Biomedical Frontiers: Fall 1996, Vol.4, No.1
The Cowden's-Breast Cancer Link

When Mary Smith (not her real name) was 16 years old, she found a lump in her breast. "My mother was terrified--she thought it was cancer," says Smith, now 53. "But in those days, no one talked about cancer. So even though I was scared that I had to have surgery, I didn't know the overwhelming possibilities." Since that surgery, Smith has had a seemingly endless series of cancer scares and actual bouts with cancer: four biopsies for suspicious breast lumps, a lumpectomy followed by a mastectomy, a hysterectomy, partial nephrectomy for what turned out to be a benign mass, and now, in 1996, another mastectomy.

CPMC researchers say that Cowden's syndrome-- a dermatological disorder--is an under-recognized cause of breast cancer.

Breast pathology is unique in Cowden's Syndrome.

Smith does not have the BRCA1 or BRCA2 breast cancer genes. Instead, she suffers from a little-known disease called Cowden's syndrome (CS; also known as multiple hamartoma syndrome)--an autosomal dominant disorder characterized by various skin lesions and a high risk of both breast and thyroid cancer. The medical literature describes CS as a rare disease associated with marked disfigurement. But according to CPMC's Dr. Monica Peacocke--who is collecting the genetic pedigrees of people like Mary Smith--CS is in fact fairly common, not generally disfiguring, easily missed by many doctors, and an under-recognized cause of many cases of familial breast cancer. "The genetic basis of many types of familial breast cancer is not yet known," says Dr. Peacocke, associate professor of medicine and of dermatology. "CS is masquerading as sporadic breast cancer."

Basically, CS patients "grow things," says Dr. Peacocke. Typically, those growths start as tiny wart-like bumps on the face, hands, feet, tongue, and lips. Women, among whom most cases occur, almost always develop severe benign fibrocystic breast disease, beginning in their teens. Because these benign tumors present as large, hard lumps of connective tissue, many doctors unfamiliar with CS immediately suspect cancer--a frightening experience at any age. By the time these women reach their 30s, an estimated 30 percent to 50 percent will develop breast cancer. "This is a breast cancer susceptibility syndrome with a cutaneous biomarker," says Dr. Peacocke, pointing out that innocuous looking skin growths may be associated with the expression of CS. These patients also seem to be at higher risk for skin cancer and suffer from thyroid abnormalities. Many suffer from hypothyroidism at an early age, benign tumors, and, occasionally, thyroid cancer. However, CS-related thyroid cancer is less common than breast cancer.

In the hope of learning more about CS, Dr. Peacocke is now conducting a search for the mutant CS gene using linkage analysis. This year a group of European researchers tentatively identified a suspect gene on chromosome 10. Dr. Peacocke is attempting to confirm these observations while focusing on other candidate genes. Since most CS patients are women, the syndrome may be linked to female hormones. In addition to her genetic research, Dr. Peacocke has become a national spokesperson of sorts for the disease. "In many ways, CS was an orphan disease when I started working on it two years ago and it still is today," she says. "Despite its association with breast cancer, the syndrome is virtually unknown to physicians outside dermatology."

A bumpy upper lip suggests CS.

Many women go from doctor to doctor for their symptoms, yet most of the doctors they typically consult--ranging from internists to endocrinologists to oncologists to surgeons--generally don't recognize CS, says Dr. Peacocke. "These women are always at the doctor, but until they get a cancer diagnosis, no one particularly pays attention to them," she says. Because early diagnosis would enable doctors to monitor CS patients closely for cancer, Dr. Peacocke has taken up the task of educating physicians. "I decided to become the 'voice' for CS. I have a cause," she says. For instance, although the medical literature describes the skin growths of CS as fairly obvious, many times they are actually subtle and can easily be missed by a physician without experience diagnosing CS. In addition, says Dr. Peacocke, many of the physicians likely to manage patients with CS--those who treat women who are at high risk for breast cancer or who have fibrocystic breast disease--are not familiar with CS. When Dr. Peacocke educated just one oncologist about CS, that doctor immediately identified five families in her practice with CS and breast cancer.

Treatment choices are also an issue with CS. Mary Smith, who knew she had CS, took tamoxifen after her second bout of breast cancer and went on to develop endometrial cancer that required a hysterectomy. "There is controversy over whether tamoxifen causes endometrial cancer," she says. "But probably someone like me shouldn't have been put on it."

Currently, there are no accurate counts of the number of people in this country who have CS, but most likely the syndrome is fairly common. "I see a new family [with CS] every week. And I talk to two to three new patients every day," says Dr. Peacocke. "CS presents in a large number of families with one to two cases." By gathering new clinical and genetic information on families with CS, Dr. Peacocke hopes to increase awareness and understanding of the disease.