In an op-ed article titled “My Medical Choice” published earlier today in the New York Times, famedHollywoodactress Angelina Jolie writes that she, after learning that she carries a mutation of the BRCA1 gene which critically increases her risk of developing breast and ovarian cancer, made the decision to have a preventive or prophylactic double mastectomy.

In the op-ed article Jolie explains: “My doctors estimated that I had an 87% risk of breast cancer and a 50% risk of ovarian cancer, although the risk is different in the case of each woman. Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could. I made a decision to have a preventive double mastectomy.”

BRCA1 and BRCA2
The Breast Cancer Susceptibility Gene (BRCA1) and Breast Cancer Susceptibility Gene 2 (BRCA2) are two types of tumor-suppressing genes. In normal cells BRCA1 and BRCA2 help stabilize the cell’s DNA and prevent uncontrollable cell growth. However, mutations in BRCA genes can lead to breast or ovarian cancer.

While both genes are very similar, harmful mutations in BRCA1 can lead to breast cancers that are harder to treat because they do not respond to hormone therapies used to treat tumors that occur more often in women with BRCA2 mutations.

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Breast cancer risk
Breast cancer is the most common cancer in women worldwide, comprising 16% of all female cancers. Estimated from the World Health Organization show that 519 000 women died in 2004 due to breast cancer. And although breast cancer is thought to be a disease of the developed world, a majority (69%) of all breast cancer deaths occurred in developing countries (WHO Global Burden of Disease, 2004).

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Furthermore, current incidence rates compiled by the National Cancer Institute (NCI), show that 12.4% of women born in the United States today will develop breast cancer at some time during their lives. But for women with a harmful BRCA mutation, the risk of breast cancer quintuples to 60%.

Family history: a need for screening
TheU.S. Preventive Services Task Force(USPSTF) recommends that only women with a strong family history be evaluated for genetic testing for BRCA mutations. This group represents only about 2% of adult women in the United States. The task force furtherrecommends that women should be referred for genetic evaluation if they have2 first-degree relatives (mother, sisters, daughters) with breast cancer, one of whom was diagnosed when they were younger than 50,3 or more first- or second-degree relatives (includes grandmothers, aunts) diagnosed with breast cancer, both breast and ovarian cancer among first- and second-degree relatives, a first-degree relative diagnosed with cancer in both breasts,2 or more first- or second-degree relatives diagnosed with ovarian cancer or amale relative with breast cancer.

The task force further recommends that women of Eastern European Ashkenazi Jewish heritage should be referred for genetic evaluation if they have afirst-degree relative with breast or ovarian cancer or2 second-degree relatives on the same side of the family with breast or ovarian cancer.

In Jolie’s case, her mother, actress and producer Marcheline Bertrand, died in 2007 of ovarian cancer at the age of 56 after a decade long fight.

Testing “patented” genes
Myriad Genetics, which created a test to screen for such mutations and is now involved in a legal struggle over the patentability of human genes, claims that the risk of breast cancer can be as high as 87% for women with BRCA abnormalities.Since testing became available in 1996, almost 1 million women have been screened.

Testing for the BRCA1 and BRCA2 mutations involved a simple blood test. However, because the test needs to be performed in a specialized laboratory, testing can be expensive – up to $ 4,000 per test. Unfortunately, many American health insurance companies may not always want to cover the cost of these genetic tests. The immediate result is that the costs may be prohibitive for many women. Furthermore, after the test, insurance companies may not want to pay for an elective, preventive or prophylactic mastectomy while others refuse to cover the cost of breast reconstruction on the grounds that this is merely cosmetic or aesthetic procedure.

And genetic testing does not benefit everyone. According to the Centers for Disease Control and Prevention(CDC) in Atlanta, only women with increased risk from family history of breast and ovarian cancer are likely to benefit from genetic testing. Only 3% to 5% of women who develop breast cancer have a BRCA mutation, and about 10% to 15% of women with ovarian cancer have a BRCA mutation.

“Personal and family history are the major determinants for genetic testing,” said Jennifer Klemp, Ph.D, MPH, director, Breast Cancer Survivorship Centerand a cancer risk genetic counselor at The University of Kansas Cancer Center. “But, there are many factors to consider when assessing risk and determining who is a good candidate for testing and many more in deciding when to remove your breasts and ovaries.”

Preventive treatment
A preventive or prophylactic mastectomy is an operation that removes all or part of the breast before cancer is diagnosed. In documented cases, the procedure may greatly reduce the risk of breast cancer, in some cases by up to 97%.

