Mo Salhab MD, MRCS, MS, PG Dip, FRCS
Oncoplastic, Reconstructive & Aesthetic Breast Surgeon
Mr Salhab has teamed up with BRCATESTUK to offer Breast Cancer gene testing using the Color system. The Test cost £395. A follow up consultation maybe required too. Test results will be available in 3-4 weeks after your sample arrives color.
Click on the color test box for more information about the test
If you are considering genetic testing for cancer risk in view of a personal or a family history of cancer, you can make an appointment with Mr Salhab at the Yorkshire Clinic (Sec: 01274550842 or through clinic bookings on 01274 550620)
Genetic testing looks for specific inherited changes (mutations) in a person’s genes. Mutations can be harmful and may increase a person’s chance, or risk, of developing a disease such as breast cancer. Inherited genetic mutations can increase a person’s risk of developing cancer through a variety of mechanisms, depending on the function of the
gene. Mutations in genes that control cell growth and the repair of damaged DNA are particularly likely to be associated with increased cancer risk.
Breast cancer Risk
Current evidence suggests that one out of every eight women born today will be diagnosed with breast cancer at some time during her life. This means that women with no known family history or faulty genes will have approximately 12-13% risk for developing breast cancer.
Mr Salhab will assess your individual risk according to your family history and other factors. After assessment, he will advise you about your risk compared to the average woman. if you were found to be at higher risk of developing breast cancer, risk reducing options will be discussed in details such as more frequent screening using mammograms and or MRI scans, chemoprevention using Tamoxifen, risk reducing surgery and your suitability for gene testing.
Breast screening by mammography can be arranged privately at the Yorkshire clinic, Contact Bev (Mr Salhab Sec on 01274550842 or Clinic Bookings on 01274550620) This service cost £178 and includes detailed assessment and examination by Mr Salhab followed by a mammogram with immediate reporting.
Factors that increase a woman’s risk of breast cancer
Hereditary cancer syndromes
The genetic basis of Hereditary Breast and Ovarian Cancer syndrome (HBOC) is an inherited mutation in either the BRCA1 or BRCA2 genes. Normally, the proteins produced by the BRCA1 and BRCA2 genes prevent cells from becoming malignant by aiding in the repair of mutations in other genes Therefore, an inherited mutation in either of these genes greatly increases the probability of a cell becoming cancerous.
Women with HBOC due to mutations in BRCA1 or BRCA2 have a greatly increased risk for both breast and ovarian cancer. Men with HBOC have an increased risk for male breast cancer and prostate cancer. Both men and women with HBOC may also have an increased risk for pancreatic cancer and melanoma. These cancers are often diagnosed at younger ages than are usually seen in the general population. A small proportion of apparent cases of HBOC may be due to inherited mutations in genes other than BRCA1 and BRCA2. Some candidate genes, such as RAD51C and BRIP1.
Recently inherited mutations in the PALB2 gene are found to be associated with a risk of breast cancer nearly as high as that associated with inherited BRCA1 and BRCA2 mutations. it is estimated that 33 percent of women who inherit a harmful mutation in PALB2 will develop breast cancer by age 70 years. The estimated risk of breast cancer associated with a harmful PALB2 mutation is even higher for women who have a family history of breast cancer: 58 percent of those women will develop breast cancer by age 70 years
Although harmful mutations in BRCA1 and BRCA2 are responsible for the disease in nearly half of families with multiple cases of breast cancer and up to 90 percent of families with both breast and ovarian cancer, mutations in a number of other genes have been associated with increased risks of breast and/or ovarian cancers. These other genes include several that are associated with the inherited disorders Cowden syndrome, Peutz-Jeghers syndrome, Li-Fraumeni syndrome, and Fanconi anemia, which increase the risk of many cancer types.
BRCA1 and BRCA2: Cancer Risk and Genetic Testing
A woman’s lifetime risk of developing breast and/or ovarian cancer is greatly increased if she inherits a harmful mutation. According to the most recent estimates, 55 to 65 % of women who inherit a harmful BRCA1 mutation and around 45 % of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years.
About 1.3 % of women in the general population will develop ovarian cancer sometime during their lives. By contrast, according to the most recent estimates, 39 percent of women who inherit a harmful BRCA1 mutation and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years
Who should consider genetic testing for BRCA1 and BRCA2 mutations?
Because harmful BRCA1 and BRCA2 gene mutations are relatively rare in the general population, most experts agree that mutation testing of individuals who do not have cancer should be performed only when the person’s individual or family history suggests the possible presence of a harmful mutation in BRCA1 or BRCA2.
Factors that are associated with an increased likelihood of having a harmful mutation in BRCA1 or BRCA2 are:
When an individual has a family history that is suggestive of the presence of a BRCA1 orBRCA2 mutation, it may be most informative to first test a family member who has cancer if that person is still alive and willing to be tested. If that person is found to have a harmful BRCA1 or BRCA2 mutation, then other family members may want to consider genetic counseling to learn more about their potential risks and whether genetic testing for mutations in BRCA1 and BRCA2 might be appropriate for them.
If it is not possible to confirm the presence of a harmful BRCA1 or BRCA2 mutation in a family member who has cancer, it is appropriate for both men and women who do not have cancer but have a family medical history that suggests the presence of such a mutation to have genetic counselling for possible testing.
