What is TNBC? How is triple-negative breast cancer treated?
- ป้าหมอนุช
- 15 พ.ค.
- ยาว 8 นาที
TNBC stands for Triple Negative Breast Cancer – a type of breast cancer that lacks the estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression. It accounts for approximately 15-20% of all breast cancers, is aggressive, grows/divides rapidly, and has a high recurrence rate within the first three years. The primary treatment is chemotherapy combined with immunotherapy (Pembrolizumab/Keytruda according to the KEYNOTE-522 protocol) before surgery, followed by surgery, radiation therapy, and PARP inhibitors in patients with BRCA mutations. Namarak Hospital has a multidisciplinary team and comprehensive technology for the treatment of TNBC.
What is TNBC?
TNBC (Triple Negative Breast Cancer) refers to breast cancer where three key receptors used to classify breast cancer are not detected.
ER (Estrogen Receptor): Negative — Cancer cells do not respond to estrogen.
PR (Progesterone Receptor): Negative — Cancer cells do not respond to the hormone progesterone.
HER2 (Human Epidermal Growth Factor Receptor 2): Negative — Cells do not overexpress HER2 protein.
Because it lacks these receptors, TNBC does not respond to hormone therapy (Tamoxifen, Aromatase Inhibitor) and HER2-targeted drugs (Trastuzumab/Herceptin) — requiring specific treatments that differ from other types of breast cancer.
Important information about TNBC:
Approximately 15-20% of all breast cancers are affected.
Aggressive — Cells grow/divide faster than other types of breast cancer.
It is more commonly found in patients under 50 years of age (premenopausal).
It is most common in BRCA1 mutation carriers — up to 70-80% of people with BRCA1.
The recurrence rate is highest during the first 1-3 years after treatment.
If 5 years pass, the recurrence rate is lower than that of other types of breast cancer.
Who is at risk of becoming TNBC?
This group of patients is at higher risk of developing TNBC than other groups.
Women under 50 years of age — TNBC is found more frequently in premenopausal patients than in postmenopausal patients.
Individuals with BRCA1 or BRCA2 mutations — particularly BRCA1 — are at high risk for TNBC.
Individuals with a family history of breast or ovarian cancer in direct relatives.
Certain ethnic groups —African and Hispanic women—experience TNBC at higher rates than other groups.
Women who have had multiple pregnancies or given birth at a young age.
TNBC is compared to other types of breast cancer.
Breast cancer is classified into major molecular subtypes based on the biomarkers detected.
Luminal A (HR+/HER2-, Low Ki-67): Found in ~40-50% — Slow growth, good response to hormone therapy, best prognosis.
Luminal B (HR+/HER2-/+, High Ki-67): Found in ~20-30% — Grows faster than Luminal A, may require chemotherapy.
HER2-Enriched (HR-/HER2+): Found in ~10-15% — Trastuzumab/Herceptin + chemotherapy provides significantly better treatment outcomes.
Triple Negative (ER-/PR-/HER2-): Found in ~15-20% — Aggressive but responds well to chemotherapy and immunotherapy.
Diagnosing TNBC
Confirmation of TNBC requires biopsy and specific biomarker testing.
Core Needle Biopsy: A tissue sample taken with a needle to confirm cancer.
Immunohistochemistry (IHC): Check ER, PR, HER2 — TNBC is indicated by ER < 1%, PR < 1%, HER2 0 or 1+.
FISH (Fluorescence In Situ Hybridization): Confirmation of HER2 in IHC 2+ cases.
Ki-67 Index: Measures the rate of cell division — TNBC typically has a high Ki-67 (> 20%).
Genetic testing (BRCA1/BRCA2): Recommended for all TNBC patients, especially those under 60 years of age.
PD-L1 Testing: To consider immunotherapy.
Treatment of TNBC
Treatment for TNBC requires a multimodal approach that combines chemotherapy, immunotherapy, surgery, radiation therapy, and targeted therapy in suitable patients.
5.1 Neoadjuvant Chemotherapy + Pembrolizumab (KEYNOTE-522 Protocol)
For stage II-III TNBC with large tumors or enlarged lymph nodes, treatment begins with neoadjuvant therapy (pre-surgical treatment) to reduce tumor size, increase the chances of breast-conserving surgery, and assess the cancer cell response.
KEYNOTE-522 Trial (Schmid et al., NEJM 2020):
A randomized Phase III trial in 1,174 patients with TNBC stages II-III compared pembrolizumab + chemotherapy with chemotherapy alone as a neoadjuvant.
