There are less common hereditary cancer syndromes that confer an increased risk of developing breast cancer. These syndromes may seem a bit more elusive but it is imperative that clinicians assess their patients for their presence because an increased incidence of breast cancer is seen within families that carry these syndromes. Clinicians should be suspicious of these less common hereditary syndromes when three or more findings occur in any of the four following groups:
- Sarcoma, adrenocortical carcinoma, brain tumor
- Endometrial cancer, thyroid cancer, kidney cancer, macrocephaly, skin findings of trichilemmoma, multiple palmoplantar keratosis, multifocal or extensive oral mucosal papillomatosis, multiple cutaneous facial papules
- Diffuse gastric cancer
- Hamartomatous polyps of the gastrointestinal tract
- Patients whose family histories suggest a less common hereditary breast cancer syndrome should also be referred to a genetics professional for genetic counseling. Less common hereditary breast syndromes include Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer.
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Case #1
AB came in for genetic counseling at age 40, due to her concern about her mother’s history of breast cancer at age 44 and her wish to be proactive in surveillance and prevention measures. Her mother’s only sister died at age 60, and her maternal grandmother died at age 86; neither of them had been diagnosed with cancer of any kind. There was also a history of colon cancer in AB’s father at age 62.
AB’s family pedigree, which is a chart that enables a genetics professional to visualize the appearance and phenotype of a particular gene, is shown in Figure 1. Family members affected by breast and colorectal cancer are indicated and standard symbols are used to represent women (circles) and men (squares).
According to guidelines from the National Comprehensive Cancer Network, AB met the criterion for testing hereditary breast and ovarian cancer (a first- or second-degree relative with breast cancer at age 45 or younger). However, due to significant limitations in the ability to interpret test results in an individual without cancer, it is recommended that in any family, testing begin with the family member with the highest likelihood of a mutation. If a mutation is identified in that individual, then other family members can be tested for that specific mutation. If no mutation is detected, then testing is usually not indicated for other family members.
AB’s mother, now age 62, was the ideal candidate for testing, and she agreed to be tested. Analysis revealed a mutation in the BRCA2 gene. It was therefore recommended that she undergo risk-reducing salpingo-oophorectomy and be screened with breast magnetic resonance imaging (MRI) and mammography annually, or consider risk-reducing bilateral mastectomy or other risk-reducing measures. Her initial breast cancer had been treated with lumpectomy followed by radiation therapy.
For AB, the following information was now clear: the cancer in her mother was hereditary, and the specific mutation had been identified. AB was tested for the mutation found in her mother, and the results showed that AB did not inherit the mutation. These results were interpreted as a “true negative.” Her risk for hereditary breast cancer having been ruled out, she was advised that she was expected to have the same risk for breast and ovarian cancer as a woman at average risk and should be screened accordingly. In addition, due to the history of colon cancer in her father, AB was advised to begin screening via colonoscopy at age 40, rather than at age 50.
GG is a 34-year-old woman who has come to the clinic for her annual well woman examination. She has not had a diagnosis of breast cancer, but she is concerned that she is at high risk of developing breast cancer because she has an older sister (GA) who was diagnosed with breast cancer at age 35. She has a younger sister (GB) who was diagnosed with breast cancer at age 31. On the paternal side of her family, she had an aunt who was diagnosed with breast cancer at age 78 and died at age 82.
Why is this patient an appropriate candidate for genetic counseling?
- A known mutation in a breast cancer susceptibility gene within the family
- A family history suggestive of a BRCA mutation
- More than one first-degree relative with breast cancer diagnosed at an age younger than 45
- More than two family members with primary breast cancer
The best answers are C and D. This patient is an appropriate candidate for genetic counseling, because she has 1 or more first-degree relatives who have been diagnosed with breast cancer at age 45 or younger and 2 or more individuals with primary breast cancer on the same side of the family.
You receive a report from the genetic counselor after GG’s appointment. The genetic counselor appropriately recommended which of the following for GG and her family?
- Genetic testing for GG
- No testing at this time
- Genetic testing on a family member who has developed breast cancer
- Tumor testing on GA and GB
The best answer is C. The genetic counselor recommended genetic testing on an affected member of GG’s family.
Subsequently, GG’s older sister GA undergoes genetic testing and is found to have a BRCA1 mutation. The genetic counselor appropriately makes which of the following recommendations for GG and her family?
- No further testing should be done on this family
- Single-site genetic testing for all of GG’s siblings
- Single-site genetic testing for GG and all of her siblings
- Tumor testing for GA to establish risk-reduction recommendations
The best answer is C. Single-site genetic testing for GG and her siblings is the most appropriate next step.
GG’s genetic test results are negative for the familial BRCA1 mutation. As her clinician, what do you recommend?
- Educate GG about the fact that she is considered to be at average risk and should therefore follow recommendations for an average-risk individual.
- Suggest a complete genetic panel for GG because something may have been missed.
- Recommend annual breast magnetic resonance imaging because GG is now considered at elevated risk.
The best answer is A. Education on GG’s status as a woman at average risk should be provided, and guidelines and screening for an average-risk individual should be followed.
