ASCO Abstract # 1510
Patients with the phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), a rare genetic disorder that increases the risk of benign and malignant tumors, could be at a higher risk for colon cancer than once thought, say researchers at Mayo Clinic.
Their findings, to be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) held June 4–8 in Chicago, is one of the first outcomes from a unique pooling of clinical and genetic data from 46 PHTS patients — believed to be one of the larger collections from a single institution. The most common oncophenotype in this group is Cowden syndrome (80 percent).
The researchers are interested in PHTS because this inherited syndrome is caused by loss of the PTEN tumor suppressor gene, a frequently mutated oncogene involved in a variety of cancers. Researchers hope to link mutations in PTEN and associated molecular pathways seen in these patients to cancers that affect the general population.
“Patients with PHTS are almost encyclopedic in terms of malignancies,” says oncologist Mrinal Patnaik, M.B.B.S. “We believe the molecular pathway involved in the pathogenesis of PHTS is going to play a big role in multiple different tumor groups and that may help us identify new molecular targets and drug resistance pathways.”
But before the PHTS research team can delve into the genetic pathways involved in these cancers, they needed to define exactly which malignancies these patients develop.
Two studies to be presented at ASCO describe what they found. One concluded that patients with PHTS had a number of different cancers, including thyroid cancer (7 patients), breast (6), kidney (6), colon (2), endometrial (1), and ovarian (1). Additionally, six rare cancers were diagnosed in six patients.
Breast cancer in these patients was particularly aggressive, Dr. Patnaik says. Five of six patients had triple negative breast cancer and had developed metastatic disease within two years of diagnosis. Many patients had benign lesions on their thyroid (27), breast (11) and in other locations.
The second study examined results of colonoscopies that had been performed in 14 of the PHTS patients. Two patients were found to have cancerous polyps, seven had precancerous polyps, and the rest had a mixture of benign lesions and polyps that could become precancerous, Dr. Patnaik says.
“This tells us that this syndrome is associated with a spectrum of tumors in the colon,” he says. “This is rather unexpected. Most oncologists believe that these patients are not very susceptible to colon cancer, and the finding suggests PHTS patients may need to be regularly screened for colon cancer and watched for development of the other cancers we have documented.”
