The majority of patients with hereditary breast and ovarian cancer have mutations in either the BRCA1 or BRCA2 genes. These mutations disrupt the body’s ability to repair DNA, which results in an increased susceptibility to cancer. In these families there are frequently several generations of women affected by breast and ovarian cancer, often at a young age. Other malignancies such as prostate, male breast, melanoma, and pancreatic cancers may also be observed Prevalence
The prevalence of BRCA
mutations varies based on a number of factors. In the United States the chance of a harmful BRCA mutation is 1 in 400 people, however the frequency increases to 1 in 40 in Ashkenazi Jewish patients. Increased frequency in BRCA mutations have been reported worldwide in individuals from: the Netherlands, Sweden, Hungary, Iceland, Italy, France, South Africa, Pakistan, Asia, French Canadians, Hispanics, and African Americans. Risk
The lifetime risk of developing breast and ovarian cancer has been reported as 72% and 44% respectively for patients carrying the BRCA 1 mutation and 69% and 17% for patients carrying the BRCA 2 mutation. With a mean age of diagnosis for breast cancer of 43 years for BRCA 1
patients and 47 years for BRCA 2 patients. Risk of other cancers associated with BRCA mutations are also increased but are not as high as those observed with breast and ovarian cancer. Genetics researchers are continually finding mutations in genes that are linked to developing certain cancers. The following personal and/or family characteristics suggest an individual should be tested for such a mutation: - Breast cancer before the age of 50
- Triple-negative tumor (ER-PR-HER2 negative) in someone younger than 60
- Ashkenazi Jewish heritage and breast cancer at any age
- Two or more breast cancers in one individual
- First-degree relative with breast cancer diagnosed before age 50
- Two
relatives on the same side of the family with breast cancer and/or pancreatic cancer
- Family or personal history of ovarian cancer, fallopian cancer, or primary peritoneal cancer
- Male breast cancer
- Known mutation carrier in the family
Surveillance
For patients who wish to delay surgical risk reduction, breast cancer surveillance and ovarian cancer screening may be offered. Patients should be educated regarding the signs and symptoms of breast, ovarian, and other associated cancers. Breast Evaluation
Beginning at the age of 18 self breast exams may facilitate awareness of changes. Clinical breast exams should be
performed every 6 to 12 months beginning at age 25. Annual Mammography
Mammography should begin at age 30 or 5 years before the earliest age of cancer diagnosis in the family. While the risk of radiation associated breast cancer from mammography is believed to be small it needs to be weighed against the diagnostic benefits of mammograms starting at an earlier age. Magnetic Resonance Imaging (MRI) and Other Modalities
MRI for breast cancer screening is recommended annually beginning at age 25 and should be staggered by 6 months with annual mammograms. Data regarding the role of screening breast ultrasound have not demonstrated additional benefit in BRCA
patients. Ovarian Cancer Screening
BRCA mutation carriers who have not undergone removal of the ovaries may undergo ultrasound and CA-125 blood screening every 6 months beginning at age 30 or 5 to 10 years before the earliest age of a relative diagnosed with ovarian cancer. Men with a BRCA Mutation
There are no proven risk reducing surgical options for male BRCA mutation carriers. Therefore the following screening strategy is recommended: - Monthly breast self exams starting at age 35
- Clinical breast evaluation every 12 months starting at age 35
- Men should discuss with their clinician the role of baseline mammogram at age
40
- Prostate cancer screening starting at age 40
Other Cancer Screening
There is no consensus regarding screening for melanoma or pancreatic cancer. Possible recommendations involve full body skin exams and research trials for pancreatic cancer screening. Guidelines for colon cancer screening in BRCA mutation carriers do not differ from those in the general population. However, if an individual has a family history of colon cancer or a prior adenoma, then more aggressive screening may be recommended. Chemoprevention
Chemoprevention strategies to reduce the risk of cancer have focused on estrogen receptor modulators and aromatase
inhibitors in women at high risk women for breast cancer. The use of oral contraception in women with a BRCA mutation may reduce the risk of ovarian cancer but may increase the risk of breast cancer. Other Mutations
For women who carry mutations in genes other than BRCA that confer moderate risk for breast cancer like PALB2, CHEK2, and ATM the options for breast cancer prevention are similar to BRCA mutation carriers. Mastectomy
Risk reducing removal of both breasts decreases cancer by as much as 90%. However, risk reducing surgery does not completely eliminate the risk of developing cancer. Patient with a BRCA mutation are increasingly being offered skin sparing
mastectomy with or without preservation of the nipple and areola because of superior cosmetic results. Breast Reconstruction
Most patients undergoing prophylactic mastectomy are candidates for immediate breast reconstruction. A greater focus on good cosmetic results is possible in this group of patients who are unlikely to require postoperative chemotherapy or radiation treatment. Surgical techniques such as nipple sparing mastectomy and hidden scar mastectomy can often be utilized. Bilateral Salpingo-Oopherectomy
Patients who carry a BRCA mutation should be referred to a gynecologic oncologist for a discussion about preventative surgeries. Removal of the
fallopian tubes and ovaries is the most effective approach to reduce risk and decreases the risk of ovarian cancer in BRCA patients by 80%. Pre and peri-menopausal women who undergo removal of the ovaries will likely experience side effects of surgically induced menopause. Currently there is limited data on the use of hormone replacement therapy in these patients and how hormone therapy may affect breast cancer risk. Fertility Preservation
Women considering removal of the ovaries who have not completed childbearing should be counseled about alternative reconstructive options. For women who wish to preserve their ability to have a genetic child embryo or oocyte cryopreservation is an
option. Treatment of BRCA carriers with a Personal History of Cancer
Treatment of patients who undergo genetic testing after they have been diagnosed with cancer is more complex. Women who are candidates for breast conservation therapy may opt to undergo double mastectomy to reduce their risk of a second breast cancer. Risk reducing bilateral slapping oophorectomy should be recommended in mutation carriers with a breast cancer diagnosis. Treatment of prostate cancer in men with a BRCA mutation does not differ from sporadic prostate cancer treatment. However, because prostate cancer in BRCA carriers is more aggressive, treatment with surgery or radiation may be recommended instead of active
surveillance. The BRCA Center
Care for patients with a BRCA mutation requires a multidisciplinary team consisting of: breast specialists, breast radiologists, gynecologic oncologists, fertility specialists, plastic surgeons, and genetic counselors. Because of the broad expertise required to deliver comprehensive care patients will ideally be treated in a BRCA Center. About the Author
Dr. Wojciech Dec is a board certified plastic surgeon specializing in breast reconstruction at the NY BRCA Center in Lenox Hill Hospital in New York, NY. For more information please contact the BRCA Center at info@BRCAcenter.com.
|