Breast cancer is a diverse group of diseases, each with unique biological characteristics. Molecular subtyping classifies tumors based on their specific genetic and protein features. This approach provides a precise understanding of an individual’s disease, guiding more effective and targeted treatment strategies for improved patient outcomes.
How Breast Cancer Subtypes Are Identified
Breast cancer molecular subtypes are identified by specific biological markers on or within cancer cells, primarily Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). ER and PR are hormone receptors that, when activated by estrogen and progesterone, can fuel cancer cell growth. HER2 is a protein promoting cell growth, and its overexpression can lead to aggressive tumor behavior. These markers are identified through laboratory tests, typically immunohistochemistry (IHC), performed on tumor tissue from a biopsy or surgery. The Ki-67 protein, a marker for cell proliferation, is also assessed; a high Ki-67 index indicates faster-growing cancer cells, and their combined status with ER, PR, and HER2 categorizes breast cancer into its distinct molecular subtypes.
The Four Main Breast Cancer Subtypes
Luminal A
Luminal A breast cancer is ER+ and/or PR+, HER2-, and has low Ki-67 expression (typically <20%). These tumors are low-grade and slow-growing. As the most common subtype, accounting for about 68% of all breast cancers, Luminal A has a favorable prognosis, with lower relapse and higher survival rates. The five-year survival rate is around 94.4% to 95%. These cancers respond well to hormone therapy, such as tamoxifen or aromatase inhibitors. Chemotherapy may be considered for higher-risk cases, but its benefit is often more limited than hormone therapy.
Luminal B
Luminal B breast cancers are ER+ and can be PR+ or PR-. They can be HER2-negative or HER2-positive, but are defined by high Ki-67 expression (often >20%), indicating faster growth than Luminal A. These tumors are intermediate to high grade and more aggressive than Luminal A, comprising about 15-20% of all breast cancers. Prognosis is less favorable than Luminal A, with a higher recurrence risk and slightly lower survival rates. The five-year survival rate is approximately 90.7%. Treatment involves hormone therapy, combined with chemotherapy due to their aggressive nature and higher proliferation. If HER2-positive, targeted HER2 therapies are also included.
HER2-Positive
HER2-positive breast cancer is defined by HER2 protein overexpression. This subtype can be hormone receptor-positive or negative. HER2-positive cancers are aggressive and fast-growing, with a higher likelihood of spreading and recurrence, accounting for about 10-20% of all breast cancers. Despite their aggressive nature, HER2-positive cancers respond well to HER2-targeted therapies. Targeted therapies like trastuzumab and pertuzumab have significantly improved prognosis. Treatment combines HER2-targeted therapies with chemotherapy, and sometimes radiation and surgery. The five-year survival rate is around 84.8% to 91.5%, with localized cases having a much higher survival rate.
Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer (TNBC) lacks estrogen receptors (ER-), progesterone receptors (PR-), and HER2 overexpression (HER2-). This means traditional hormone therapies and HER2-targeted drugs are ineffective. TNBC is an aggressive form of breast cancer, exhibiting rapid growth and an increased risk of early metastasis and recurrence. It accounts for 10-20% of all breast cancer cases.
Prognosis for TNBC is less favorable than other subtypes, with a higher recurrence risk and lower survival rates. The five-year relative survival rate for localized TNBC is around 91-92%, dropping to 65-67% for regional spread and 12-15% for distant metastasis. Treatment relies on chemotherapy, often given before surgery (neoadjuvant) or after to reduce recurrence risk. Immunotherapy drugs, such as checkpoint inhibitors, are emerging as treatment options, particularly for PD-L1 expressing tumors.
Emerging Concepts in Breast Cancer Subtyping
Breast cancer classification continues to evolve, reflecting the disease’s complexity and heterogeneity. Less common molecular subtypes, such as Claudin-low and molecular apocrine, have been identified, highlighting breast cancer’s diverse biological landscape. Claudin-low tumors, for instance, are characterized by low expression of tight junction proteins and often display features associated with cancer stem cells and epithelial-mesenchymal transition, frequently falling within the triple-negative category. Beyond distinct subtypes, tumor microenvironment heterogeneity acknowledges that even within a single tumor, cancer cells can vary and interact differently with their surroundings. This variability influences tumor response and spread. Ongoing research uses advanced techniques like single-cell sequencing to identify co-existing cell populations and explore how these variations impact disease progression and treatment sensitivity, leading to more precise and personalized strategies.