By Dina Ingber Stein

At age 45, Karen Hanson* had her ovaries and fallopian tubes removed. She did not make this decision lightly. Karen’s family history and an inherited gene mutation put her at high risk of developing breast or ovarian cancer. My mother, my grandmother and all of my great aunts died of either ovarian or breast cancer,” says Karen. To deal with these risks, she was advised by a genetic counselor to undergo an oophorectomy–surgical removal of the ovaries–and a mastectomy, as well. “I decided not to get a mastectomy,” says Karen. She found out that oophorectomy can be performed as a same-day laparoscopic procedure and involves less physical scarring than breast surgery. In fact, recent studies have shown that the surgery would both improve her odds against ovarian cancer, and possibly significantly decrease her risk of developing breast cancer.

In 1994 and 1995, researchers discovered that mutations such as Karen's, on the BRCA1 and BRCA2 genes, posed greatly elevated risks of both ovarian and breast cancer. Two recent studies, published in The New England Journal of Medicine indicate that oophorectomy can significantly reduce breast cancer risk in women with these genes by as much as 50%. The studies were conducted at Memorial Sloan-Kettering Cancer Center in New York (www.mskcc.org) and at the University of Pennsylvania (www.cceb.med.upenn.edu/rebbeck/reb 2bc.htm). “We had long assumed that removing the ovaries could reduce the risk of ovarian cancer, but I doubt that many women realized an oophorectomy could reduce breast cancer risk as well,” says Timothy Rebbeck, PhD., Associate Professor of Epidemiology at the University of Pennsylvania School of Medicine and lead author on that study.

The experts are quick to point out, however, that this procedure is only for women with the BRCA gene mutation. “I would never advocate oophorectomy as a prophylactic measure against breast cancer for anyone who is not at very high risk for developing the disease,” says Dr. Rebbeck. The ovaries produce a range of hormones, including estrogen and progesterone, which have been linked to breast cancer. Removal of the ovaries eliminates those hormones, resulting in the onset of menopause. “An oophorectomy can have a serious impact on a woman's physical and emotional health, resulting in hot flashes, sexual dysfunction, an increased risk of heart disease and osteoporosis,” says Noah Kauff, M.D., Clinical Assistant Physician in Clinical Genetics and Gynecology Services at Memorial Sloan-Kettering and lead author of the second study. “Also, we don't fully understand the role played by each of the ovarian hormones and the long-term effect of eliminating those hormones.” In the first study, Dr. Rebbeck's team reviewed the medical histories of 241 women, ages 35 and up, with the BRCA gene mutation but no history of breast cancer. Over the course of eight years, 21 of the 99 women (21%) who had ovary surgery developed breast tumors, compared with 60 of the 142 women (43%) who did not undergo surgery. There was a more than 50% reduction in breast cancer in those who had their ovaries removed. Nearly 20% of those without the surgery received a diagnosis of ovarian cancer, while none of the women who had the surgery did, and only two developed a related form – peritoneal cancer. The Memorial Sloan-Kettering study identified 170 women over the age of 35 with the BRCA gene mutations who elected to undergo either a bilateral salpingo-oophorectomy (removal of both the ovaries and the fallopian tubes) or ongoing intensive screening and surveillance. Over a two year period, among the 72 women who chose surveillance, breast cancer was diagnosed in eight, ovarian cancer in four, and peritoneal cancer in one. Of the 98 who chose the surgery, breast cancer was diagnosed in three cases and peritoneal cancer in one. “Overall, oophorectomy reduced the combined risk for both breast and ovarian cancer by 75%,” says Dr. Kauff. “These studies indicate that this inherited predisposition can be greatly reduced, altering the natural history of the disease.”

The following statistics on risk factors may help you make your decision. According to Dr. Daniel Haber of the Center for Cancer Risk Analysis at Massachusetts General Hospital: • The prevalence of BRCA1 or BRCA2 mutations in the general population is 0.1 to 0.2 percent. • Approximately 10 percent of all cases of ovarian cancer are attributable to BRCA mutations. • Among women with breast cancer who have a very strong family history of breast and ovarian cancer – for example, more than three cases in three consecutive generations in either the maternal or paternal side of the family – the chance of having a BRCA gene mutation may be as high as 75%. • Carriers of a mutation in BRCA1 are thought to have a 50 to 85 percent lifetime risk of breast cancer and a 20 to 40 percent lifetime risk of ovarian cancer. Women with a mutation in BRCA2 appear to have a similar risk of breast cancer and a 10-to-20 percent risk of ovarian cancer. • Mastectomy appears to provide approximately 90 percent protection against breast cancer; oophorectomy is estimated to result in a 50% reduction in breast cancer risk.

The research, however, raises almost as many questions as it answers. For example, some women wonder how extensive the surgery has to be in order to provide the desired prophylactic effect. Experts agree that removing both ovaries is important in producing optimum protection. “When one ovary is removed, it is not clear whether the accompanying reduction in hormone exposure is enough to trigger a reduction in breast cancer risk,” explains Dr. Rebbeck. Removing the fallopian tubes along with the ovaries is also common practice. Another issue is the effect of Hormone Replacement Therapy (HRT), which replaces some of the very same cancer-linked hormones that the oophorectomy is meant to remove. “Our data so far suggests that HRT does not completely eliminate the benefits of the oophorectomy, but we don't yet know if it diminishes the effects of the surgery, or just how much HRT is safe,” says Dr. Rebbeck. Still another question which will be studied in a combined effort by both research teams is the difference, if any, between women with BRCA1 and BRCA2 gene mutations.

“In our experience, the lifetime risk of breast cancer for those with BRCA1 and BRCA2 are similar,” says Dr. Rebbeck. “But it seems that the cancer appears earlier in those with the BRCA1 gene. That may affect the timing for performing the oophorectomy.”

“Currently, because the average age for diagnosis is 40 for breast cancer and 50 for ovarian cancer, we feel that women can wait until after childbearing before undergoing the surgery.” Still, the decision to have an oophorectomy versus a mastectomy remains a very personal choice. “The hormonallymediated protection against breast cancer that follows oophorectomy is clearly more modest than the protection afforded by prophylactic mastectomy, but for many women, that may be a more acceptable procedure,” says Dr. Haber. “There are no numbers available as to how many women nationwide elect to have prophylactic oophorectomies, though in our own studies over 60% of women over 35 with the BRCA gene mutation elect to undergo the surgery,” says Dr. Kauff.

“It seems that most women are very satisfied with the decision, but for some, a mastectomy provides an increased psychological benefit. Many of these women live with the sense that breast cancer is just around the corner, and they want to do anything in their power to reduce their risk. I had watched my mother suffer and die, so there was no question in my mind about having surgery,” said Karen Hanson. “I went on the lowest dose of HRT immediately, and I have felt wonderful ever since.”

*Her name has been changed to protect her privacy. The model depicted in this story is not “Karen Hanson.”

Dina Ingber Stein is an award-winning freelancer who writes frequently on health-related issues for Family Circle, Glamour, Harper's Bazaar, Reader's Digest and Redbook.