Surgery reduces the risk of cancer

PHILADELPHIA — When genetic testing confirmed Brenda McCormick had inherited a BRCA1 mutation that virtually guaranteed ovarian cancer, she took her doctors' advice and had her ovaries and fallopian tubes removed.

Never mind that medical tests showed no signs of cancer, or that the surgery would plunge her into menopause at the age of 42. The disease had ravaged two of her sisters, killing one, and the Philadelphia area graphic artist knew the surgery was her best hope.

New research by 32 medical centers around the world confirms that this preventive surgery should be recommended to all women with BRCA1 or BRCA2 mutations, which cause 5 to 10 percent of all breast and ovarian cancers.

But the 3 1/2-year study of more than 1,800 mutation carriers — the first to follow such a large group — also clearly shows the pernicious, persistent effects of these inherited defects, even in women who take the drastic step of mutilating surgery. The disease is so hard to detect early that surgery often comes too late.

Of 490 women who opted to get rid of their ovaries and tubes during the research, 11 already had cancer.

So did McCormick, who was not in the study. Nineteen days after her genetic test results, surgeons at Fox Chase Cancer Center in Philadelphia found she had advanced ovarian cancer.

"The surgeon said it looked like a snowstorm in my abdomen," said McCormick, now 44. "If I had waited even a short period longer, it would have been inoperable."

Even successful risk-reducing surgery was no guarantee against cancer. Seven of the 555 women who sacrificed their ovaries and tubes before signing up for the study still developed cancer — of the peritoneum, the tissue that lines the abdomen. Four of them died.

While seven cases may not sound like many, it means that within 20 years of preventive surgery, a BRCA carrier still has a 4 percent chance of developing peritoneal cancer. The risk may be as high as 12 percent for carriers of BRCA1 mutations, said Steven A. Narod, a cancer geneticist at Toronto-Sunnybrook Regional Cancer Center and the study's senior author. By comparison, the average woman's chance of ovarian cancer is about 1 percent over her lifetime.

The study appears Wednesday in the Journal of the American Medical Association.

Researchers are only now starting to appreciate how often malignant changes spread to — or start in — the peritoneum. Narod estimates that 20 percent of ovarian cancers start in this lining, which can't be removed.