Overview
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer defined by the absence of three specific receptors known to drive the majority of breast malignancies: oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
Accounting for approximately 10–15% of all diagnosed breast cancers, TNBC is distinct in its biology, clinical behaviour, and treatment paradigm. Because the cancer cells lack these receptors, hormonal therapies (such as tamoxifen or aromatase inhibitors) and HER2-targeted therapies (such as trastuzumab) are ineffective. Historically, this left chemotherapy as the sole systemic option; however, recent advances in immunotherapy, antibody-drug conjugates (ADCs), and PARP inhibitors have significantly expanded the therapeutic landscape.
Key Clinical Features at a Glance
| Feature | Details |
|---|---|
| Receptor Profile | ER-negative (<1%), PR-negative (<1%), HER2-negative (IHC 0 or 1+, or ISH-negative) |
| Histology | Mostly Invasive Ductal Carcinoma (No Special Type); high rates of metaplastic, medullary, apocrine variants |
| Grade | Predominantly Grade 3 (High Grade) |
| Proliferation Index (Ki-67) | Typically High (>20%, often >50%) |
| Molecular Subtype | Overlap with “Basal-like” intrinsic subtype (~70-80% concordance) |
| Peak Incidence | Younger age (<50 years), Black and Hispanic women, BRCA1 mutation carriers |
| Metastatic Pattern | Visceral (lung, liver, brain), distant nodes; lower incidence of bone-only mets vs. HR+ disease |
| Recurrence Pattern | Early peak (1–3 years post-diagnosis); lower late recurrence risk (>5–8 years) vs. HR+ disease |
Aetiology and Risk Factors
While the exact cause of TNBC remains under investigation, several epidemiological and genetic factors are strongly associated with its development.
1. Genetic Predisposition
- BRCA1 Mutations: The strongest known genetic link. Up to 70–80% of breast cancers in BRCA1 carriers are TNBC. BRCA2 carriers also have elevated risk, though more commonly HR+/HER2-.
- Other Germline Mutations: PALB2, BARD1, RAD51C/D, CHEK2, and TP53 (Li-Fraumeni syndrome) confer moderate-to-high risk.
2. Demographic Factors
- Age: Median age at diagnosis is typically 10–15 years younger than HR+ breast cancer (peak 40–50 years).
- Race/Ethnicity: Incidence is 2-fold higher in Black women compared to White women in Western countries. Hispanic women also show elevated rates. Socioeconomic factors and ancestry-related genetic variants (e.g., African ancestry) contribute to this disparity.
- Reproductive History: Early menarche, nulliparity, or late age at first full-term pregnancy are risk factors. Conversely, multiparity and breastfeeding appear protective against HR+ disease but may increase or not affect TNBC risk—a phenomenon known as the “parity paradox.”
3. Lifestyle and Metabolic Factors
- Obesity: Particularly premenopausal abdominal obesity and metabolic syndrome are linked to higher TNBC risk via inflammatory pathways (IL-6, TNF-α) and insulin/IGF-1 signalling.
- Physical Inactivity: Independent risk factor.
Pathology and Molecular Classification
Immunohistochemistry (IHC) Definition
The diagnosis of TNBC is one of exclusion. Strict adherence to current ASCO/CAP guidelines is mandatory:
| Marker | Negative Definition (ASCO/CAP 2020/2023 Updates) |
|---|---|
| ER | < 1% positive nuclear staining (Allred score 0–2) |
| PR | < 1% positive nuclear staining |
| HER2 | IHC 0 or 1+ OR IHC 2+ (equivocal) with negative ISH (HER2/CEP17 ratio < 2.0, average HER2 copy number < 4.0 signals/cell) |
Clinical Pearl:** Low ER positivity (1–10%) is no longer classified as TNBC but as “ER-low” disease, which may derive benefit from endocrine therapy. Accurate quantification is critical.
Molecular Subtypes (Lehmann Classification)
Beyond IHC, transcriptomic profiling reveals heterogeneity within TNBC, guiding clinical trial design:
- Basal-like 1 (BL1) & 2 (BL2): High expression of cell cycle/DNA damage response genes; high Ki-67; sensitive to platinum chemotherapy.
- Mesenchymal (M) / Mesenchymal Stem-like (MSL): Epithelial-mesenchymal transition (EMT) markers; growth factor pathways (EGFR, PDGFR); poorer prognosis.
- Immunomodulatory (IM): High immune cell signalling (CTLA4, PD-1, PD-L1); best candidates for immunotherapy.
