A new test for breast cancer?

Melissa Beattie-Moss
February 25, 2008
Raghu Sinha

Raghu Sinha

"Almost anything you can detect in the blood, you can also see in saliva," declares Raghu Sinha, enthusiastically.

Sinha may have reason to be excited: The associate professor of biochemistry and molecular biology at Penn State's College of Medicine is the principal investigator for a study that has garnered a fair share of attention in recent months. The study's hypothesis? That proteins specifically associated with breast cancer will be identified in the saliva of women with cancer. If distinct biomarkers—biochemical changes that correlate with the risk or progression of a disease—are shown to be present in cancer's earliest stages, such knowledge could potentially give rise to a saliva-based test for breast cancer.

A new diagnostic weapon in the war on breast cancer would be "an enormous, enormous breakthrough," Pat Halpin-Murphy of the Pennsylvania Breast Cancer Coalition has said. (One in eight American women will get the disease in her lifetime, and Pennsylvania is ranked fifth in the nation for breast cancer deaths.)

Explains Sinha, catching breast cancer in its earliest stages is critically important to long-term survival. Mammography—an imaging procedure using low-dose ionizing radiation—is currently the best way to screen for breast tumors and cysts, and is routinely recommended for women over age 40. Some studies suggest that annual or biennial mammography reduces the risk of dying from breast cancer by 40 percent.

However, the diagnostic technique isn't without risks and limitations. There is an approximately 10 percent rate of false positives, while false negatives (missed cancers) occur in 10 to 20 percent of those tested. In addition, some critics have raised questions about the risk of cumulative radiation exposure initiating the cancer process in healthy breast tissue, particularly in pre-menopausal women.

"Clearly, if women could be safely screened for breast cancer more frequently, we could prevent more deaths," remarks Sinha, adding that, at present, "it isn't practical or advisable to promote mammography every three months."

The simpler, non-invasive screening test Sinha and his colleagues envision is the focus of their current study, funded until December of 2008 through Penn State's Clinical and Translational Research Feasibility Grant program.

Inspired by recent research at the University of Texas that suggests detectable protein changes are present in saliva during cancer's earliest stages, Sinha and his three co-investigators— surgeon, J. Stanley Smith, geneticist Maria Baker, and oncologist Gregory Harper— have recruited 27 participants in the still-open study.

Participants must fit the study's three main categories: women with benign, pre-malignant breast disease; women with malignant breast cancer with or without a family history of the disease; and women with breast cancer who tested positive for an inherited mutation in their tumor-suppressing genes such as Brca1 and Brca2. (A control group of healthy women with no known breast disease has been recruited through the General Clinical Research Center.)

Explains Sinha, saliva has many advantages over serum as a clinical research tool, including ease of collection, storing and shipping. For human subjects, the non-invasive collection technique is easier to endure than repeated blood draws. Sinha's study is examining two kinds of saliva: whole—meaning it is composed of fluid from the three main salivary glands within the mouth—and parotid, from the parotid gland alone.

To obtain whole saliva, says Sinha, participants "chew a flavorless gum and spit into a long glass pipette that flows into a tube on ice to preserve the proteins," he describes. Parotid saliva is collected by means of a small cup inserted over the parotid gland inside the mouth, with tubing connected to a suction bulb. Participants "chew a brightly colored Jolly Rancher candy," which stains all their saliva, except that produced by the enclosed parotid gland. "In this way, we can check to see if there is any color in the parotid saliva and monitor the purity of the sample," Sinha notes.

"We are hoping to come up with a panel of proteins and assign a score to each, to develop an algorithm that could be useful in diagnosing cancers," he says, adding that although breast cancer takes years to develop, such biomarkers may begin to appear in saliva before a tumor has even formed.

If a sensitive saliva test (one that reliably distinguishes between benign and malignant tumors) could be developed, non-invasive screenings could become much more frequent—even potentially done during routine dental visits. In addition, says Sinha, suspicious mammogram results could be double-checked quickly and easily, allowing experts to better determine a patient's next treatment option.

Says Sinha, "It's still in the discovery phase at this point." His hope is that results from this pilot study will prompt support from federal agencies—and that salivary diagnostics can eventually become part of a front-line defense against breast cancer, supplementing ultrasounds, mammograms and biopsies.

Raghu Sinha, Ph.D. is associate professor of biochemistry and molecular biology at the Penn State College of Medicine and can be reached at rus15@psu.edu.

Last Updated February 25, 2008