Lori Chan checks the cancer stem cell population in the department of...

Lori Chan checks the cancer stem cell population in the department of pharmacological sciences at Stony Brook University Hospital on Wednesday. Credit: Randee Daddona

Medical scientists have discovered a gene underlying one of the most lethal forms of breast cancer, and at the same time are proposing a way to block its activity, paving the way to successful treatment for a type of cancer that is tough to treat.

Lori Chan and her team at Stony Brook University have been studying a form of breast cancer known as “triple negative,” a designation that means three key markers are missing on tumor cells. These markers are the targets of medications that are used to successfully treat other forms of the disease, boosting patients' survival. 

Chan and her team have identified a gene they have dubbed USP2, which is involved in driving the growth of cancer stem cells, an activity that aids in triple-negative breast cancer’s proliferation and spread. The scientists also figured out a way to block stem cells specific to the disease, making the cancer sensitive to treatment with conventional chemotherapy.

“This is one of the most lethal forms of breast cancer,” Chan said Wednesday. “These patients have tumor recurrences and metastatic disease, even though they are treated with chemotherapy.

“Triple-negative breast cancer tends to occur more often in younger women and is common in African-American women,” Chan said, noting that multiple studies also have shown that these two populations are vulnerable to this form of breast cancer. Such disparities, she added, are a major focus of Stony Brook cancer research.

The Triple Negative Breast Cancer Foundation, a patient advocacy organization in Norwood, New Jersey, has found that among African-American women who develop breast cancer, there is an estimated 20 percent to 40 percent chance of the disease being triple-negative. And while the cancer can affect anyone, according to the foundation, women of Hispanic descent also are inexplicably at elevated risk, as are women who possess a flawed BRCA 1 gene, which long has been associated with breast and ovarian cancers.

Triple negative means the absence of the protein HER2, as well as estrogen and progesterone markers on the surface of cancer cells. The cancer drug tamoxifen, for example, targets the estrogen marker, and the medication Herceptin zeros in on HER2. These therapies not only have made cancers associated with these markers treatable, but long ago helped boost survival rates, and for many, cured the disease.

Chan said it is time to do the same for patients with triple-negative breast cancer. She thinks targeting triple negative’s stem cells is a major step in that direction.

“There has been a huge need to find a therapeutic target to treat this kind of breast cancer, and we know now that the tissue making up this disease is enriched with cancer stem cells,” said Chan, whose data on triple-negative breast cancer is published in the scientific journal Cell Death and Disease.

Chan and her colleagues traced the molecular pathway that controls stem cell activity in triple-negative breast cancer, which helped them figure out how to block the gene’s activity. By blocking the gene, the team was able to eliminate proliferating stem cells, the key factor that made the cancer vulnerable to destruction by chemo.

The discovery arrives just five months after an advance that has promised to change how triple-negative breast cancer is treated. The discovery, however, has garnered mixed reviews because the treatment worked best in patients who had a specific genetic profile.

Medical scientists at 246 research sites found that patients with triple-negative breast cancer lived longer when treated with a combination of immunotherapy and chemotherapy compared with patients treated only with chemo. Immunotherapy is the burgeoning area of cancer treatment that can recruit the body’s immune system to fight cancer.

In the research reported in an October edition of the New England Journal of Medicine, the immunotherapy agent unmasked cancer cells that were hiding in the body, revealing them to the immune system for destruction. Triple-negative patients who received combination therapy lived 21.3 months, compared with 17.6 for those who were treated with chemotherapy alone. 

Patients who carried a specific gene, PD-L1, lived 25 months after treatment with combination therapy.

Current chemotherapies for triple-negative breast cancer, Chan said, kill the cancer but leave scores of stem cells behind to trigger recurrences.

Her new approach annihilates stem cells, dramatically siphoning away the source of triple-negative breast cancer's aggression. 

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