Gene Profiling of Breast Cancer Tumors

written by Science Writer Heather Schmidt and Editor in Chief Ernesto Cullari

 

 

Second to lung cancer, breast cancer is the deadliest form of cancer affecting women. More than 250,000 thousand women are diagnosed every year. It’s so common that one in eight women will develop breast cancer. While there have been many advancements and new insights in the pathology, origination and the treatment of breast cancer, chemotherapy and radiation are still widely used at some point during a patient’s treatment. Although effective, these interventions are known to wreak havoc on a patient’s overall health, leading to unbearable side effects and to permanent changes to the body.

To improve the quality of life and the efficacy of treatments for breast cancer patients, researchers are starting to look into the unique genetic profiles of both the patient and the tumor.

There are several different types of breast cancer:

ER (endocrine receptor, “hormone receptor”) positive breast cancer (usually involving either or both estrogen or progesterone), HER2 positive breast cancer (over production of the protein HER), triple positive (presence of estrogen, progesterone and HER2) and tripe negative (the absence of any hormone receptors and HER2 involvement). Triple negative breast cancer is very often associated with a mutation in the BRCA1 gene.

Not all breast cancers are treated the same.

Endocrine positive cancers are usually treated with some form of hormone therapy; depending on the stage of the disease. Almost always, chemotherapy and/or radiation is involved at some stage (either pre- or post-operatively) coupled with surgical resection and hormone therapy i.e. tamoxifen. Endocrine positive breast cancers indicate the presence of either estrogen or progesterone receptors within a cancer cell, defining hormonal involvement (estrogen and/or progesterone) in the manifestation and progression of the cancer. Hormone therapy is usually designed to cut the supply of the responsible hormone; slowing progression and/or preventing return of the cancer.

HER2 positive breast cancer is usually aggressive in nature, and has a high incidence of returning. Along with chemotherapy, Herceptin has been shown to reduce the chance of the cancer returning. However, long term use of Herceptin has been correlated with lung and heart damage, prompting further investigation on how long patients should be taking this drug. There are several other forms of treatment for HER2 positive breast cancer, most of which are different forms of chemotherapy.

Some forms of breast cancer are more aggressive than others.

For those diagnosed with triple negative breast cancer, there are no standard therapies used to prevent the return of the disease. More often than not, triple negative breast cancer is associated with a mutation in the BRCA1 gene. This form of breast cancer is often aggressive, appears early in life and has a high incidence of returning. Chemotherapy and/or radiation along with surgical resection is the current standard of treatment for triple negative breast cancer patients.

Gene profiling of tumors is a recent tool used by researchers to better understand cancer subtypes. A breast cancer tumor has different genes than the person afflicted. By analyzing how these genes within the cancer are likely to express themselves, clinicians can predict whether or not a cancer is likely to return and its likeliness to metastasize. Advancements in tumor gene profiling would help doctors and patients make more informed treatment decisions. For example, patients whose tumors have a genetic profile indicative of a high likelihood of metastasis would be a prime candidate for chemotherapy. Tumor profiling in patients with estrogen receptor-positive cancers is currently being utilized to make treatment decisions.

Monoclonal antibodies provide targeted, effective therapy in certain types of breast cancer however there are considerable risks including lymphoma and almost always, chemotherapy and/or radiation is used in conjunction. Despite the effectiveness of chemotherapy and radiation, the crippling effects on healthy tissue is impossible to ignore. The need for effective, targeted therapy with a low side effect profile is ongoing.

There are new drugs surfacing that attack the cancer cell from a metabolic standpoint; identifying specific catalysts in the metabolism of a cancer cell then introducing limiting factors – essentially starving the cancer cell and preventing further growth. The decades old theory, The Warburg Effect explains the unique metabolism of a cancer cell and how to theoretically disrupt that pathway, ultimately leading to cell death. More recently, scientists have revisited this model and have found that drugging a cancer cells metabolism is not only effective but carries very low side effect profiles.

An area of promising research is Tyrosine-kinase inhibitors. These drugs target enzymes that are critical for cancer cell metabolism, interfering with the pathway for cancer cell growth. There are two currently approved for use by the FDA. The first is Nerlynx, which is approved for the treatment of HER2-positive early breast cancer. The second is Tykerb, which is approved for use in HER2-positive metastatic breast cancer.

A breast cancer diagnosis can be a frightening thing to experience. Interventions that are less toxic, attacking only the cancer cell, that preserve cosmesis and that lessen the incidence of recurrence are desperately needed.

Works Cited

Milne RL, Kuchenbaecker KB, Simard J. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nature Genetics. October 2017. doi: 10.1038/ng.3785.

NIH. https://ghr.nlm.nih.gov/condition/breast-cancer#genes