidence suggests that using TOPO1 ADC after a patient has previously received TOPO1 ADC may present cross-resistance issues; that is, even with different antibody targets, similar payloads or mechanisms of action may reduce efficacy.
Therefore, future ADC ranking should consider at least three aspects:
Target — e.g., HER2, TROP2, HER3
Payload — such as a TOPO1 inhibitor or other mechanism.
History of previous medication use — to assess the likelihood of cross-reactivity.
This concept is important for planning treatment for patients with metastatic disease, especially those already receiving multiple treatments.
7. ctDNA: The future of Adaptive Care, but not yet the standard.
ctDNA was another topic widely discussed at ESMO Breast 2026, particularly its role in detecting molecular residual disease and monitoring the risk of recurrence.
Potential benefits of ctDNA:
Please assess the risk of relapse.
Molecular residual disease was detected before it was visible on imaging.
Help design a clinical trial for escalation or de-escalation.
It could be used to track response or resistance in the future.
However, it is important to note that ctDNA should not yet be used as routine standard care to change treatment plans in patients with early breast cancer outside of clinical trials because there is insufficient evidence that changing treatment based on ctDNA positivity significantly improves outcomes.
It can be said that ctDNA is a very promising tool, but currently it should be used in the context of research, registries, or protocols with clear governance.
8. Quality of life, young patients, and survival.
In addition to medication efficacy, ESMO Breast 2026 also emphasized issues related to quality of life, especially for younger patients and long-term survivors.
Key issues that should be emphasized:
Fertility preservation
Long-term side effects of endocrine therapy — such as tamoxifen and aromatase inhibitors.
Premature menopause
Sexual health
Bone health
Cardiotoxicity
Psychosocial support
Digital tools for monitoring symptoms and supporting patients.
This direction reflects the fact that the goal of breast cancer treatment is not limited to "survival," but also includes returning to a good life, having a suitable quality of life, and reducing the burden of unnecessary treatments.
9. Practical conclusions for the care of breast cancer patients.
Based on all the information, the take-home messages can be summarized as follows:
HR+/HER2–: Endocrine therapy is entering a more precise era, using molecular profiles after CDK4/6 inhibitor.
HER2-positive: De-escalation may be possible in selective and responsive patients, but caution is required.
TNBC: Immunotherapy and ADCs are core treatments, with selection based on PD-L1, BRCA, and treatment history.
HER2-low / Ultralow: This group expands the possibilities for using HER2-targeted ADCs.
ADCs: Drug ranking requires consideration of both the target and the payload, not just HER2 or TROP2.
ctDNA: Has high potential, but should still be used in clinical trials or specific protocols.
All groups: The goal is to increase cure rates, use treatment only as necessary, and maintain the quality of life for patients.
Summary
ESMO Breast 2026 demonstrates that breast cancer treatment is clearly entering the era of Adaptive and Precision Breast Cancer Care. Future treatments will not be decided solely on subtype, but will rely on information from biomarkers, genomic alterations, treatment response, ctDNA, and the patient's lifestyle context.
The most important thing is that modern breast cancer treatment must focus on three goals simultaneously:
Provide treatment that offers the highest possible chance of recovery.
Reduce unnecessary treatments.
Maintain the best possible quality of life for patients.
Applying the key takeaways from ESMO Breast 2026 at Numarak Hospital.
As a specialized breast and breast cancer hospital, Numarak Hospital is committed to applying international knowledge and treatment standards to all patients.
Guidelines for applying ESMO 2026:
Precision endocrine oncology for HR+/HER2 – uses molecular profile + biomarker panel for treatment planning.
Multidisciplinary tumor board — A team of 5 breast surgeons + oncologists review cases together.
KEYNOTE-522 protocol for TNBC — Pembrolizumab + Chemotherapy neoadjuvant
BRCA testing — recommended on TNBC for everyone, including younger HR+ individuals.
ADCs and targeted therapy — selected based on biomarkers and medical history.
Specimen Radiography and Scout Radar Localization — Reduce re-excision rate and increase surgical accuracy.
Survivorship Care + Patient Journey Coordinator — Focusing on quality of life after treatment.
Consult a specialist at Numarak Hospital.
To request a second opinion on your breast cancer treatment plan or to discuss standard ESMO 2026 treatment guidelines, please contact:
Tel: 02-059-0245
LINE: @namarak (page.line.me/vfg3683z)
Frequently Asked Questions from ESMO Breast 2026
What is ESMO Breast?
ESMO Breast (European Society for Medical Oncology Breast Cancer Annual Meeting) is an international scientific conference for medical oncologists, held annually by the European Society for Medical Oncology to present the latest research and guide the direction of breast cancer treatment.
What does "Less Chemotherapy" mean?
This refers to the concept of reducing chemotherapy in appropriate patients, not eliminating chemotherapy altogether. It's about selecting patients who benefit most from chemotherapy and reducing side effects for those who don't need it.
What are ADCs (Antibody-Drug Conjugates)?
ADCs are drugs that combine an antibody specifically targeting cancer cells with a payload (a drug that destroys cells) attached to the antibody, allowing for precise delivery to cancer cells. Examples include Trastuzumab Deruxtecan (T-DXd) and Sacituzumab Govitecan (Trodelvy).
What is ctDNA?
ctDNA, or Circulating Tumor DNA, is the DNA of cancer cells that has entered the bloodstream. It can be detected through a blood sample (liquid biopsy) and is used to assess the risk of recurrence and monitor treatment outcomes. However, it is not currently a standard diagnostic tool and is not performed outside of clinical trials.
What does HER2-Low mean?
HER2-low refers to a group of patients with low levels of HER2 protein expression (IHC 1+ or 2+ FISH negative). Previously classified as HER2-negative, these patients are now found to benefit from certain HER2-targeted ADCs, such as Trastuzumab and Deruxtecan.
KEYNOTE-522: What are the standard treatment protocols for TNBC?
KEYNOTE-522 was a clinical trial that demonstrated that the use of pembrolizumab (immunotherapy) in combination with chemotherapy in the treatment of neoadjuvant TNBC stage II-III resulted in a better response than chemotherapy alone — it is the current standard of treatment for early-stage TNBC.
What biomarkers should patients ask their doctors about?
Breast cancer patients should ask their doctor about standard ER, PR, HER2, and Ki-67 tests, and in some cases, BRCA, PIK3CA, ESR1, and PD-L1 tests, depending on the type and stage of the disease. At Namarak, the medical team will consider the appropriate tests for each individual.
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About the editor.
Assoc. Prof. Yaowanuch Kongdan, M.D., Breast Surgeon + Surgical Oncologist · Founder and Director of Namarak Hospital · President of the Thai Breast Disease Society (TBS) · Co-developer of the Breast Surgery Board Certification Curriculum and Examination System of the Royal College of Surgeons of Thailand.
Note: This article summarizes key points from the ESMO Breast 2026 conference for the informational purposes of healthcare professionals and the general public. It is not personalized medical advice. Appropriate treatment guidelines depend on the nature and stage of the disease, biomarkers, and individual health condition. Please consult a specialist for appropriate diagnosis and treatment.
References
European Society for Medical Oncology (ESMO) Breast Cancer Annual Meeting 2026
PHERGain-2 Trial — Response-Adapted Strategy for HER2+ Early Breast Cancer
SATEEN Trial — Sacituzumab Govitecan + Trastuzumab post T-DXd
KEYNOTE-522—Pembrolizumab + Chemo for Early TNBC
NCCN Clinical Practice Guidelines — Breast Cancer 2026
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