Pathologic Complete Response (pCR): Pembro + Chemotherapy 64.8% vs. Chemotherapy alone 51.2%
Event-Free Survival at 5 Years Old: Pembro + Chemo 81.3% vs Solo Chemo 72.3%
Reduces the risk of recurrence or death by 37%.
Standard Regimen (KEYNOTE-522):
Cycles 1-4: Pembrolizumab + Carboplatin + Paclitaxel (every 3 weeks)
Cycle 5-8: Pembrolizumab + Doxorubicin/Epirubicin + Cyclophosphamide (AC/EC)
Post-surgery: Adjuvant pembrolizumab for another 9 cycles (total treatment duration ~1 year).
5.2 Surgery — Lumpectomy or Mastectomy
After neoadjuvant therapy, patients undergo surgery to remove any remaining cancer cells — the choice depends on the tumor's response and breast size.
Lumpectomy — If the tumor shrinks to an appropriate level, breast-conserving surgery is a good option.
Mastectomy — if the tumor is still large or has a multifocal appearance.
TAD (Targeted Axillary Dissection) — For patients initially presenting with enlarged lymph nodes, use Scout Radar marking before chemotherapy.
Sentinel Lymph Node Biopsy — for clinically node-negative.
5.3 Radiation Therapy
After surgery, patients often receive radiation therapy, especially after lumpectomy, to reduce the risk of recurrence. At Namarak Hospital, IORT (Intrabeam) is available as an option for eligible patients.
5.4 PARP Inhibitor (for BRCA Mutation)
Patients with TNBC and BRCA1 or BRCA2 mutations can use PARP inhibitors (Olaparib or Talazoparib) as adjuvant therapy after surgery. The OlympiA trial showed that one year of olaparib reduced invasive disease-free survival at four years from 80.4% to 86.1% in patients with BRCA+ HER2- early breast cancer.
5.5 Metastatic TNBC — A New Alternative
For metastatic TNBC (Treatment of NNBC that has spread to other organs), new and improved treatment options are constantly being developed.
Sacituzumab govitecan (Trodelvy): Antibody-Drug Conjugate targeting Trop-2 — ASCENT Trial: Extended overall survival from 6.7 to 11.8 months in patients with metastatic TNBC who had previously received chemotherapy.
Pembrolizumab + Chemotherapy: For Metastatic TNBC with PD-L1 positive (CPS ≥ 10) — KEYNOTE-355 Trial
PARP inhibitors: Olaparib or Talazoparib in BRCA mutation carriers.
New Antibody-Drug Conjugates (ADCs): Datopotamab deruxtecan, Trastuzumab deruxtecan (for HER2-low TNBC)
Pathologic Complete Response (pCR) — A key predictor.
Pathologic Complete Response (pCR) , meaning no cancer cells remain in the tissue sample after neoadjuvant treatment, is a key predictor in TNBC.
Patients with TNBC who received pCR after neoadjuvant therapy had significantly better long-term survival than patients who did not receive pCR.
The Keynote-522 protocol increased the pCR rate from 51.2% to 64.8%.
Patients not taking pCR — Capecitabine adjuvant may help reduce the risk of recurrence (CREATE-X trial).
Monitoring and Recurrence Risk
TNBC has a recurrence pattern that differs from other types of breast cancer.
Highest recurrence rate: Years 1-3 after treatment — peak in years 2-3.
After 5 years: The recurrence rate of TNBC dropped below HR+ Breast Cancer.
Follow-up: Physical examination + mammogram every 6 months for the first 2-3 years, then every 12 months.
Other imaging techniques: Ultrasound, MRI, at the discretion of the physician.
Circulating Tumor DNA (ctDNA): A new technology that may help detect minimal residual disease in TNBC.
Why choose TNBC treatment at Namarak?
A complete multidisciplinary team — 5 breast surgeons + oncologists + radiation oncologists.
KEYNOTE-522 Protocol — Neoadjuvant Chemotherapy + Immunotherapy (Pembrolizumab) according to international standards.
Intraoperative Specimen Radiography — Improves the accuracy of excision of tumors that have shrunk after neoadjuvant therapy.
Scout Radar Localization + TAD — for marking the original nodule and lymph nodes before neoadjuvant.
BRCA Genetic Testing — Recommended in all TNBC cases to consider PARP Inhibitor + Prophylactic Surgery.
IORT (Intrabeam) — in eligible postoperative patients.