Some individuals—for example, those who were adopted at birth—may not know their family history. In cases where a woman with an unknown family history has an early-onset breast cancer or ovarian cancer or a man with an unknown family history is diagnosed with breast cancer, it may be reasonable for that individual to consider genetic testing for a BRCA1 or BRCA2 mutation. Individuals with an unknown family history who do not have an early-onset cancer or male breast cancer are at very low risk of having a harmful BRCA1 or BRCA2 mutation and are unlikely to benefit from routine genetic testing.
Professional societies do not recommend that children, even those with a family history suggestive of a harmful BRCA1 or BRCA2 mutation, undergo genetic testing for BRCA1 or BRCA2. This is because no risk-reduction strategies exist for children, and children's risks of developing a cancer type associated with a BRCA1 or BRCA2 mutation are extremely low. After children with a family history suggestive of a harmful BRCA1 or BRCA2 mutation become adults, however, they may want to obtain genetic counseling about whether or not to undergoing genetic testing.
What does a positive BRCA1 or BRCA2 genetic test result mean?
BRCA1 and BRCA2 gene mutation testing can give several possible results: a positive result, a negative result, or an ambiguous or uncertain result.
A positive test result indicates that a person has inherited a known harmful mutation in BRCA1 or BRCA2 and, therefore, has an increased risk of developing certain cancers. However, a positive test result cannot tell whether or when an individual will actually develop cancer. For example, some women who inherit a harmful BRCA1 or BRCA2 mutation will never develop breast or ovarian cancer.
A positive genetic test result may also have important health and social implications for family members, including future generations. Unlike most other medical tests, genetic tests can reveal information not only about the person being tested but also about that person’s relatives:
Both men and women who inherit a harmful BRCA1 or BRCA2 mutation, whether or not they develop cancer themselves, may pass the mutation on to their sons and daughters. Each child has a 50 % chance of inheriting a parent’s mutation.
What does a negative BRCA1 or BRCA2 test result mean?
A negative test result can be more difficult to understand than a positive result because what the result means depends in part on an individual’s family history of cancer and whether a BRCA1or BRCA2 mutation has been identified in a blood relative.
If a close (first- or second-degree) relative of the tested person is known to carry a harmful BRCA1 or BRCA2 mutation, a negative test result is clear: it means that person does not carry the harmful mutation that is responsible for the familial cancer, and thus cannot pass it on to their children. Such a test result is called a true negative. A person with such a test result is currently thought to have the same risk of cancer as someone in the general population.
If the tested person has a family history that suggests the possibility of having a harmful mutation in BRCA1 or BRCA2 but complete gene testing identifies no such mutation in the family, a negative result is less clear. The likelihood that genetic testing will miss a known harmful BRCA1 or BRCA2 mutation is very low, but it could happen. Moreover, scientists continue to discover new BRCA1 and BRCA2 mutations and have not yet identified all potentially harmful ones. Therefore, it is possible that a person in this scenario with a "negative" test result actually has an as-yet unknown harmful BRCA1 or BRCA2 mutation that has not been identified.
It is also possible for people to have a mutation in a gene other than BRCA1 or BRCA2 that increases their cancer risk but is not detectable by the test used. People considering genetic testing for BRCA1 and BRCA2 mutations may want to discuss these potential uncertainties with a genetic counsellor before undergoing testing.
What does an ambiguous or uncertain BRCA1 or BRCA2 test result mean?
Sometimes, a genetic test finds a change in BRCA1 or BRCA2 that has not been previously associated with cancer. This type of test result may be described as “ambiguous” (often referred to as “a genetic variant of uncertain significance”) because it is not known whether this specific gene change affects a person’s risk of developing cancer.
As more research is conducted and more people are tested for BRCA1 and BRCA2 mutations, scientists will learn more about these changes and cancer risk. Genetic counselling can help a person understand what an ambiguous change in BRCA1 or BRCA2 may mean in terms of cancer risk. Over time, additional studies of variants of uncertain significance may result in a specific mutation being re-classified as either harmful or clearly not harmful.
What are the implications of having a harmful BRCA1 or BRCA2 mutation for breast and ovarian cancer prognosis and treatment?
There is some evidence that, over the long term, women who carry these mutations are more likely to develop a second cancer in either the same (ipsilateral) breast or the opposite (contralateral) breast than women who do not carry these mutations. Thus, some women with a harmful BRCA1 or BRCA2 mutation who develop breast cancer in one breast opt for a bilateral mastectomy, even if they would otherwise be candidates for breast-conserving surgery. In fact, because of the increased risk of a second breast cancer among BRCA1 and BRCA2 mutation carriers, some doctors recommend that women with early-onset breast cancer and those whose family history is consistent with a mutation in one of these genes have genetic testing when breast cancer is diagnosed.
Breast cancers in women with a harmful BRCA1 mutation are also more likely to be "triple-negative cancers" (i.e., the breast cancer cells do not have estrogen receptors, progesterone receptors, or large amounts of HER2/neu protein), which generally have poorer prognosis than other breast cancers.
Related cancer types: Breast cancer, soft tissue sarcoma, osteosarcoma (bone cancer), leukemia, brain tumours, adrenocortical carcinoma (cancer of the adrenal glands), and other cancers
Related cancer types: Breast, thyroid, endometrial (uterine lining), and other cancers
Genes: MSH2, MLH1, MSH6, PMS2, EPCAM
Related cancer types: Colorectal, endometrial, ovarian, renal pelvis, pancreatic, small intestine, liver and biliary tract, stomach, brain, and breast cancers
The above information is taken from the National Cancer Institute website (http://www.cancer.gov)