- Luminal Androgen Receptor (LAR): Androgen receptor (AR) driven; lower proliferation; potential target for anti-androgen therapy.
How Does It Look? (Imaging & Pathology Appearance)
This section details the radiological and microscopic phenotype of TNBC, crucial for radiologists, pathologists, and clinicians interpreting staging workups.
Radiological Appearance (Mammography, Ultrasound, MRI)
TNBC often presents with “benign-mimicking” features on imaging, contributing to diagnostic delays. Unlike HR+ cancers (often spiculated masses with calcifications), TNBC frequently looks like a circumscribed mass.
| Modality | Typical TNBC Features | Differentiation from Benign Lesions |
|---|---|---|
| Mammography (MG) | • Oval, round, or lobulated mass with circumscribed or microlobulated margins (up to 30-40% of cases).<br>• Lack of associated calcifications (only ~10-20% show calcifications vs >50% in DCIS/HR+).<br>• Low density (may be isodense to breast tissue), potentially obscured in dense breasts. | Mimics fibroadenoma or cyst. A “probably benign” (BI-RADS 3) assessment is dangerous in patients >40y or with risk factors. Biopsy is usually warranted for new circumscribed masses. |
| Ultrasound (US) | • Hypoechoic mass (darker than fat).<br>• Angular or irregular margins (more specific than MG).<br>• Posterior acoustic enhancement (increased through-transmission) – Classic “pseudo-benign” sign.<br>• Taller-than-wide orientation (less common than HR+).<br>• Chaotic internal vascularity on Doppler. | Posterior enhancement mimics simple cyst or fibroadenoma. Key differentiator: TNBC shows internal vascularity and heterogeneous echotexture; cysts are anechoic/avascular. |
| Breast MRI | • Rapid, intense enhancement (Type 1 kinetic curve: rapid wash-in, rapid wash-out).<br>• Rim enhancement (peripheral enhancement with central necrosis) – highly specific for high-grade TNBC.<br>• Irregular, spiculated, or “clustered ring” morphology.<br>• High background parenchymal enhancement (BPE) common in younger patients. | Most sensitive modality for extent of disease (multifocality/multicentricity) and chest wall involvement. Essential for neoadjuvant response monitoring. |
Imaging Pitfall: Because TNBCs are often triple-negative and high-grade, they grow rapidly. A “negative” mammogram 6 months prior to a palpable lump is common (interval cancer**). Clinical correlation is paramount.
Gross Pathology (Macroscopic)
- Cut Surface: Typically soft, fleshy, grey-white to tan, homogeneous.
- Margins: Often pushing (expansile) borders rather than infiltrative/stellate (scirrhous) appearance typical of HR+ tumours.
- Necrosis/Haemorrhage: Central necrosis and haemorrhage are frequent in larger tumours (>3 cm), correlating with the “rim enhancement” on MRI.
- Cystic Degeneration: Large tumours may appear cystic/multiloculated.
Microscopic Pathology (Histology)
- Dominant Type: Invasive Ductal Carcinoma, No Special Type (NST) – >80%.
- High Grade Features (Grade 3 Nottingham):
- Tubule formation: <10% (Score 3).
- Nuclear Pleomorphism: Marked (Score 3) – large nuclei, prominent nucleoli, high N:C ratio.
- Mitotic Count: High (>20/10 HPF typically; Score 3).
- Special Histologic Variants (Prognostic Significance):
- Medullary Carcinoma: Syncytial growth, pushing margins, heavy lymphocytic infiltrate (“medullary pattern”). Better prognosis than standard NST.
- Metaplastic Carcinoma: Heterologous elements (squamous, spindle, chondroid, osseous). Chemoresistant, poor prognosis.
- Apocrine Carcinoma: Granular eosinophilic cytoplasm; often AR+.
- Adenoid Cystic / Secretory Carcinoma: Usually triple-negative but indolent; ETV6-NTRK3 fusion; excellent prognosis.
Tumour Microenvironment (TME)
- Tumour-Infiltrating Lymphocytes (TILs): TNBC has the highest TIL levels of all subtypes. Stromal TILs (sTILs) are a validated prognostic and predictive biomarker.
- High sTILs (>50-60%): Associated with higher pathologic complete response (pCR) rates to neoadjuvant chemo/immunotherapy and improved survival.
- Low sTILs (“Cold” tumours): Immune-excluded or immune-desert phenotypes; resistant to checkpoint inhibitors.