While this type of surgery has been shown to be helpful in studies of large groups of women, there is no guarantee that this procedure benefits any one woman. Some women with BRCA mutations will develop breast cancer early in life, and have a very high risk of getting a second breast cancer. Prophylactic mastectomy before the cancer occurs might add many years to their lives. But while most women with BRCA mutations develop breast cancer, some do not. These women would not benefit from the surgery, but they would still have to deal with its after effects.

Second opinions are strongly recommended before any woman makes a decision to have prophylactic surgery. The American Cancer Society Board of Directors states that “only very strong clinical and/or pathologic indications warrant doing this type of preventive operation.” But after careful consideration, this procedure may indeed be the right choice for some women.

Jolie, 37 years, old writes in her op-ed Jolie that she recently finished three months of medical procedures at thePink Lotus Breast Center(120 S Spalding Dr #205, Beverly Hills, CA 90212) in California on April 27, 2013. The procedure included the mastectomies and breast reconstruction.

Jolie details that her experience involved a three-step process. The first step took place on February 2, when she had a procedure that increases the chance that the nipple can be saved. Two weeks later, this procedure followed by the actual prophylactic surgery where the breast tissue was removed and temporary fillers were put in place. Finally, this preventive surgery was followed nine weeks later when Jolie underwent a reconstruction of the breasts with an
implant. “There have been many advances in this procedure in the last few years,” she explained, “and the results can be beautiful.”

Ovarian cancer
Women with a BRCA mutation may also be at higher risk for developing ovarian cancer. According to the National Cancer Institute (NCI) about 1.4% of women will have the disease sometime in their lives. But this risk increases to 15% to 40% for women with a BRCA mutation.

BRCA abnormalities in men
Although only 1% of all breast cancers occur in men, having a BRCA mutation means an increased risk, particularly for men with BRCA2 mutations. Harmful BRCA mutations also raise a man’s chance of developing cancer of the pancreas, skin or prostate.

Increase in prophylactic mastectomies
Jolie is not the only women at risk making the decision to opt for preventative treatment. The number of women undergoing a mastectomy is growing. A studypresented at the 2007 Annual Meeting of the American Society of Clinical Oncology(ASCO) showed thatprophylactic mastectomy in the United States more than doubled in less that 6 years. In the study, researchersidentified 152,755 patients with stage I, II, or III breast cancer; 4,969 patients chose contralateral prophylactic mastectomy. The rate was 3.3% for all surgically treated patients; 7.7%, for patients undergoing mastectomy. The overall rate significantly increased from 1.8% in 1998 to 4.5% in 2003. The researchers also found that contralateral prophylactic mastectomy rate for patients undergoing mastectomy significantly increased from 4.2% in 1998 to 11.0% in 2003. Interestingly, these increased rates applied to all cancer stages and including young patient age, non-Hispanic white race, lobular histology, and patients with previous cancer diagnosis associated with significantly higher rates.

Since the 2007 study, the numbers are increasing. MD Anderson Cancer Centerin Houston, Texas, reports an 8% increase of patients seeking prophylactic surgery in 2010. According to recent data this percentage increased to 12.6% in 2011, and rose again to 14.1% in 2012. Other National Comprehensive Cancer Network (NCCN) Institutes including the New York’s Memorial Sloan-Kettering Cancer Center, noted similar increases.

The Claudia Gilmore Story
In her New York op-ed, Jolie writes how she wants to encourage every woman to seek information from medical experts who can help them make important decisions. “This is,” she writes, “especially [important] if you have a family history of breast or ovarian cancer.”

A very well documented case of making a decision and dealing with the aftermath of a preventive mastectomy is that of Claudia Gilmore.

Claudia was 23 years old when, on January 11, 2011, she had a preventative double mastectomy with breast reconstruction. Her story is documented in a unique video project in which Gilmore shares her personal account of her experiences, feelings and decisions leading up to her surgery and what happened during her recovery and reconstruction.

For more information:
– BRCA1 and BRCA2: Cancer Risk and Genetic Testing [Key Points]
– Tuttle TM, Habermann EB, Grund EH, Morris TJ, Virnig BA.Increasing Use of Contralateral Prophylactic Mastectomy for Breast Cancer Patients: A Trend Toward More Aggressive Surgical Treatment. JCO November 20, 2007 vol. 25 no. 33 5203-5209 [Abstract]
– Claudia Gilmore’s Story: [Previve][Prologue][Choosing Doctors][The Glow of The Heart][Natural Form][Pink Pals][Me and the Media][Countdown][Recovery]
– Offsetting the Hereditary Risk of Breast and Ovarian Cancer – Mariah Isabella McDermott, Onco’Zine, 22 December 2011. [Full Article]
– Genetic Testing for Elevated Risk of Breast Cancer [Video]

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