Breast Cancer Subtypes
Breast Cancers Are Not All the Same
While breast cancer is often thought of as a single disease, increasing evidence suggests that there are multiple subtypes of breast cancer that occur at different rates in different groups, respond to different kinds of treatment, are more or less aggressive, and have varied long-term survival rates. In addition, risk factors may vary for each different subtype of breast cancer.
Overview of Breast Cancer Subtypes: Ductal vs. Lobular, In Situ vs. Invasive
Basal (Triple Negative) Breast Cancer
HER-2 Over-expression Breast Cancer
Luminal A and B Breast Cancers
Interactions of Breast Cancer Subtypes and Risk Factors
Genomics and Breast Cancer Subtypes
Breast cancer is not a single disease, and diagnostic and prognostic descriptions of subtypes of breast cancer have become increasingly sophisticated over the past decades. There are three basic groupings:
1) site of the tumor’s origin (ductal or lobular cancer);
2) whether the tumor is in situ (contained within the walls of the ducts or lobes) or invasive (extending beyond the walls); and
3) the reproductive status (pre-menopausal or post-menopausal) of the woman in whom the cancer has been found.
Age at diagnosis is also recorded, and often age 50 is used as a proxy for post-menopausal status. If the tumor is invasive, the number and location of lymph nodes that might be affected is recorded, as is information about whether or not the cancer has metastasized beyond the mammary and lymph systems. These factors form the basis of the TNM (Tumor, Nodes, Metastasis) system of staging breast tumors.
Based on a number of biological markers (proteins found in cells that have been associated with mechanisms underlying breast cancer), a newer set of breast cancer classifications has been established: basal, HER-2 over-expression, luminal A, luminal B, and unclassified (Perou, 2000; Sorlie, 2003; Aizart et al., 2012). As new technologies allow for easier descriptions of genetic, epigenetic and environmental chemical exposure profiles of individual tumors, the number and specificity of tumor classifications will inevitably increase substantially.
The basal subtype is also called “triple negative” cancer, because the cells are negative for three common markers: estrogen receptors (ER), progestin receptors (PR), and human epidermal growth factor receptor-2 (HER-2). Although the basal subtype is only found in about 15 percent of breast cancer diagnoses, it has been shown to be aggressive, unresponsive to treatment and, ultimately, indicative of a poor prognosis (Perou, 2000; Rakka et al., 2008). Basal-type breast cancer is diagnosed more often in African American women than in European-American women in the United States (Amend, 2006).
As the name suggests, HER-2 over-expression tumors have extra copies of the HER-2 gene and over-produce the resulting growth-enhancing protein. These tumors tend to grow quickly but are responsive to targeted drug treatment with compounds like Herceptin.
Luminal A and B subtypes are both estrogen-receptor-positive (ER+) and low-grade, with luminal A tumors growing very slowly and luminal B tumors growing more quickly. Luminal A tumors have the best prognosis.
Different cancer subtypes may be associated with different traditional risk factors. For example, one recent study indicated that incidence of luminal B breast cancer may be increased in women who gain substantial weight after age 18 (Tamimi et al., 2012).
Menopausal status may also interact with other factors in altering risk for developing particular subtypes of breast cancer. For example, more than five years of Hormone Replacement Therapy (HRT) is associated with higher incidence of HER-2 overexpressing cancers in postmenopausal women. On the other hand, for premenopausal women, being significantly overweight or obese increased risk for more aggressive triple negative breast cancer, while decreasing the risk for luminal cancers (Turkoz et al., 2013).
In the past couple of years, as the field of genomics has expanded, there has been an increase in the number of reports that have examined variations in gene (DNA) sequences and their protein products that might be associated with subtypes of breast cancers. Performing this kind of screening in large numbers of tumors with different markers (see above) is made possible by the development of high-throughput assays that allow scientists to examine the structure or function of thousands of genes and their products in a single experiment (Sims, 2009). In the largest study to date, researchers analyzed almost 2,000 breast tumor samples and determined that 10 separate subtypes of breast cancer could be identified, based on clusters of genes that were either expressed or not, in particular patterns (Curtis et al., 2012).
Yet even with these complex new ways of viewing the many subtypes of breast cancer, we do not yet have the tools to understand how they are related to the many environmental factors that increase the risk for breast cancer. That is one of the greatest challenges of the research agenda for the near future.