- PD-L1 Expression: Assessed via Combined Positive Score (CPS) on immune cells (SP142 or 22C3 assays). CPS ≥ 10 indicates eligibility for first-line pembrolizumab in metastatic disease.
Symptoms and Clinical Presentation
TNBC shares general breast cancer symptoms but is distinguished by a more rapid onset and higher frequency of symptomatic detection (vs. screen-detected).
Primary Breast Symptoms
| Symptom | Clinical Characteristic in TNBC | Frequency / Notes |
|---|---|---|
| Palpable Lump | Most common presentation (>80-90%).<br>• Rapid growth (noticeable change in weeks).<br>• Firm, hard, irregular, often fixed to skin or fascia late.<br>• Often large at diagnosis (median 2.5–3 cm vs 1.5–2 cm for HR+). | Often self-detected. Interval cancers common. |
| Breast Pain (Mastalgia) | More frequent than HR+ disease (up to 30-40%).<br>• Caused by rapid stretching of Cooper’s ligaments or chest wall invasion. | Absence of pain does not exclude malignancy. |
| Skin Changes | • Peau d’orange (lymphatic obstruction).<br>• Erythema, warmth, induration – mimics mastitis/abscess (Inflammatory Breast Cancer phenotype is enriched in TNBC).<br>• Skin tethering, nipple retraction. | Inflammatory Breast Cancer (IBC): Clinical diagnosis (rapid onset erythema/edema >1/3 breast, peau d’orange, +/- lump). TNBC represents ~30-40% of IBC. Requires urgent biopsy + MRI. |
| Nipple Changes | Retraction, deviation, or bloody/serous discharge (less common than lump). | Paget’s disease of nipple is rare in TNBC. |
| Axillary Mass | Palpable lymph nodes (firm, matted, fixed) at initial presentation. | Indicates N2/N3 disease; upstages to Stage III. |
Systemic / Metastatic Symptoms (At Diagnosis ~5-10% are Stage IV)
TNBC has a proclivity for visceral and CNS metastasis. Symptoms depend on organ involvement:
| Metastatic Site | Presenting Symptoms | Clinical Urgency |
|---|---|---|
| Lung / Pleura | Dyspnoea, dry cough, pleuritic chest pain, pleural effusion. | High: Rule out lymphangitis carcinomatosa. |
| Liver | RUQ pain, hepatomegaly, anorexia, weight loss, jaundice (late), elevated ALP/GGT. | High: Liver failure risk. |
| Brain / CNS | Headache (progressive, morning), seizures, focal deficits (weakness, aphasia), ataxia, cognitive changes.<br>• Incidence: 10-15% metastatic; up to 25-50% at autopsy. Higher risk with basal-like phenotype. | Emergent: MRI Brain with contrast mandated for any neuro symptoms. |
| Bone | Bone pain (back, ribs, femur), pathological fracture, hypercalcaemia. | Less common as sole site vs HR+; usually part of polymetastatic disease. |
| Distant Nodes | Supraclavicular (Virchow’s node), internal mammary, cervical nodes. | N3 disease (Stage IIIC/IV). |
Paraneoplastic Syndromes (Rare)
- Hypercalcaemia of malignancy (PTHrP secretion).
- Eaton-Lambert syndrome (neuromuscular junction).
- Acquired von Willebrand syndrome (adsorption to tumour).
Diagnostic Workup
1. Tissue Diagnosis (Core Needle Biopsy – CNB)
- Gold Standard: 14G or 16G core needle biopsy under imaging guidance (US preferred).
- Mandatory Panel: ER, PR, HER2 (IHC + reflex ISH if 2+), Ki-67, PD-L1 (CPS).
- Germline Testing: Indicated for ALL TNBC patients (regardless of age/family history) per NCCN/ESMO guidelines (BRCA1/2 + panel).
2. Staging Investigations
- Locoregional: Diagnostic bilateral mammogram + targeted US; Breast MRI (highly recommended for TNBC to assess multifocality, chest wall, contralateral breast).
- Systemic (Stage IIB or higher, or clinical Stage III/IV):
- CT Chest/Abdomen/Pelvis (or PET-CT).
- Bone Scan (or NaF-PET).
- Brain MRI (Strongly considered for Stage III, or if neuro symptoms; routine screening controversial but common in trials).
