Study: Cellular diversity in tumors may predict survival for some types of breast cancer

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People diagnosed with breast cancer that is "high-grade" or aggressive

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Checked Special populations: People with high-grade breast cancer

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Some tumors are made up of many different types of cells, while others contain generally the same cell type. This study found that among people with high-grade breast cancer, those who have tumors made up of many different cell types have a lower10-year survival rate than people with tumors containing only a single type of cells. This research is an early step towards developing a new test that can help physicians identify cancers that need more aggressive treatment, but more research is needed before it is ready for clinical use. (4/26/16)


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Findings     Limitations               
Questions for your doctor Resources and references


This study is about:

Whether having many different types of cells (immune cells and connective tissue cells in addition to cancer cells, for example) within a breast cancer tumor affects a patient’s survival.

Why is this study important?

Doctors want to be able to identify patients whose tumors need more aggressive treatment. If the presence of many different types of cells in a breast cancer tumor is a reliable marker for poor survival, this could be the basis of a test that would help doctors identify these patients

Study findings: 

  1. Patients with high-grade breast cancer and tumors with many different types of cells had a 51% chance of surviving to 10 years.
  2. Patients with high-grade breast cancer tumors without multiple cell types had a 70% chance of surviving 10 years.

What does this mean for me?

This research might become the basis of a test that predicts how aggressively a patient with high-grade breast cancer needs to be treated, based on the presence of multiple types of cells within the tumor. However, this is early research, and more work needs to be done before healthcare providers can use it in the clinic.

Questions To Ask Your Health Care Provider

  • Is my cancer considered high-grade?
  • I have an aggressive cancer—what are my treatment options?
  • Are there any tests currently available that predict which breast cancer patients will benefit from chemotherapy?



Study background:

Cancers differ from patient to patient. Some cancers grow quickly, while others evolve slowly. Some are more responsive to certain treatments. Physicians and researchers want to be able to identify cancers that are most dangerous and require the most aggressive treatment. Looking at cancer cells in different ways can help to predict their behavior. Researchers believe that the path a cancer takes depends on the two important characteristics: the cancer cells themselves, and how they interact with connective tissue (stromal) cells, immune cells, and other cells that surround and feed cancer cells. In this study, researchers looked at how the types of cells in and around the tumor, which they call the cancer’s ecosystem, can predict a patient’s chance of surviving their cancer.

In February 2016, Rachael Natrajan and colleagues at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research in the United Kingdom and other institutions published a study in the journal PLOS Medicine exploring this topic. Their study looked at how having connective tissue cells and immune cells in addition to cancer cells within a tumor affected a patient’s survival.

Researchers of this study wanted to know:

If there is a connection between having different types of cells, including cancer cells, immune cells and connective tissue cells within a tumor, and 10-year survival of patients.

Population(s) looked at in the study:

This research study used 1,026 breast cancer tumors from women diagnosed between 1980 and 2005.  

The researchers developed a program called the ecosystem diversity index (EDI) to determine which tumors had many different types of cells and which were composed of the same types of cells. A high EDI score (highest EDI=5) indicates that the tumor is extremely diverse (has many different types of cells); a low EDI score (lowest EDI=1) indicates that the tumor is made up of the same type of cells.

Study findings: 

  1. Patients with high-grade breast cancer and a high EDI score (indicating tumors with multiple, different cell types) had a 51% chance of surviving to 10 years after diagnosis.
  2. Patients with high-grade breast cancer and a low EDI score (indicating tumors made up of generally the same cell type) had a 70% chance of surviving 10 years after diagnosis.
  3. A high EDI score did not predict survival for patients with low-grade breast cancer—having multiple cell types in the tumor did not decrease or increase the likelihood that a patient would survive their cancer.
  4. Patients who had high-grade tumors, a high EDI, and a TP53 mutation in the breast tumor DNA had an even lower (35%) chance of surviving to 10 years.


The researchers designed their program to look only at the three major cell types in breast tumors. These cell types could have been broken down into subtypes, which might have affected the results. Interestingly, researchers found that a high EDI score only affected survival for grade 3 breast cancer tumors. This could mean one of two things: as the research suggests, EDI scores can predict patient prognosis only among those with grade 3 tumors, or that tumor grading may slightly differ between pathologists, which may be a limitation of this study.

It is also important to note that this research used banked tumor samples that were matched to patients’ medical records. This is a critical first step in developing new tests, but more research in newly diagnosed breast cancer patients who have the benefit of current treatments must be done before this type of test can be developed for use in patients.


Combined with genetic tumor testing, this study’s EDI scoring system may provide a future prognostic test. Further research must be done to confirm this finding, refine the test, and validate the results in patients before it can be used in the clinical setting.  

While this test is in its early stages, prognostic tests, such as the Oncotype DX, which reliably identifies women with ER+ early-stage breast cancer who can be treated with hormone therapy alone, are already available; XRAYS reviewed recent research on this test last year.

Posted 4/26/16

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