Case Studies Show Need for Counseling With Genetic Testing

BALTIMORE—Physicians must help patients sort through the many diagnostic, predictive, and therapeutic alternatives raised by genetic testing, a trio of genetic specialists from Johns Hopkins said at a meeting on clinical cancer genetics and genetic testing.

Discussing two case studies, Deborah K. Armstrong, MD, Barbara Bernhardt, MS, CGC, and Florence Houn, MD, MPH, emphasized that patients may have a hard time absorbing the welter of information that flows from the testing process.

An Uninformed Patient

As an example, they cited the case of a 31-year-old woman of Russian (non-Jewish) ancestry who had consulted her gynecologist with complaints of menorrhagia and pelvic pain. Upon examination, she was found to have an enlarged uterus and was scheduled for a hysterectomy. Her gynecologist sent off a sample for BRCA1 gene testing. When it came back positive for the mutation, he sent her to Johns Hopkins for genetic counseling without giving her the test result or any background information.

The woman had no idea what the test result was, that it meant she had a 50% increased risk for breast cancer, or what it might imply for her two young children. Nor had she been told the effects of surgical menopause.

She went ahead with the scheduled hysterectomy and was placed on tamoxifen (Nolvadex) a month later. She developed serious signs of menopause, including hot flashes and mood swings.

“When she came to Hopkins,” Ms. Bernhardt said, “we spent a long time talking to her. In fact, we probably overloaded her just because she knew so little to start with. She should have gotten more information earlier.”

Nine months later, she said, the woman is doing well but now understands that she is at increased risk for developing breast cancer. Her mother and her aunt have now asked about genetic testing for themselves. The mother had developed ovarian cancer at age 40 but has survived for 18 years.

The patient’s three brothers, however, showed no interest in testing, despite their own increased risk for prostate and colon cancers. “Men generally aren’t interested until they have daughters,” Ms. Bernhardt commented.

A Take-Charge Patient

In another case, knowledge of BRCA mutation status and family history induced a more aggressive approach on the part of the patient. She was a 39-year-old woman of Ashkenazi Jewish ancestry with a serious family history of breast and other cancers.

The woman’s paternal grandfather died of breast cancer at age 43, and both her parents had developed the disease before age 50. Her father also was diagnosed with laryngeal cancer and prostate cancer in his late 60s. Furthermore, the patient’s sister died of adrenal cancer in her 30s.

Both parents were tested for BRCA1 and BRCA2 mutations. The mother was negative for the three “Jewish” mutations, but the father was positive for the BRCA2 6174delT mutation.

The daughter decided to take out a large life and disability insurance policy before submitting to the BRCA genetic tests. Her decision about the insurance was prompted by fears that once the fact or results of her genetic testing entered her medical record, she might face discrimination in obtaining insurance.

Her tests indeed turned out to be positive for the BRCA2 6174delT mutation. “The news hit the patient very hard,” Ms. Bernhardt said, “and she immediately decided on prophylactic mastectomy and reconstructive surgery.” Ovarian cancer screening continues, and she is considering a future oophorectomy.

For women considering prophylactic mastectomy, Dr. Houn said that the procedure removes all visible breast tissue, but residual germ cells remain. Follow-up must include clinical chest examinations, she said.