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What is triple negative breast cancer?

Understanding triple negative breast cancer begins with knowing that breast cancer comes in four basic varieties that depend on the receptor status—a term used to identify the proteins inside and/or around the tumor cells that bind to something in the body to trigger a reaction from the cell.

Most breast cancer cells are hormone-fed; these known as estrogen receptor positive (ER+) and progesterone-receptor positive (PR+). Others thrive on the human epidermal growth factor receptor 2 (HER2+). And then there’s triple negative (TNBC), the grouchy type in the breast cancer bunch that’s especially rude and unruly.

Of all breast cancers diagnosed in the United States, about 15 to 20 percent are triple-negative. Yet triple negative breast cancer isn’t a single type of tumor; at this point, it’s the tumors considered “other”—the ones that don’t fit into the better-known categories. Better understanding triple negative breast cancers is a primary focal point for investigators at IU School of Medicine. They’re working to identify differentiators within triple negative cancers with hopes of curing at least one type.

Characteristics

Compared to other types of breast cancer, triple-negative is more aggressive, higher grade and often shaped a lot like the cells that line the milk ducts in the breast. Terms like basal tumor, basal breast cancer, basal-like disease and basal-like genetic pattern all refer to the shape of the cancer cells. On a scale of 1 to 3, triple-negative tumors are often grade 3, the most unlike normal breast tissue.

In part because targeted therapy is not yet available for triple-negative breast cancer to reduce recurrence, it tends to come back within the first five years of finishing treatment—moreso than breast cancers that are managed with hormone or HER2  blockers. The good news is that after five years, recurrence is about the same for all types of breast cancer.

People of all races can get triple negative breast cancer. But, for reasons still being explored, triple-negative breast cancer shows up more frequently in African-American and Hispanic women than in the white population.

Treatment

All types of breast cancer are treated with the standard protocol of surgery, chemotherapy and radiation—in varying order based on size of the tumor, progression of disease and other considerations of specific cases. For tumors with receptors (ER+, PR+ or Her2+), targeted therapies are taken for about five years after completing this regimen to reduce recurrence. Triple negative breast cancer typically responds well to chemotherapy, but targeted treatment for triple negative breast cancer is not yet available. In part, that’s why triple negative breast cancer is more likely than other types of breast cancer to come back in other parts of the body, known as metastatic recurrence.

In other words, the cancer is diagnosed not by what causes it, but rather by what does not cause it. Without knowing the root cause of the cancer, researchers cannot develop targeted treatments designed to attack its unique vulnerabilities.

Active Research

Researchers at IU School of Medicine are focused on triple-negative breast cancers and trying to learn more about how these types of cancers behave and what puts people at risk for them. A wave of scientific and technological advancements makes this the prime time to focus on this disease.

First, genomic medicine is enabling researchers to read each tumor’s genetic blueprint, providing clues about the specific mechanisms it depends on to grow and survive. By analyzing the DNA of triple negative tumors, IU School of Medicine researchers hope to finally uncover what helps them flourish and develop precision therapies to interfere.

In addition, physicians and scientists are learning how to train the human immune system to mount its own defense against cancer cells. While still in its infancy, immunotherapy has the potential to be the most promising new therapy in a generation. IU School of Medicine faculty researchers believe the combination of genomically guided therapies and immunotherapies will allow for some types of triple negative cancers to be cured.

Finally, IU School of Medicine is launching one of the most ambitious longitudinal studies of triple negative breast cancer. The school will create a biobank of triple negative tumor tissue that will be mined for clues; collect health and other information from patients; and monitor long-term progress after treatment.

Frequently Asked Questions

Answers to common questions about IU School of Medicine’s work in triple negative breast cancer research are available here.

Triple negative breast cancer tends to be more aggressive and spreads more rapidly than other types of breast cancer, and it disproportionately affects younger women. It also has a higher recurrence rate, and once it has returned, standard therapy is often ineffective. A real need exists to develop new therapies for triple negative breast cancer, and IU School of Medicine aims to fill that gap.

Triple negative breast cancer simply means that the cancer tests negative for the presence of all three known receptors: estrogen, progesterone and HER2. In other words, the cancer is diagnosed not by what causes it, but rather by what does not cause it. Without knowing the root cause of the cancer, researchers cannot develop targeted treatments designed to attack its unique vulnerabilities.

IU School of Medicine has invested heavily in facilities and talent, which has led to scientific and technological advancements that makes this a great time to tackle this disease. For example, genomic medicine enables researchers to read each tumor’s genetic blueprint and gather clues about the specific mechanisms it depends on to grow and survive. By analyzing the DNA of triple negative tumors, IU School of Medicine researchers hope to finally uncover what helps them flourish and develop precision therapies to interfere. In addition, physicians and scientists here are learning how to train the human immune system to mount its own defense against cancer cells. While still in its infancy, immunotherapy has the potential to be the most promising new therapy in a generation. IU School of Medicine faculty researchers believe the combination of genomically guided therapies and immunotherapies will allow for some types of triple negative cancers to be cured.

Resourced for Discovery

IU School of Medicine is uniquely resourced to advance meaningful research in triple negative breast cancer.

Precision Health Initiative

Along with the extraordinary generosity of the Vera Bradley Foundation, Indiana University and IU School of Medicine have made monumental investments in talent and infrastructure to build a premier Precision Health Initiative. All told, IU has committed $120 million to precision health as part of the Grand Challenges program.  This funding is helping to develop critical infrastructure such as state-of-the-art genomic sequencing capabilities and a Chemical and Structural Biology Center, which focus on drug discovery.

Brown Center for Immunotherapy

In addition, the Brown Center for Immunotherapy was established in 2016 with a gift from tech entrepreneur and IU School of Medicine alumnus Donald Brown. All of these resources are being leveraged to advance triple negative breast cancer research at IU School of Medicine.

Breast Tissue Bank

IU School of Medicine is also home to the world’s only biorepository – or bank – of healthy breast tissue. The tissue is donated by selfless women without cancer who voluntarily undergo a breast biopsy. IU researchers are comparing healthy tissue from the bank to samples from women with triple negative disease to identify differences that may contribute to the growth of the cancer.

Biobank of Triple Negative Tumor Tissue

Finally, IU School of Medicine is launching one of the most ambitious longitudinal studies of triple negative breast cancer. The school will create a biobank of triple negative tumor tissue that will be mined for clues; collect health and other information from patients; and monitor long-term progress after treatment.