3. Biomarkers Guiding Therapy
| Biomarker | Test | Clinical Actionability |
|---|---|---|
| PD-L1 (CPS) | IHC (22C3 or SP142) | 1st line Metastatic: Pembrolizumab + Chemo if CPS ≥ 10. |
| gBRCA1/2 | Germline NGS | Metastatic: Olaparib / Talazoparib (PARPi). Adjuvant: Olaparib (OlympiA criteria). |
| TMB / MSI-H | NGS / PCR / IHC | Pembrolizumab (TMB-H ≥10 mut/Mb or MSI-H/dMMR) – agnostic approval. |
| TILs (sTILs) | H&E Morphology | Prognostic (High = better outcome); Predictive (High = better pCR to chemo/IO). |
| AR (Androgen Receptor) | IHC | Experimental: Anti-androgens (Enzalutamide, Bicalutamide) for LAR subtype. |
Staging (AJCC 8th Edition / TNM)
Staging integrates anatomic (TNM) and biologic factors (Grade, ER/PR/HER2). TNBC is staged purely anatomically + Grade (Grade 3 upstages some T1/N0).
| Stage | T | N | M | Typical Clinical Scenario |
|---|---|---|---|---|
| IA | T1 (≤2 cm) | N0 | M0 | Small node-negative. |
| IB | T0/T1 | N1mi (micromets) | M0 | Micromets in nodes. |
| IIA | T0/T1 | N1 (1-3 nodes) | M0 | Node positive, small primary. |
| T2 (2-5 cm) | N0 | M0 | Larger primary, node negative. | |
| IIB | T2 | N1 | M0 | |
| T3 (>5 cm) | N0 | M0 | Large primary, node negative. | |
| IIIA | T0-T2 | N2 (4-9 nodes) | M0 | Heavy nodal burden. |
| T3 | N1/N2 | M0 | ||
| IIIB | T4 (Chest wall/Skin) | N0-N2 | M0 | Inflammatory (T4d) or skin/chest wall invasion. |
| IIIC | Any T | N3 (≥10 nodes / SCV / IMN) | M0 | Advanced nodal disease. |
| IV | Any T | Any N | M1 | Distant metastases. |
Note:** TNBC does not receive the “prognostic stage” down-staging benefit that HR+/HER2- tumours receive. A Grade 3 T1N0 TNBC is Stage IB (Anatomic IA -> Prognostic IB).
Treatment Management
Treatment is stage-dependent and increasingly biomarker-driven. Multidisciplinary Team (MDT) discussion is mandatory.
1. Early Stage (I-III): Curative Intent
Neoadjuvant (Pre-operative) Systemic Therapy – Preferred Approach for Stage II-III
- Goal: Downstage tumour/axilla, assess response (pCR), tailor adjuvant therapy.
- Standard Regimens:
- Anthracycline/Taxane + Platinum (Carboplatin): e.g., Dose-dense AC → Paclitaxel + Carboplatin (GeparSixto, CALGB 40603). Platinum increases pCR rates (~55-65%).
- Anthracycline/Taxane + Pembrolizumab (KEYNOTE-522): Current Standard of Care for Stage II-III. Pembrolizumab added to chemo neoadjuvantly, continued adjuvantly.
- Result: pCR rate ~65% vs ~51% (placebo); Significant EFS benefit (HR 0.63).
- Response Assessment: Pathologic Complete Response (pCR = ypT0/Tis ypN0) is a validated surrogate for long-term survival in TNBC. Achieving pCR confers excellent prognosis (>90% 5-yr OS).
Surgery
- Breast: Lumpectomy (BCS) + Radiotherapy OR Mastectomy. Oncoplastic techniques for larger defects. pCR in breast allows less extensive surgery.
- Axilla: Sentinel Lymph Node Biopsy (SLNB) if cN0. Targeted Axillary Dissection (TAD) if cN1 converted to ycN0 (reduces false negative rate). Axillary Lymph Node Dissection (ALND) if residual nodal disease (ypN+).
Adjuvant (Post-operative) Therapy
- If pCR achieved (Neoadjuvant): Complete 1 year of Pembrolizumab (KEYNOTE-522). No further chemo. Radiotherapy per standard indications.
- If Residual Disease (No pCR):
- Capecitabine (CREATE-X): 6-8 cycles adjuvant. Standard for residual disease post neoadjuvant chemo (without IO). Improves DFS/OS.
- Pembrolizumab: Continue to complete 1 year (KEYNOTE-522 protocol).
- Olaparib (OlympiA): 1 year adjuvant for gBRCA1/2+ patients with high-risk early TNBC (Stage II-III or residual disease post-neoadjuvant). Significant DFS/OS benefit.
