Experts Support Jolie's Prophylactic Surgery Decision

Zosia Chustecka

March 27, 2015

Experts in gynecologic oncology have spoken in support of Angelina Jolie's decision to have her ovaries and fallopian tubes removed as a move against ovarian cancer.

Such surgery is the "cornerstone of management" in these cases, said Karen Lu, MD, professor of gynecologic oncology, codirector for clinical cancer genetics, and director of the High Risk Ovarian Cancer Screening Clinic at the University of Texas M.D. Anderson Cancer Center in Houston.

In an interview with Medscape Medical News, Dr Lu said that the star is representative of a growing number of women who are making decisions about cancer before they get cancer; they are described as "previvors" (in contrast to survivors who are living after cancer).

These previvors represent a new wave of patients that has never been seen before. These are women who have been genetically tested and found to have a very high risk for cancer, but have not yet been touched by cancer. "This is something new," she emphasized, "as previously we have been dealing with patients who first had cancer and then were tested and found to be at high risk."

Dr Lu also observed that these previvors have a different approach to the choices that are available to them than the average woman, or a woman with some family history of cancer, as they have very specific information about their risk as a result of the genetic testing. She also praised Jolie for speaking up on the issue of BRCA testing and the consequent medical choices available, and felt that it was beneficial for women who are in the same situation — "and there are growing numbers of these women," she noted.

Dr Karen Lu

As previously reported by Medscape Medical News, Jolie announced her latest surgery earlier this week in an op-ed in the New York Times. The star is a carrier of the BRCA1 gene mutation, which puts her at 87% risk for breast cancer and 50% risk for ovarian cancer. Two years ago, she underwent a bilateral prophylactic mastectomy, and now decided to undergo a prophylactic salpingo-oophorectomy at the age of 39. Her mother had died of ovarian cancer at age 49, her grandmother also died from ovarian cancer, and her aunt died from breast cancer.

"Based on what has been reported, including not only the genetic abnormalities, but also the family history of cancer, the decision by Ms Jolie was quite appropriate as a documented effective strategy to decrease the risk for the development of both breast and ovary cancer," Maurie Markman, MD, clinical professor at the Drexel University College of Medicine and senior vice president for clinical affairs at the Cancer Treatment Centers of America in Philadelphia, told Medscape Medical News.

Given Jolie's superstar status, the news of her latest surgery was widely reported in the media, and many outlets carried comments from medical experts supporting her decision to choose prophylactic surgery.

However, it was also pointed out that prophylactic surgery is an appropriate consideration only for women who are carriers of the BRCA gene mutations, particularly if they have a strong family history of breast or ovarian cancer. Only about 1% of women carry the BRCA gene mutations, although the incidence is higher among individuals of Ashkenazi Jewish descent.

Surgery Greatly Reduces Risk

Prophylactic salpingo-oophorectomy reduces the risk for ovarian cancer by about 85% to 90%, said Dr Lu. Even though both ovaries and fallopian tubes are removed, the risk is not eliminated entirely, because the same cells that develop into ovarian cancer are also found in the lining of the abdominal cavity, she explained. These cells can give rise to primary peritoneal cancer, which she described as a "cousin" of ovarian cancer.

So a small risk remains, but the risk is greatly reduced, Dr Lu said. Carriers of BRCA1 mutations have a greater than 50% risk of developing ovarian cancer; this surgery reduces that risk down to about 5%.

But isn't prophylactic surgery a rather drastic option, considering that it pushes a women into forced menopause, which has medical implications (menopausal symptoms of hot flushes, night sweats, but also increased risk for cardiovascular disease and osteoporosis)? In fact, the word "drastic" was used by several physicians commenting on our earlier report, and they wondered about alternative strategies.

Dr Lu emphasized that "removal of the ovaries and fallopian tubes is absolutely the cornerstone of management" for women who are genetically at very high risk for ovarian cancer, and she added that "screening has never been shown to be effective."

One point that she emphasizes to new patients who have tested positive for the BRCA mutations is that there is no rush for surgery. Many of these women are in their 20s when they test positive, she noted, and these decisions about prophylactic surgery don't need to be taken until they are in their mid- or late-30s, or even in their 40s, she said.

In the meantime, they can undergo screening, but even screening for ovarian cancer does not need to begin until mid-30s, she added.

Screening for ovarian cancer is carried out with the CA125 blood test and with ultrasound, both carried out at 6-month intervals. "We do it because these women are at such high risk," but she emphasized that there are no good data to support it and "it is important that these women are not falsely reassured."

An alternative to surgery, described as a "good" option for these women, is use of the oral contraceptive (OC) pill, which reduces the risk for ovarian cancer by 50%. "It cuts the risk in half," Dr Lu commented, so for a women who has a 50% risk for ovarian cancer, use of the Pill reduces the risk to 25%.

Asked about any potential for OCs increasing the risk for breast cancer, Dr Lu said there is a "myth that they do, but there are no data to show that."

There is another option, but this should be done only as part of a clinical trial, Dr Lu said. Her team is currently involved in such a study, and this involves two-stage surgery. At the first stage, only the fallopian tubes are removed, leaving the ovaries intact, which prevents the forced menopause. Then at a second stage, maybe a few years later, the ovaries are removed. The rationale for this two-stage process is that it gives the woman a few more years before enforced menopause, while removing the tissue in which the BRCA-associated ovarian cancer strikes most often. However, Dr Lu emphasized that this is an investigational approach at present, and should be carried out only within the confines of a clinical trial.

The forced menopause that follows this prophylactic surgery is usually treated with some form of hormone-replacement therapy (HRT), Dr Lu said. Although HRT is associated with an increase in the risk for breast cancer, the doses of hormones used are small, and so the overall hormone levels remain very low. "We do use HRT in women who have not had cancer," she said.

This is an important point, and one that has been usefully highlighted by the publicity about Jolie's decision, comments Andrew M. Kaunitz, MD, editor-in-chief on women's health at the New England Journal of Medicine Journal Watch.

"Many premenopausal BRCA mutation carriers defer risk-reducing gynecologic surgery because they dread the menopausal symptoms that inevitably follow loss of ovarian function. Understandably, such women — many of whom have seen their relatives battle breast cancer — worry that they cannot safely use hormone-replacement therapy (a concern shared by many clinicians)," Dr Kaunitz writes. "Contrary to conventional wisdom, however, evidence shows that BRCA mutation carriers with intact breasts can safely use hormone therapy for at least several years (J Natl Cancer Inst. 2008;100:1361-1367). In women who have undergone risk-reducing bilateral mastectomy, hormone therapy is associated with even fewer safety concerns."

Dr Kaunitz welcomes the publicity that Jolie has attracted about the issue. Two years ago, "her bravery in publicizing her decision to proceed with risk-reducing breast surgery encouraged many women with high-risk family histories to seek out genetic counseling and testing," he writes. "Now, [her] courage in sharing her story of risk-reducing gynecologic surgery should reassure mutation carriers that fear of severe menopausal symptoms need not deter them from making such lifesaving decisions," he adds.

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