Thanks to research, we know breast cancer is not one but many diseases. At the molecular level, research has proven that a cancerous tumor is also comprised of different types of cells. These variations have serious implications for patients. By better understanding this process, researchers may be able to develop more personalized treatment plans based on the molecular makeup of a person’s tumor.
This concept, known as tumor heterogeneity, plays a fundamental role in how breast cancer behaves. To better understand this idea, BCRF spoke with Dr. Kornelia Polyak at the 2018 AACR Annual Meeting. Dr. Polyak is a renowned investigator who led some of the initial studies on this phenomenon.
If you picture a bucket filled with different colored balls, you can start to understand the concept of tumor heterogeneity. Red balls may behave differently than the green balls and yellow balls may behave differently than blue ones.
If you translate this concept to a tumor, its cells have different properties. While some may respond to treatment, others may not. In some cases, not all the cells are equally able to spread to other tissues – a process called metastasis.
How does tumor heterogeneity occur?
It only takes a few bad tumor cells in a tumor to alter the local tissue environment so that other tumor cells can grow and spread. This is more likely to occur in tumors with a high degree of tumor heterogeneity, which is commonly seen in triple negative breast cancer.
Dr. Polyak explains that there a several changes that occur in the tumor on the way to becoming heterogeneous and potentially able to spread.
1. Genetic diversity. Each time a cell divides there is an opportunity for genetic changes to occur. Pieces of DNA can be duplicated, lost or mutated. Because tumor cells go through rapid cell divisions and often lose the ability to repair the DNA damage, these genetic changes accumulate until ultimately the tumor is comprised of cells with different genetic programs.
2. Functional reprograming. Normal cells are governed by signals from their environment so that they function appropriately for the tissue where they reside. For instance, a breast cell looks and acts differently from a brain cell or a liver cell. Cancer cells don’t function as normal tissue. By turning genes on or off, they can dramatically alter their features and behavior. This creates a tumor with a diverse collection of cells with different properties.
3. Adapting to change. Normal cells cannot survive dramatic changes to their environment and breast cells were not designed to function in the liver or brain. Cancer cells create their own environment; When they need a blood supply, they create blood vessels. The also learn to adapt to different environments by acquiring new properties. It only takes a few cells like this in a tumor for the rest of the tumor to grow and spread.
Tumor heterogeneity and metastasis
Dr. Polyak explained that when the primary cancer is heterogeneous, it is more likely to metastasize, and the metastasis is also likely to be heterogeneous. Her studies have shown that in patients with heterogeneous tumors, systemic changes occur (in tissue and blood, for instance) before metastasis, suggesting that cells from the primary tumor are altering the environment to tumor spreading.
Her group is working to identify targets to prevent this, by blocking inflammatory molecules or other tumor programs.