- Radiotherapy: Indicated post-BCS always. Post-mastectomy if pT3/T4 or pN+ (ypN+ counts). Regional nodal irradiation (RNI) for pN+.
2. Metastatic Stage (IV): Palliative / Life-Prolonging
Treatment sequencing depends on PD-L1 status, gBRCA status, prior therapies, and disease tempo.
First-Line (1L) Systemic Therapy
| Patient Subgroup | Preferred Regimen (Category 1 Evidence) | Key Trial |
|---|---|---|
| PD-L1 CPS ≥ 10 | Pembrolizumab + Chemotherapy (Paclitaxel, Nab-Paclitaxel, or Gemcitabine/Carboplatin) | KEYNOTE-355 |
| PD-L1 CPS < 10 (or ineligible for IO) | Chemotherapy Single Agent / Combination<br>• Taxane (Paclitaxel weekly / Nab-paclitaxel)<br>• Platinum (Carboplatin/Cisplatin) – esp. if BRCA+ or visceral crisis<br>• Anthracycline (if no prior adjuvant exposure)<br>• Eribulin / Capecitabine / Vinorelbine | Multiple |
| gBRCA1/2 Mutation | PARP Inhibitor (Olaparib / Talazoparib) Preferred over chemo if not visceral crisis / rapid progression needed. | OlympiAD / EMBRACA |
Subsequent Lines (2L+)
- Antibody-Drug Conjugates (ADCs) – Practice Changing:
- Sacituzumab Govitecan (Trop-2 ADC): Standard 2L+ (ASCENT trial). Superior to single-agent chemo (Eribulin, Capecitabine, Gemcitabine, Vinorelbine) for OS/PFS. Used regardless of Trop-2 expression.
- Trastuzumab Deruxtecan (HER2 ADC): Approved for HER2-low (IHC 1+/2+ISH-) and HER2-ultralow (IHC 0 membrane staining). TNBC patients must be retested for HER2-low status. (DESTINY-Breast04/06).
- Platinum Re-challenge: If long platinum-free interval (>6-12 months).
- Clinical Trials: Strongly encouraged at every line (novel ADCs, DDR inhibitors, IO combinations, CAR-T).
Special Considerations
- Brain Metastases: Local therapy (SRS/SRT/WBRT) + Systemic options with CNS penetration (Sacituzumab Govitecan, Capecitabine, Platinum, PARPi). Tucatinib + Trastuzumab + Capecitabine (if HER2-low).
- Bone Health: Denosumab/Zoledronic acid for bone mets.
Follow-Up and Survivorship
Surveillance Schedule (Early Stage, Post-Curative Treatment)
| Timeframe | History & Physical | Imaging | Labs / Other |
|---|---|---|---|
| Years 1-3 | Every 3–6 months | Annual Mammogram (+/- MRI if high risk/dense breasts). No routine CT/Bone/BM for asymptomatic. | CBC, LFTs if on adjuvant capecitabine/olaparib. |
| Years 4-5 | Every 6–12 months | Annual Mammogram | Assess late effects. |
| Year 5+ | Annually | Annual Mammogram | Transition to primary care/ survivorship clinic. |
Critical: No routine tumour markers (CA 15-3, CEA) or body scans for asymptomatic patients.** They do not improve survival and increase anxiety/harm.
Long-Term Toxicity Management
- Cardiotoxicity: Anthracycline surveillance (Echo/MUGA baseline, then symptom-driven).
- Peripheral Neuropathy: Taxane/Platinum induced. Duloxetine, PT/OT, fall prevention.
- Lymphoedema: Early referral to certified therapist (CDT).
- Fertility / Premature Menopause: Oncofertility referral pre-treatment. Non-hormonal management of vasomotor symptoms (SSRIs, Gabapentin, CBT, Fezolinetant).
- Bone Health: DEXA baseline + q1-2y if AI-induced menopause (rare in TNBC) or GnRH agonist use; Vit D/Calcium.
- Psychosocial: Fear of recurrence (FOR) high in TNBC due to aggressive biology/early peak recurrence. Screening (PHQ-9/GAD-7), survivorship care plans.
Prognosis and Outcomes
- Early Stage (I-III): 5-year Overall Survival ~85-90% (Stage I >95%, Stage III ~65-75%).
- pCR Achievement: 5-year OS >90-95%.
- Residual Disease: Higher risk, but Capecitabine + Olaparib (if gBRCAm) + Pembrolizumab have improved outcomes significantly.
