Medical Mondays 2


Dr. Patricia Yarberry Allen likes to work as a collaborative physician. This week, she calls on the expertise of a gynecologic oncologist to address the anxieties  of  a 49-year-old woman with  “a terrible family history of cancer.”



Dear Dr. Pat:

I am 49 years old and have a terrible family history of cancer. My mother developed breast cancer while pregnant with my brother and died one year later. She was 36. Her father died of some kind of “stomach cancer” in his 50s, and her mother died at 70 of “natural causes.” She had only two brothers, and both are alive. One has had colon cancer and the other prostate cancer (at 62).  My father is 80 and healthy, and was an only child. His parents lived to an old age and did not die of cancer. I have one sister who had early breast cancer (DCIS…stage zero, I am told) when she was 45. She had a lumpectomy and radiation therapy and tamoxifen for five years. We both had BRCA testing five years ago, and we were told that we were negative. This year, at 52, she had a recurrence of breast cancer in the opposite breast that was Stage 1 ductal breast cancer. She had bilateral mastectomies with reconstruction and chemotherapy. The cancer was estrogen positive and HER2 Negative and she is now on Arimidex. My brother developed testicular cancer in his 20s. It was found early (we are compulsive about checking ourselves in this family) and he was treated and has no evidence of recurrence. I am the only one who has not been affected by cancer, but I expect it to strike every day. Clearly there is something genetic in my mother’s family, even if the BRCA testing was normal.  What should we do for screening?  Are there newer genetic tests?




Dr. Pat Responds:

Dear Valerie:

Primary care doctors who both teach their patients how to obtain an accurate family history and take a good family history hear stories like this all the time. Occasionally, I have patients who give vague answers to the important family history questions, and I send them home with a prescription for creating a genetic disease map of the family.  Accurate information does guide both physicians and patients as suggestions are made for appropriate testing; accurate information often provides facts that allow for reassurance, not anxiety.

In your case, however, there is certainly an increased risk for cancer. We know that the BRCA tests are useful only when positive, when there is a family history like yours. I tell patients that at this time, increased surveillance is our only option, but I give them hope that the genetic mapping of diseases is increasing at a rapid rate. That means that we will very likely find more genetic markers for familial cancers in the near future.

I have asked Dr. Elizabeth Poynor, a gynecologic oncologist who has a Ph.D. in cancer genetics, to discuss your question.


Dr .Pat


Dr. Elizabeth Poynor Responds:

Dear Valerie:

The BRCA1 gene was isolated and cloned in 1996, and soon thereafter the BRCA2 gene was cloned. The cloning of these two genes and the subsequent testing that could be offered to women put into motion our modern-day, widespread use of genetic testing for cancer risk analysis. BRCA1 and BRCA2 genes are called tumor suppressor genes. Mutations in these genes can increase the probability of developing certain types of cancers, most commonly breast and ovarian cancer. While testing for these genes has been used to guide clinicians and the women that they care for for nearly 17 years, this type of testing is in constant evolution as new discoveries are made—discoveries that further refine risk and management.  An ongoing dialogue for updates should be conducted between women who have a family history of cancer and the physicians who care for them. Today, the BRCA1 and the BRCA2 genes are the most common cancer genetic tests that are performed. If a woman has a mutation in one of these genes, she has an 80% to 90% chance of developing breast cancer and a 15 to 44% chance of developing ovarian cancer. Currently a single company, Myriad Genetics, performs the vast majority of BRCA1 and BRCA2 clinical testing.

It is important for women to understand that the BRCA test today is not the same one that was performed early on. Initially, only the “sequence” of nucleic acids in the DNA was analyzed and single site changes were detected.  Due to the way that sequencing is performed, larger deletions and rearrangements of nucleic acids cannot be detected. It then became apparent that these types of genetic alterations were involving the BRCA1 and BRCA2 genes and were leading to breast and ovarian cancer. In August of 2002, five-site large rearrangement testing was subsequently offered by Myriad, which detects 5 of the most common large rearrangements of the BRCA1 gene in European populations.  In August of 2006, the BRCA large rearrangement test (BART) was offered in order to detect additional large rearrangements in both BRCA1 and BRCA2.

Only about 50% of families that have a hereditary pattern of breast cancer (breast cancer in each generation) will test positive for a BRCA1 or BRCA2 mutation. Other cancer predisposition gene mutations, which have not been fully characterized, account for these hereditary cancers not associated with a BRCA1 or BRCA2 mutation. About 85% of families with a hereditary pattern of breast and ovarian cancer will be accounted for by an identifiable mutation in BRCA1 or BRCA2. Cancer predisposition genetic testing is now available for a number of other cancers, such as colon cancer, pancreatic cancer, and melanoma. Genetic “panels” are also being developed and are currently available through Ambry Genetics. These panels may be useful for families in which a BRCA1 or BRCA2 mutation has not been identified.

For women who are at elevated risk to develop breast cancer, either based on genetic testing results or family history, the following should be discussed: chemoprevention with agents such as Tamoxifen, Evista, and aromatase inhibitors; increased surveillance with mammograms and breast MRI; and prophylactic mastectomy. For women who are at increased risk to develop ovarian cancer, the following should be discussed: chemoprevention with oral contraceptives; increased surveillance with ultrasound screening and CA125; and prophylactic bilateral salpingoophorectomy.

It is important for women to do the following:

  • Be aware of your family history of cancer and record it. Be aware of cancers for at least three generations in your family, both on your mother’s and your father’s side.
  • Inform your physicians about new cancers that develop in your family.
  • If you have a concerning family history of cancer, ensure that your physician is aware and knowledgeable about the latest developments in cancer genetic testing, risk stratification, and risk reduction strategies.
  • Ask for referral to a specialist if necessary.
  • If you have had genetic testing for a cancer predisposition gene, check back with the person who tested you periodically for new updates.

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  • Ruth Woodie February 11, 2013 at 10:57 pm

    Very informative. Thanks so much for sharing.