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Immunotherapy for Triple Negative Breast Cancer - A Potential Game Changer

Microscopic breast cancer tumor cell
Breast cancer tumor cell seen under a microscope

You may be hearing about a new type of treatment that is revolutionizing the way we fight cancer and could potentially be an option for those with triple negative breast cancer (TNBC). A type of immunotherapy called CAR T cell therapy, pioneered at Penn Medicine and recently FDA-approved, uses your own immune system to target aggressive and hard-to-treat cancer.

In the United States, about 15 to 20 percent of breast cancers are TNBC and often affect younger women and African Americans. It is an aggressive type of cancer that can be difficult to treat.

Julia Tchou, MD, Director of Breast Surgery Research and Section Chief of Breast Surgery at Penn, says that immunotherapy "would be a game-changer for triple negative breast cancer. Right now, there is no effective targeted therapy."

How Does Immunotherapy Work?

Immunotherapy works by using your own body to fight cancer. It boosts your body's cancer fighting ability by altering a part of the immune system called T cells. This technique is referred to as CAR T cell therapy, where your T cells are collected and manipulated to better target cancer cells.

Cancer cells are normally very good at tricking the immune system into leaving them alone, either by avoiding detection or switching off the immune system around them. By reprogramming T cells to be better cancer killers, Penn's CAR T cell therapy has shown remarkable success against young adult acute lymphoblastic leukemia (ALL), a blood cancer. To date, Penn has treated more than 400 cancer patients using CAR T cell therapy.

CAR T Cell Therapy for Triple Negative Breast Cancer

In TNBC, 'triple negative' refers to specific receptors on the breast cancer tumors. Breast cancer tumors are tested for estrogen, progesterone and HER2 receptors. If you test positive for any of these, there are treatments available to target those receptors

TNBC is 1) estrogen-receptor negative, 2) progesterone-receptor negative, and 3) HER2-negative, which means that it cannot be treated with hormone therapies or anti-HER2 targeted therapies. Hormone therapies such as tamoxifen can treat tumors that are progesterone-positive or estrogen-positive. Anti-HER2 targeted therapies can treat HER2 positive tumors.

Triple negative means there are few or none of these receptors. That leaves you with only a few good treatment options which consists of a combination of chemotherapy, surgery, and radiation therapy. But even this combination has sometimes failed to keep TNBC from coming back quickly and relentlessly.

Clinical Trials for Triple Negative Breast Cancer

To test the safety and efficacy of CAR T immunotherapy against TNBC, Dr. Tchou and her team are now enrolling patients in a Phase 1 clinical trial.

Julia Tchou, MD, PhD, FACS, Co-Director, Rena Rowan Breast Center In Dr. Tchou's trial, a patient's T cells are collected and altered to hunt down cancer with a specific marker called cMET on the surface of tumor cells. This cMET marker is common among women with triple negative breast cancer.

In their research, Dr. Tchou and Paul J.L. Zhang, MD, director of Penn's Immunohistochemistry Laboratory, found 60 percent of women with triple negative breast cancer have the cMET marker on the surface of their tumor cells.

Solid tumors like breast cancer have been a challenge for immunotherapy because they are better at evading the body's immune system.

A successful Phase 1 clinical trial would be the first step toward this treatment receiving FDA approval and becoming widely available.

MUC1 - The Common Denominator for Triple Negative Breast Cancer?

Researchers at Penn have found another promising target for CAR T immunotherapy. It's a cellular marker called MUC1. What makes this discovery so exciting is that MUC1, in particular, a sugar molecule on the surface of MUC1 appears to be common to all cancer cells, including TNBC. Normal cells do not have this "sugar-coated MUC1" which is also known as Tn-MUC1. That means patients with different cancers could potentially receive the same immunotherapy treatment that targets this tumor marker.

CAR T cell therapy targeting Tn-MUC1 is now being tested on mice that have been specially bred with human tumors. If that goes well, Penn will launch the first human trials targeting Tn-MUC1 by the end of 2018, Dr. Tchou says.

Dr. Tchou's lab is also looking at diabetes drug metformin and other well-established drugs with few side effects, like aspirin and statins, to see whether they lower the cancer risk. And her team is also studying how changes in lifestyle such as diet and weight loss effect the immune system, cancer prevention and cancer reoccurrence.

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The Focus on Cancer blog discusses a variety of cancer-related topics, including treatment advances, research efforts and clinical trials, nutrition, support groups, survivorship and patient stories.

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