Patient Journey Coordinator — Providing care throughout the treatment journey.
The philosophy of "like visiting a friend's house" — High Tech, High Touch
Frequently Asked Questions (FAQ)
Is TNBC more dangerous than other types of breast cancer?
TNBC is more aggressive than other types of breast cancer on average — it grows/divides rapidly and has a high chance of recurrence in the first 3 years. However, TNBC responds very well to chemotherapy and immunotherapy — with the KEYNOTE-522 protocol, patients receiving Pathologic Complete Response (pCR) have significantly improved long-term survival, and after 5 years, the chance of TNBC recurrence is lower than with other types of breast cancer.
Can TNBC use hormone therapy?
No — because TNBC lacks estrogen (ER) and progesterone (PR) receptors, hormone medications such as tamoxifen and aromatase inhibitors are ineffective. The primary treatments for TNBC are chemotherapy, immunotherapy, and in patients with BRCA mutations, PARP inhibitors may be used.
What is the Keynote-522 Protocol?
KEYNOTE-522 was a Phase III Clinical Trial published in the New England Journal of Medicine (2020) comparing the treatment of Stage II-III TNBC with pembrolizumab (immunotherapy) + chemotherapy versus chemotherapy alone. The addition of pembrolizumab increased the pathologic complete response rate from 51.2% to 64.8% and improved event-free survival at 5 years. It is now the standard treatment for Stage II-III TNBC.
TNBC: Do all people need to be tested for BRCA?
BRCA1/BRCA2 testing is recommended for all TNBC patients, especially those under 60 years of age, as TNBC is closely related to BRCA mutations — approximately 10-20% of TNBC patients have a BRCA mutation. Test results can influence treatment options (PARP inhibitors), consideration of prophylactic surgery, and recommendations for screening of family members.
Can TNBC undergo breast-conserving surgery?
Yes — especially after neoadjuvant chemotherapy where the tumor shrinks — lumpectomy + radiation has a local control rate and survival similar to mastectomy in suitable TNBC patients. The medical team will assess tumor size after chemotherapy and plan surgery individually. At Namarak, we use Scout Radar marking before chemotherapy to allow for the identification of the original tumor location even if it has completely disappeared.
Can IORT be used with TNBC?
In limited cases, IORT is best suited for early-stage TNBC with small, single-focus, and node-negative tumors. For most TNBC cases presenting with locally advanced disease requiring neoadjuvant therapy, whole breast radiation remains the standard. Our medical team will assess suitability on an individual basis according to the TARGIT-A protocol.
Could TNBC make a comeback?
Yes — TNBC has the highest recurrence rate in the first 1-3 years after treatment (peaking in years 2-3). However, if 5 years pass, the recurrence rate will decrease to a level lower than other types of breast cancer. Therefore, close monitoring during the first 3 years is very important. At Namarak, we use mammograms and other imaging tests as deemed appropriate by the medical team.
TNBC asks, "Should young women have their eggs frozen?"
It is recommended to discuss fertility preservation before starting chemotherapy — especially for patients under 40 who still wish to have children. Chemotherapy for TNBC (such as cyclophosphamide) may affect the ovaries and cause early menopause. The medical team may refer you for discussion about egg freezing or ovarian suppression (GnRH agonist) during chemotherapy.
About Numarak Hospital
Numarak Hospital is a specialized breast and breast cancer hospital located on Phetchaburi Road, Bangkok. Operating under the philosophy of "Like visiting a friend's house" — High Tech, High Touch — it combines international-standard technology with compassionate care.
To discuss TNBC or request a second opinion, please contact:
Note: This information is for general knowledge purposes only and is not personalized medical advice. Appropriate treatment guidelines depend on the nature, stage, and individual circumstances of the disease. Please consult a specialist for proper diagnosis and treatment.
References
NCCN Clinical Practice Guidelines—Breast Cancer (Version 2.2025)
Schmid P, et al. KEYNOTE-522 — Pembrolizumab for Early Triple-Negative Breast Cancer. NEJM 2020;382:810-821
Tutt ANJ, et al. OlympiA Trial — Adjuvant Olaparib for BRCA-mutated Breast Cancer. NEJM 2021;384:2394-2405
Bardia A, et al. ASCENT Trial — Sacituzumab govitecan for Metastatic TNBC. NEJM 2021;384:1529-1541
Cortes J, et al. KEYNOTE-355 — Pembrolizumab + Chemotherapy for Metastatic TNBC. Lancet 2020
