Tests for Personalisation
Personalised treatment protocols are mandatory in today’s management of breast cancer.
These characteristics are also called Molecular and Biological Markers.
Except for the phrase of “Breast Cancer” no other aspect of cancer could be similar between two women receiving treatment. And this is because Cancer of the Breast is heterogenous, meaning it has different characteristics, and it is these aspects that influence disease progression and response to treatment.
Molecular and Biological Markers for Breast Cancer are critical for diagnosis, prognosis (the probability of cure / disease reappearance), treatment decisions, and monitoring disease progression or recurrence. These markers provide insights into the biological behaviour of the tumour, including its growth patterns, likelihood of spreading, and response to therapies. Experts at Hyderabad Breast Clinics mandatorily and critically evaluate every patient through various tests like ER, PR, Her2Neu and when appropriate order further evaluation so that correct and appropriate treatment is instituted.
Personalization of breast cancer treatment
Involves tailoring treatment to a patient’s individual characteristics for best outcomes with least side effects and minimal costs of treatment.
Key Molecular and Biological Markers
Estrogen Receptor (ER):
- Found in ~70-80% of breast cancers.
- Indicates that the cancer is likely to respond to hormonal therapies (e.g., tamoxifen, aromatase inhibitors).
Progesterone Receptor (PR):
- Typically co-expressed with ER.
- PR-positive tumors also respond well to hormonal therapies.
- Overexpressed or amplified in ~15-20% of breast cancers.
- Associated with aggressive tumor growth but responds well to targeted therapies like trastuzumab (Herceptin), pertuzumab, or lapatinib.
- Tested using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
- Lacks ER, PR, and HER2 expression.
- Represents ~10-15% of cases and is often more aggressive with fewer targeted therapy options.
- May benefit from chemotherapy, immunotherapy, or newer agents targeting specific pathways (e.g., PARP inhibitors for BRCA-mutated cases).
- Tumor suppressor genes involved in DNA repair.
- Mutations are associated with a higher risk of breast and ovarian cancer.
- Impacts treatment decisions, especially the use of PARP inhibitors.
- Found in ~40% of HR-positive, HER2-negative breast cancers.
- Predicts response to targeted therapies like alpelisib (a PI3K inhibitor).
- Common in triple-negative and HER2-positive cancers.
- Associated with more aggressive disease and poorer prognosis.
- Evaluate the expression of multiple genes to predict the risk of recurrence and guide treatment:
- Oncotype DX: Scores recurrence risk in early-stage ER-positive, HER2-negative cancers.
- MammaPrint: Identifies high- or low-risk recurrence groups.
- Prosigna (PAM50): Classifies tumors into molecular subtypes.
- Measures the rate of cell division in tumor cells.
- A high Ki-67 index indicates aggressive tumor behavior and may guide treatment decisions.
- Assessed in triple-negative breast cancer for immunotherapy eligibility (e.g., checkpoint inhibitors like atezolizumab or pembrolizumab).
- A high level of TILs in TNBC and HER2-positive cancers suggests a better prognosis and potential response to immunotherapy.
- Associated with angiogenesis and aggressive disease.
- Associated with angiogenesis and aggressive disease.
Breast Cancer Molecular Subtypes
Breast cancer is classified into molecular subtypes based on gene expression profiles:
Luminal A (ER+/PR+, HER2-, Low Ki-67):
- Slow-growing, best prognosis, responds well to hormonal therapy.
Luminal B (ER+/PR+, HER2+/-):
- More aggressive than Luminal A, may require chemotherapy and targeted HER2 therapy.
HER2-Enriched (ER-/PR-, HER2+):
- Aggressive, responds to HER2-targeted therapies.
Basal-like (Triple-Negative):
- Aggressive, limited targeted therapies, responds to chemotherapy and immunotherapy.
Emerging Biomarkers
- Androgen Receptor (AR): Being studied for targeted therapies in AR-positive breast cancer.
- Cyclin D1: Overexpression in some subtypes.
- MicroRNAs (miRNAs): Indicators of tumor progression or therapeutic response.
- CTCs and cfDNA: Circulating tumor cells and cell-free DNA as liquid biopsy tools for monitoring disease progression.
