CANCER
May 9, 2018

A Triple-Negative Threat

Basal-like breast cancer usually affects younger women. It is highly aggressive and largely untreatable. That may be changing.

Unlike most forms of breast cancer, basal-like breast cancer usually affects younger women. It is highly aggressive and largely untreatable. Now researchers have some idea why it's so different from other breast cancers and are cautiously optimistic that they've found a new treatment for it — in an unusual place.

The hormones estrogen and progesterone and the protein HER2, singly or in combination, make most breast cancer tumors grow faster. There are several drugs that counteract this effect, slowing down or even halting tumor growth in many breast cancer patients. But basal-like breast cancer is not strongly affected by estrogen, progesterone or HER2 and is not helped by treatments that target these three substances. Doctors term this type of breast cancer triple-negative.

Zoledronic acid is already approved to treat a number of diseases in people and is on the World Health Organization's list of safe and effective drugs, so it has fewer regulatory hurdles to clear than most other experimental drugs.

Because of the aggressiveness of this kind of breast cancer and its lack of response to mainstream treatments, people with basal-like breast cancer have a poorer prognosis than for any other breast cancer subtype.

The findings of researchers in China offer some hope, however. Reviewing the records of over 5,000 breast cancer patients, they found that patients with basal-like breast cancer had dramatically elevated levels of an enzyme called UGT8. Patients with higher UGT8 levels also tended to have larger tumors and a shorter lifespan.

The enzyme seemed to be driving the progression of the disease, so it looked like a reasonable therapeutic target. Drawing on previous knowledge that certain drugs called bisphosphonates could drastically lower the enzyme's activity, researchers decided to see if zoledronic acid, a drug used to treat osteoporosis and high blood calcium, might help.

What they found is that zoledronic acid both inhibited the enzyme UGT8 and impaired the cancer cells' ability to invade their surroundings in mice, preventing tumor formation and spread to the lungs. Said study co-author, Chenfang Dong, a Professor at the Zhejiang University School of Medicine, Hangzhou, People's Republic of China, “Our study suggests that UGT8 contributes to the aggressiveness of basal-like breast cancer and that pharmacological inhibition of UGT8 by zoledronic acid offers a promising opportunity for the clinical treatment of this challenging disease.”

While more study is needed, zoledronic acid is already approved to treat a number of human diseases and is on the World Health Organization's list of safe and effective drugs, so it has fewer regulatory hurdles to clear than most experimental drugs before it might be used as a cancer treatment in people.

The study appears in the Journal of Experimental Medicine.

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