Staci Mishkin was tested for the BRCA breast cancer gene mutation eighteen years ago; at that time she was one of the first women in the US to do so. Mishkin entered into a clinical trial because four of her relatives-her two aunts, grandmother, and mother-died of breast cancer. Her test results were positive, so she had her breasts and ovaries removed to protect herself. Today she is 50 years old-the first woman in her family to live that long.

Now, 18 years later, testing for the BRCA 1 and BRCA 2 gene mutations that cause breast cancer are the subject of intense debate. These mutations cause about five percent of all breast cancer cases, 15 percent of all ovarian cancer cases, and between 20 and 25 percent of all hereditary cases of breast cancer.

The subject is controversial. It is no longer cost-prohibitive to test for the BRCA gene mutations; there is a $249 test kit available now that assesses the BRCA genes and 17 others that increase cancer risk. The issue has also received more attention in the wake of Angelina Jolie's announcement that she had not only had a preventive double mastectomy, but also had her ovaries removed.

Jolie has the BRCA 1 mutation and "an estimated 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer." And like Staci Mishkin, Jolie lost her aunt, grandmother, and mother to cancer.

Jolie wrote an Opinion Editorial in The New York Times this past March discussing her decisions and motivations.

"I did not do this solely because I carry a BRCA1 gene mutation, and I want other women to hear this. A positive BRCA does not mean a leap to surgery. I have spoken to many doctors, surgeons and naturopaths.. . .There is more than one way to deal with any health issue. The most important thing is to learn about the options and choose what is right for you personally."

All of this makes two questions central to the debate: Who exactly should be tested for BRCA 1 and 2 mutations and what can positive test results indicate?

Everyone has the BRCA 1 and BRCA 2 genes. They produce proteins that suppress tumors, ensure the stability of the cell's genetic material, and repair DNA that has been damaged. The problem comes when these genes are mutated, preventing them from doing their intended jobs.

Family history is central to both the decision to undergo BRCA testing in the first place and the decisions that must be made after a positive result. Dr. Nadine Tung of the Beth Israel Deaconess Medical Center (BIDMC) Breast Cancer Genetic Risk Evaluation Program explains:

"The purpose of genetic testing is to identify those women and men who are at markedly increased risk of breast, ovarian and other cancers so that steps to reduce or eliminate that risk can be taken," explains Dr. Tung. "This can be achieved through intensive screening, medication or preventive surgery."

The BRCA mutation test is simple: just a blood test. What comes afterward is complex, however, and patients need to be prepared. This is why patients undergo pre-test genetic counseling; it is intended to assist patients in comprehending the ramifications of the test, and the possible results.

"It's complicated if the results come back positive," says Dr. Tung. "The cancer risks associated with mutations in some genes other than BRCA 1 and BRCA 2 are not yet known. In addition, mutations in other genes may confer high risks of cancers, although the benefit of screening or preventive surgery is unknown. And sometimes, changes are found in a gene and it isn't clear if that 'variant' is benign or worrisome. This can be stressful for patients."

And what about patients who receive the relief of a negative result, but still have a serious history of cancer in their family? Should the negative result reassure them? There is no clear answer to that question.

These complexities are why experts like Dr. Tung are worried about the easily accessible and cheap test kits that are now available.

"I think it's critical that patients undergo pre-test counseling before taking any genetic tests," Tung says. "Genetic counselors are equipped to not only provide patients with medical facts, but also help them to understand the many other issues that can emerge when you decide to find out if you carry a BRCA or other mutation."

Because patients may feel anxious about cancer running in their families and feel guilty at the thought of passing the gene on to their own children, counselors are equipped to help allay these concerns and also to recognize when a social worker should join the conversation if needed.

"Genetic tests can help guide patients in critically important decisions," says Tung. "But pre-test counseling, whether face-to-face with a counselor, or by teleconference is key to preparing patients for these tests and helping them to understand a complex and difficult issue."

Dr. Asher Salmon, senior oncologist of the Hadassah Hospital in Jerusalem, has just added another wrinkle to this debate by publicly renouncing automatic, universal testing for BRCA mutations in women as they reach age 30. This follows the April endorsement of testing for all women over 30 by Dr. Marie-Claire King, a University of Washington genetics researcher.

Dr. Salmon argues that without the benefit of extensive expert family history analysis and genetic counseling, the results of BRCA testing do not provide enough information to allow women to make intelligent decisions about possible treatment.

"30 percent of women tested will have a gene alteration for which we don't know the significance, whether it is dangerous or benign, leaving women in a state of uncertainly as to whether they are at risk or not. By the same token, testing negative for BRCA mutation does not mean a woman is risk-free for breast cancer and can skip regular mammograms or breast exams. She also needs to continue to take care of herself and choose a healthy lifestyle."

The position of experts in Jerusalem is of special significance because Ashkenazi Jewish women have BRCA mutations 10 times more often than non-Ashkenazi women. Whereas one in 800 members of the general population have a BRCA 1 or BRCA 2 mutation, about one in 40 people with Ashkenazi Jewish ancestry have them, according to The Centers for Disease Control (CDC).

"Women with a family history of breast cancer should be tested-maybe as early as age 25-but the majority of women never have to be tested" Salmon says. "We shouldn't be practicing one-size-fits-all medicine, but rather medicine with appropriate protocols, guidelines and individualized treatment based on patients' personal histories."