Question 1

Which of the following is not a major phenotypic feature of hereditary breast cancer and ovarian syndrome?&#10;A) A Triple Negative Breast cancer diagnosis before the age of 70.&#10;B) Increased incidence of family members with tumors in specific organs such as the ovaries, pancreas, or prostate.&#10;C) A family member with more than one primary cancer (bilateral tumors) or a single individual diagnosed with both breast and ovarian cancer.&#10;D) A breast cancer diagnosis before the age of 50.

Accepted Answer

It is true that a triple negative breast cancer diagnosis is linked to Hereditary Breast and Ovarian Syndrome, however it is a greatest risk before the age of 60. Hereditary breast and ovarian cancer syndrome is linked to families with family members having ovarian, prostate, and pancreatic tumors; patients with multiple primary cancers and cancer diagnoses in both the breast and ovaries; and early onset breast cancer.

Question 2

Which of the following is true of known genes that are linked to breast cancer?&#10;A) BRCA 1 is found on Chromosome 17 and transmitted through an autosomal dominant pattern and is linked to male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer.&#10;B) If a patient is BRCA gene positive they may never develop a cancer in their lifetime.&#10;C) The inheritance of the BRCA gene always skips generation.&#10;D) If a person is a BRCA gene carrier there is a 100% penetrance rate that the mutation will be passed on to their offspring.

Accepted Answer

BRCA1 and BRCA 2 are germline mutations that begin the process of tumorigenesis. In order for a patient to develop a cancer, they must have a mutation in both copies of BRCA1or BRCA2. If a patient never develops a second mutation, they will not develop a cancer. The BRCA 1 gene is located on chromosome 17 and transmitted in an autosomal dominant pattern. However, BRCA 2, found on chromosome 13, is transmitted autosomal dominant and is linked to male breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer. Both BRCA 1 and BRCA2 are inherited in an autosomal dominant pattern. It can appear that the gene skipped a generation if a carrier does not have a second mutation. There is a 50:50 chance that BRCA gene carriers will pass on the mutation to their offspring.

Question 3

What is the primary risk reducing recommendation for management of patients with a BRCA gene mutation?&#10;A) Strict breast cancer and ovarian cancer surveillance for women and breast and prostate cancer screen in men.&#10;B) Intensive breast cancer screening.&#10;C) Bilateral mastectomy and adjuvant hormonal therapy with Tamoxifen or an aromatase inhibitor.&#10;D) A bilateral salpingo-oophorectomy between ages 35-40.

Accepted Answer

They recommend a risk reducing bilateral salpingo-oophorectomy once childbearing is complete. This procedure has been linked to a significant reduction in ovarian cancer. Strict breast and ovarian cancer surveillance and breast and prostate cancer screen in men are not primary recommendations but can be offered to those who want to delay a surgical approach. Intensive breast cancer screening is offered to those with a BRCA mutation but is not a first recommendation. Bilateral mastectomy and adjuvant hormonal therapy is recommended to women who wish to not undergo as radical of procedure as a bilateral salpingo-oophorectomy. This is also not recommended in women diagnosed with ovarian cancer until 5 years after their ovarian diagnosis.

Question 4

What type of Breast Cancer Screening is best for a woman with a BRCA gene mutation?&#10;A) Self breast exams starting at 18, annual clinical breast exams at age 25, an MRI for breast cancer screening annually beginning at age 25, and breast imaging every 6 months (mammogram or MRI) beginning at age 30.&#10;B) Self breast exams starting at 18, annual clinical breast exams at age 20, an MRI for breast cancer screening annually beginning at age 30, and breast imaging annually (mammogram or MRI) beginning at age 40.&#10;C) Self breast exams starting at 25, annual clinical breast exams at age 35, an MRI for breast cancer screening annually beginning at age 35, and breast imaging every 6 months (mammogram or MRI) beginning at age 40.&#10;D) Self breast exams starting at 20, annual clinical breast exams at age 25, an MRI for breast cancer screening annually beginning at age 35, and breast imaging every 6 months (mammogram or MRI) beginning at age 40.

Accepted Answer

Self breast exams should begin at 18, annual clinical breast exams at 25, an MRI for breast cancer screening annually beginning at age 25, and breast imaging every 6 months beginning at age 30.

Question 5

What is an appropriate screening tool for men with men with both gynecomastia or parenchymal/glandular breast density and a BRCA gene mutation?&#10;A) Chemoprevention&#10;B) Self breast exams with clinical breast exams beginning at age 35.&#10;C) Mammogram annually in addition to CBE and SBE at age 35.&#10;D) No extra testing should be offered.

Accepted Answer

Chemoprevention is not a recommended option for men; this treatment is best used in women who choose not to undergo a prophylactic mastectomy.