- Metastatic (Stage IV): Median OS historically 12-18 months. Current median OS with sequential modern therapy (IO → ADC → PARPi → Chemo) approaching 24-30+ months. Long-term survivors (>5 years) emerging subset.
- Recurrence Pattern: “Front-loaded” – 50% of recurrences happen in first 3 years. Risk drops sharply after 5 years (unlike HR+ disease where risk persists 20+ years).
Prevention and Risk Reduction
| Strategy | Population | Efficacy / Notes |
|---|---|---|
| Bilateral Risk-Reducing Mastectomy (BRRM) | BRCA1/2 carriers, strong family history | Reduces breast cancer risk by >90-95%. Does not eliminate risk entirely. |
| Risk-Reducing Salpingo-Oophorectomy (RRSO) | BRCA1/2 carriers (age 35-40) | Reduces ovarian cancer risk >90%; Reduces breast cancer risk ~50% if premenopausal. |
| Chemoprevention | High risk (Gail model, LCIS, BRCA2) | Tamoxifen/Raloxifene: Effective for ER+ prevention; Limited/No proven efficacy for TNBC prevention. |
| Lifestyle | General population / Survivors | Weight management, physical activity (150 min/mod wk), limit alcohol, Mediterranean diet. Associated with lower recurrence risk. |
Frequently Asked Questions (FAQ)
Q: Is TNBC always fatal?
A: No. Early-stage TNBC is highly curable. With modern neoadjuvant immunotherapy/chemotherapy, pathologic complete response rates exceed 60%, translating to excellent long-term survival. Even metastatic TNBC survival is improving rapidly with ADCs and immunotherapy.
Q: Why is it called “Triple Negative”?
A: It defines what the tumour lacks (ER, PR, HER2). It is a definition by exclusion. It does not define what drives the cancer (which is heterogeneous), hence the search for new targets (Trop-2, PD-L1, PARP, AR).
Q: Does TNBC run in families?
A: It has a stronger hereditary component than other subtypes. ~15-20% of unselected TNBC patients carry a germline BRCA1/2 mutation. Testing is recommended for all TNBC patients regardless of age or family history.
Q: Can I have a baby after TNBC treatment?
A: Yes. Fertility preservation (oocyte/embryo cryopreservation) should be discussed before chemotherapy. Temporary ovarian suppression (GnRH agonists) during chemo reduces POI risk. Pregnancy after completion of therapy does not appear to increase recurrence risk (POSITIVE trial).
Q: What is “pCR” and why does my doctor talk about it so much?
A: Pathologic Complete Response (ypT0/Tis ypN0) means no invasive cancer found in breast and lymph nodes at surgery after neoadjuvant therapy. In TNBC, achieving pCR is the strongest predictor of cure. If pCR is not achieved, we have additional adjuvant treatments (Capecitabine, Olaparib, continued Pembrolizumab) to improve outcomes.
Q: Are there targeted therapies for TNBC besides chemo?
A: Yes. Pembrolizumab (Immunotherapy) for PD-L1+ (early and metastatic). Olaparib/Talazoparib (PARP inhibitors) for gBRCA mutations. Sacituzumab Govitecan (ADC) for metastatic 2L+. Trastuzumab Deruxtecan (ADC) for HER2-low/ultralow. Clinical trials offer access to newer agents (DDR inhibitors, novel ADCs, T-cell engagers).
Glossary of Terms
- ADC (Antibody-Drug Conjugate): A targeted therapy linking a monoclonal antibody to a cytotoxic payload.
- CPS (Combined Positive Score): PD-L1 scoring method: (PD-L1+ cells [tumour + immune] / Total tumour cells) x 100.
- DDR (DNA Damage Response): Cellular pathways repairing DNA; defective in BRCA-mutated cancers.
- EFS (Event-Free Survival): Time from randomization to recurrence, progression, or death.
- HR+/HER2-: Hormone Receptor Positive / HER2 Negative (Luminal subtype).
- IHC (Immunohistochemistry): Staining technique to detect protein expression in tissue.
- ISH (In Situ Hybridization): Genetic test (FISH/SISH/CISH) counting HER2 gene copies.
- NST (No Special Type): Standard invasive ductal carcinoma morphology.
- pCR (Pathologic Complete Response): Absence of invasive cancer in breast and nodes at surgery.
- TILs (Tumour-Infiltrating Lymphocytes): Immune cells within the tumour stroma; prognostic/predictive in TNBC.
- TNBC: Triple-Negative Breast Cancer.
References
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