Breast Cancer Classification

Breast cancers can be classified by different schema. They include stage (TNM), pathology, grade, receptor status, and the presence or absence of genes as determined by DNA testing :

1. Stage. The TNM classification for breast cancer is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) or spread to a more distant part of the body. Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis. The main stages are:
   
   • Stage Tis is Carcinoma In Situ (eg DCIS), a pre-malignant disease or marker.
   • Stages 1-3 are defined as 'early' cancer and potentially curable.
   • Stage 4 is defined as 'advanced' cancer and incurable.
   
   
2. Pathology. Most breast cancers are' derived from the epithelium lining the ducts or lobules. (Cancers from other tissues are considered "rare" cancers.) Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. Invasive carcinoma invades the surrounding tissue.[10] Cells that are dividing more quickly have a worse prognosis. One way to measure tumor cell growth is with the presence of protein Ki67, which indicates that the cell is in S phase, and also indicates susceptibility to certain treatments.
3. Grade (Bloom-Richardson grade). When cells become differentiated, they take different shapes and forms to function as part of an organ. Cancerous cells lose that differentiation. Cells that normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly-differentiated cancers have a worse prognosis.
4. Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. Cells with these receptors are called ER positive (ER+), ER negative (ER-), PR positive (PR+), PR negative (PR-), HER2 positive (HER2+), and HER2 negative (HER2-). Cells with none of these receptors are called basal-like or triple negative. ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to reduce estrogen (eg tamoxifen), and generally have a better prognosis.
   Generally, HER2+ had a worse prognosis, however HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly.
   All of these receptors are identified by immunohistochemistry.
   Receptor status is used to divide breast cancer into four molecular classes: (1) Basal-like, which are ER-, PR- and HER2- (triple negative, TN). Most BRCA1 breast cancers are basal-like TN. (2) Luminal A, which are ER+ and low grade (3) Luminal B, which are ER+ but often high grade (4) HER2+, which have amplified ERBB2.
   Finally, receptor status has become a critical assessment for all breast cancers, as it determines the suitability of using targeted treatments eg tamoxifen and or trastuzumab. These treatments are now some of the most effective adjuvant treatments of breast cancer. Conversely, triple negative cancer (ie no positive receptors) is now thought to indicate a poor prognosis.
5. DNA microarrays have compared normal cells to breast cancer cells and found differences in hundreds of genes, but the significance of most of those differences is unknown. Several screening tests are commercially marketed, but the evidence for their value is limited. The only test supported by Level II evidence is Oncotype DX, which is not approved by the U.S. Food and Drug Administration (FDA) but is endorsed by the American Society of Clinical Oncology. MammaPrint is approved by the FDA but is only supported by Level III evidence. Two other tests have Level III evidence: Theros and MapQuant Dx. No tests have been verified by Level I evidence (a prospective, randomized controlled trial in which patients who used the test had a better outcome than those who did not). In a review, Sotirou concluded, "The genetic tests add modest prognostic information for patients with HER2-positive and triple-negative tumors, but when measures of clinical risk are equivocal (e.g., intermediate expression of ER and intermediate histologic grade), these assays could guide clinical decisions."

Breast Cancer Treatment