Question 6

What breast and ovarian cancer linked syndrome is associated with noncancerous growths known as hamartomas and malignancies such as breast, thyroid, colorectal, kidney and endometrial cancer?&#10;A) Li-Fraumeni Syndrome&#10;B) Cowden Syndrome&#10;C) Peuts-Jeghers Syndrome&#10;D) Hereditary Nonpolyposis Colon Cancer

Accepted Answer

Cowden Syndrome is also known as PTEN Hamartoma Tumor Syndrome. Women that suffer from this syndrome are at a 25%-50% lifetime risk for breast cancer. Li-Fraumeni Syndrome is associated with a germline mutation of the tumor suppressor tumor protein gene TP53 on chromosome 17. It is characterized by premenopausal breast cancer in combination with childhood sarcoma, brain tumors, leukemia, and adrenocortical carcinoma. Peuts-Jeghers Syndrome is a mutation in the STJ11 tumor suppressor gene. This syndrome is associated with dark freckling of the buccal mucosa/axillary/perioral area, hamartomas of the stomach and intestine, and increased risk for breast, ovarian, pancreatic, and gastrointestinal cancers. Hereditary Nonpolyposis Colon Cancer is associated with primary cancers of the colon, endometrium, ovaries, and the stomach.

Question 7

What breast cancer linked syndrome often presents as lobular breast cancer in women and has a lifetime cancer risk 60%?&#10;A) Hereditary Diffuse Gastric Syndrome.&#10;B) Peuts-Jeghers Syndrome&#10;C) Cowden Syndrome&#10;D) Hereditary Nonpolyposis Colon Cancer

Accepted Answer

HDGS is a germline mutation in the cadherin-1 (CDH1) gene that presents as a lobular breast cancer. Peuts-Jeghers Syndrome is a mutation in the STJ11 tumor suppressor gene. This syndrome is associated with dark freckling of the buccal mucosa/axillary/perioral area, hamartomas of the stomach and intestine, and increased risk for breast, ovarian, pancreatic, and gastrointestinal cancers. Women that suffer from Cowden Syndrome are at a 25%-50% lifetime risk for breast cancer and most commonly have hamartomas in the GI tract. Hereditary Nonpolyposis Colon Cancer is associated with primary cancers of the colon, endometrium, ovaries, and the stomach.

Question 8

Based on their risk profile for developing an ipsilateral or contralateral breast cancer, whom should practitioners refer for an ipsilateral mastectomy, a contralateral prophylactic mastectomy, and/or a prophylactic bilateral salpingo-oophorectomy?

A) BRCA positive, postmenopausal patients with a previous cancer diagnosis
B) BRCA positive, premenopausal women with a previous cancer diagnosis.
C) BRCA positive, postmenopausal patient with no personal history of breast cancer.
D) BRCA positive, premenopausal patient with no personal history of breast cancer.

Accepted Answer

BRCA positive, premenopausal women with a previous cancer diagnosis are at the greatest risk for developing a new contralateral cancer or new primary in the ipsilateral breast. BRCA positive, pre-and-postmenopausal patients with no personal history of breast cancer are still at risk and may benefit from one or both of these surgical procedures, but they are not at as great of a risk. BRCA positive, postmenopausal patients with a previous cancer diagnosis will not see the same benefits as premenopausal women.

Question 9

Which of the following will not cause a greater penetrance of the BRCA 1 or BRCA 2 gene mutation?&#10;A) Exposure to carcinogens such as tobacco and hormonal factors.&#10;B) A common genetic mutation for BRCA1 or BRCA 2&#10;C) A rare genetic mutation including Li-Fraumeni Syndrome, Lynch syndrome etc.&#10;D) Radiation exposure at a young age in a BRCA positive male or female.

Accepted Answer

A common genetic mutation for BRCA1 or BRCA 2 will not cause an increase of gene penetrance. Common gene mutations actually have a lower penetrance than a rare genetic mutation. Many environmental factors including hormones, radiation, and tobacco use are linked to increase cancer risk. Rare genetic mutations have a greater penetrance than a common gene mutation. Young women who are BRCA positive women are at a greater risk for developing a radiation induced cancer.

Question 10

What is the term for an accumulation of random genetic changes in an isolated population as a result of its proliferation from only a few parent colonizers?&#10;A) De novo mutation&#10;B) A Kindred&#10;C) A germline mutation&#10;D) The Founder Effect

Accepted Answer

There are 3 mutations that occur at an increased rate in people of Ashkenazi Jewish ancestry and are believed to originate in this population. These genes have also been found in those in families originating from the Netherlands, Hungary, Iceland, Sweden, Italy, France, South Africa, Pakistan, Asia, French Canadians, Hispanics, and African Americans. This pattern represents the founder effect. A De Novo Mutation is defined as mutations that are not inherited, but rather appear first in the affected individual. A kindred is defined as an aggregate of genetically related persons. An example of this is persons of Ashkenazi ancestry. A germline mutation is defined as a change in a gene in the body's reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring.

Deck 7: Hereditary Breast and Ovarian Cancer Syndrome