Neil L. Spector, MD, co-director, Experimental Therapeutics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, explains the need for an ample interpretation of breast cancer heterogeneity.

A breast cancer biopsy may reveal several different mutations, depending on the location examined on the biopsy. Even moving a short distance down the sample may reveal a completely different mutation profile. This complexity can easily become overwhelming, since over 50 mutations may be present on a single biopsy. However, Spector suggests that despite the large amount of data there may only be 2 mutations that are driving the entire tumor.

As an example, Spector compares breast cancer heterogeneity to a beehive. There may be multiple worker bees but only one queen. If you target the workers the hive will continue, but if you remove the queen it will die. Tumors operate in a similar fashion.

The true heterogeneous nature of a tumor has only recently been revealed. Due to current sequencing technology, several mutations that weren't visible before can now be detected. However, this information needs to be carefully interpreted, since it is not all essential.

Spector adds that there is a large amount of bioinformatics, such as genomics, proteomics, and metabolomics, which demonstrate the underlying complexities of the tumor system. There is a need to synthesize this data into something that can be discussed with an individual.

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Dr. Neil Spector, from Duke Cancer Institute, Explains Breast Cancer Heterogeneity


Dr. Spector Discusses Breast Cancer Heterogeneity

Neil L. Spector, MD, co-director, Experimental Therapeutics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, discusses the need for cancer researchers to investigate the entire system and tumor microenvironment. 

Studying the genomics of a tumor must advance to include the abnormalities in the entire system. In some cases the microenvironment may be offering the fertile ground that a tumor needs to grow. As an example, Spector notes that a cancerous cell containing multiple mutations can be planted in a healthy microenvironment and the malignant cells will not grow. This places extreme importance on understanding how the entire system affects the tumor. 

An example of a systemic effect on the tumor is the immune system. Understanding the immune system’s effect on the tumor may answer many of the questions about how tumors grow and respond to chemotherapy and targeted therapies. 

Dr. Neil Spector, from Duke Cancer Institute, Emphasizes the Importance of Studying Tumor Microenvironments

Dr. Spector on the Importance of Tumor Microenvironments

Neil L. Spector, MD, co-director, Experimental Therapeutics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, explains that specialists have a tendency to over simplify cancer, which is a very systemic disease that varies depending on the location and tumor type.

The cancer cells unique gene mutations while the area around the tumor and metastatic extensions may carry very different molecular characteristics. Spector describes it as "the seed versus the soil," where the tumor is the seed and the soil is the surrounding microenvironment.

The molecular differences observed between the tumor and microenvironment may lead to treatment resistance. These differences are further echoed by those seen in the primary tumor and metastatic sites, which are each molecularly unique. The varying molecular profile witnessed systemically can greatly affect the treatment paradigm.

Each of these molecular variations makes cancer extremely complex. Determining the systemic differences using molecular analysis will help researchers develop therapies and combinations of therapies that can have a dramatic break-through effect on the treatment of cancer.

Dr. Neil Spector, from Duke Cancer Institute, Discusses the Systemic Nature of Cancer

Dr. Spector Discusses the Systemic Nature of Cancer

Neil L. Spector, MD, co-director, Experimental Therapeutics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, explains that the initial data received from genomic, mutation, and gene expression analyses have illuminated the hidden complexities of cancer.

Historically breast cancer has paved the way in the research of molecular subgroups. The subclassification of this disease continues to dive deeper and researchers are now looking at subtypes of the subtypes.

While research has advanced, the area of triple-negative breast cancer still requires a more thorough subanalysis in order to provide better care. For instance, if a cancer is androgen receptor-positive it is more likely to respond to anti-androgen therapies. This allows for the personalization of care by providing the therapy that is most likely to be effective, based on genetics.

Tools are currently available to find the subsets that will likely respond to any given targeted therapy. This approach will help researchers pinpoint the targets that may or may not have an established therapy.

Dr. Neil Spector, from the Duke Cancer Institute, Discusses the Complexities of Cancer

Neil L. Spector, MD

Articles

Dr. Spector Discusses Breast Cancer Heterogeneity

Dr. Spector on the Importance of Tumor Microenvironments

Dr. Spector Discusses the Systemic Nature of Cancer

Dr. Spector Discusses the Complexities of Cancer