Breast cancer drug may play role in bladder cancer

Mayo Clinic researchers have found amplification of HER2, a known driver of some breast cancers, in micropapillary urothelial carcinoma (MPUC) and have shown that the presence of HER2 amplification is associated with particularly aggressive tumors.

These findings suggest that administering trastuzumab (Herceptin) to MPUC patients with HER2 amplification could improve outcomes, just as it has for breast cancer, according to the researchers, whose work appears online in Modern Pathology (Nov. 1, 2013).

As with breast cancer, HER2 amplification in MPUC results in a faster growing form of cancer that spreads quickly and has a higher chance of recurrence. The hope is that combating this amplification with trastuzumab, a drug that is effective in HER2 positive breast cancers, will result in effective therapy against bladder cancer.

“These findings show it is critical for pathologists to recognize this type of bladder cancer and that providers should be aware of and order the appropriate tests,” said lead author John Cheville, MD, of Mayo Clinic, Rochester, MN. “This will be essential for any clinical trial examining the effectiveness of trastuzmab in treating MPUC.”

The study identified HER2 amplification in 15% of patients with MPUC, compared to 9% of typical bladder cancers. Patients with HER2-amplified MPUC were more likely to have aggressive tumors than patients whose tumors did not have HER2 amplification, Dr. Cheville and colleagues found.

“In one sense, what we are trying to do with HER2-positive bladder cancer is a relatively simple thing. We are trying to identify prognostic and therapeutic biomarkers, and ultimately match the most effective drug to the individual patient’s tumor, rather than its location in the body,” Dr. Cheville said.

HER2 is a very important target in breast cancer therapy, and gene amplification occurs in approximately 20% to 30% of cases. Using the latest molecular techniques, Mayo Clinic researchers determined that some bladder cancers similarly show HER2 amplification and produce too much of the HER2 protein product, resulting in more rapid tumor growth and expansion.

In a related development, researchers at Loyola University Medical Center, Maywood, IL say a new study ultimately could lead to tests to screen for and diagnose bladder cancer.

The researchers studied microscopic exosomes, which are shed by cancer cells and are found in urine. Understanding the biology of exosomes could lead to the development of a screening test, which would require a simple urine sample, said lead author Gopal Gupta, MD, whose findings were published online in BioMed Research International(January 2014).

Dr. Gupta and colleagues used image cytometry to quantify how exosomes are taken up by cells. The study demonstrated how exosomes and their cargo can be transferred between cells. This supports the researchers’ hypothesis that shedding of exosomes from bladder tumors plays a key role in the cancer’s spread.

Characterizing how exosomes are taken up and internalized by bladder cancer cells “could become invaluable for understanding the role of exosomes on bladder cancer recurrence and progression,” the authors wrote.

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