Understanding Genetic Differences Between Breast Cancer Tumors Is Key to Better Treatment
Breast cancer is not a single disease. It is in fact, a collection of genetic changes that all lead to the same outcome: a tumor in the breast.
This means that breast cancer patients can’t be treated with identical therapies. Instead, therapy must be tailored to the underlying genetic changes that causes the tumor. To do this, physicians can look at a tumor’s genetic markers, which are called biomarkers. Looking at these biomarkers helps oncologists choose the treatment that is most likely to be effective in a particular tumor.
Based on her tumor’s biomarkers, a breast cancer patient could receive hormone therapy, targeted therapy or chemotherapy as her treatment course.
This is called “precision medicine,” and it has had some successes in breast cancer treatment. Many biomarker-based, or precision, therapies are now standard of care. But this field needs to be expanded further to improve overall patient outcomes.
Not only are tumors are different from one another, but there can even be genetic differences within a single tumor. These differences between tumors and within them are called tumor heterogeneity.
Our lab at Michigan State University, under the direction of Eran Andrechek, is studying how best to define the tumor heterogeneity and the effect that these differences have on a patient’s response to therapy. In particular, we are using next-generation technologies to understand tumor heterogeneity and define better treatment strategies for patients.
Tumor diversity makes treatment complex
To devise a better treatment strategy we have to understand how heterogeneity within and between tumors arise in the first place.
Tumors are a result of uncontrolled division of a single cell. However, a tumor is not the same throughout. Even though it starts with a single cell, the cells that make up the tumor are not all identical.
As a tumor cell divides, each daughter cell has mutations not present in the parent cell. This is called genetic instability. This multitude of mutations leads to a survival-of-the-fittest scenario within the tumor (this is called selective pressure).
Some of these mutations give cells an edge over other cells. Selective pressure means that cells with certain characteristics “win” the survival of fittest battle within the tumor. The result is that different “neighborhoods” of the tumor will be populated with clones of the fittest cells. Perhaps one region of the tumor is low in nutrients; it will contain cells that have picked up mutations to survive in a low nutrient environment. Another region might be under constant exposure to the body’s immune system; it will contain cells with immune evasion mutations. This is how differences within tumors emerge, and this diversity is also one reason why each patient’s tumor is unique, and subsequently why their tumor’s vulnerability to therapy is different, too.
This genomic instability also exists between patients.
A combination of random chance and differences in the genome lead to unique tumors to develop in each patient. Let’s say, for example, that we are looking at a group of breast cancer patients whose tumors all have the same biomarker.
Some patients have a complete response to a particular treatment tailored to that biomarker, meaning that the tumor shrinks and the patient is in remission.
The Conversation, a nonprofit source of explanatory journalism from experts in academia, is offering articles to The Associated Press for October Breast Cancer Awareness Month. Jonathan Rennhack and Jing-Ru Jhan are doctoral students at Michigan State University.