How Your Genes Affect Breast Cancer
Online Health Chat with Michael Cowher, MD and Ryan Noss MS, LGC
March 21, 2014
Breast cancer is a disease that will affect about 13 percent of women in the United States. With early detection and treatment, the five-year survival rates for breast cancer are promising with an 88 percent rate for those in stage 1. (Rates vary according to stage of cancer and age when found).
Of those patients diagnosed with breast cancer, around 5 percent have a BRCA1 or BRCA2 mutation. Knowing your family history is the first step in the detection of breast cancer. At-risk families can take blood tests to screen for mutations in these genes. However, genetic testing is done only when definitely indicated by a strong personal or family history.
As researchers learn more about the genetics of breast cancer, doctors can diagnose and treat patients based on their specific needs. Effective treatment and rehabilitation for breast cancer is available with significant advancements in recent years. Because of genetic screening—along with the team approach that involves geneticists, surgeons, oncologists, and others—patients are now provided with as much information as possible to make the best decision for them.
About the Speaker
Michael Cowher, MD, is a breast surgeon at Cleveland Clinic. He completed his fellowship in breast surgery at Cleveland Clinic following his residency in general surgery at Allegheny General Hospital, in Pittsburgh, Pa. Dr. Cowher completed medical school at Northeastern Ohio Universities College of Medicine, in Rootstown, Oh. Dr. Cowher is an associate staff physician in the Breast Center, and is also the Quality Improvement Officer of Breast Services at Cleveland Clinic.
Ryan Noss, MS, LGC is a licensed genetic counselor at Cleveland Clinic. He has a special interest in hereditary cancer syndromes, and provides genetic counseling services for hereditary breast cancer at the Cleveland Clinic’s Breast Center. Noss earned his master’s degree in genetic counseling at the University of North Carolina at Greensboro, in Greensboro, NC. He completed his clinical rotation for cancer genetics at the Hereditary Cancer Clinic at Duke University in Durham, NC. Noss is also a clinical supervisor for genetic counseling students at Case Western Reserve University, in Cleveland, Oh.
Let’s Chat About How Your Genes Affect Breast Cancer
Breast Cancer Risk
1HF4: Would it be beneficial for me to be tested for the BRCA mutation? What are causes of breast cancer, and are all of them related to this gene? If I were tested but did not carry the mutation would this mean that I would not get breast cancer?
Ryan_Noss,_MS,_LGC__: There are in fact multiple causes of breast cancer and hereditary reasons account for about 10 percent of cases. Therefore, if you were tested and were normal, this would not rule out the possibility of having breast cancer. In fact, a woman in the general population has about a 12 percent lifetime risk of breast cancer.
mhruler: Are there any particular forms of breast cancer that are associated with BRCA 1 and BRCA 2 mutations?
Michael_Cowher,_MD_: There are, but it is important to remember these are associations, not absolutes. Compared to non-BRCA carriers, BRCA1 positive patients' breast cancers are more likely to be of the basal subtype, high grade, estrogen receptor positive, progesterone receptor positive, Her2 negative, and p53 mutation positive. Compared to non-BRCA carriers, BRCA2 positive patients' cancers tend to be of the luminal subtype, also having higher grade and ER positivity. These are generalities though, and BRCA1 or 2 positive patients do not all have the same forms of breast cancer.
bluebirder: No one that I am aware of in my family has ever had breast cancer. I have two sisters who are 85 and 80 years old and they do not have breast cancer. I am 82 years old. What are my chances of getting it? I get a mammogram every year, and I am of normal weight. I exercise regularly and I am pretty healthy.
Michael_Cowher,_MD_: It appears as though you have minimal—if any—risk factors for the development of breast cancer. The lifetime risk of breast cancer for an average American woman is one in eight—or 12 percent. However, there are more specific risk calculators that take into account individual risk factors—although none of the calculators is perfect. One easy one to use at home is the Gail risk assessment model, available at www.cancer.gov/bcrisktool. You can put in some other easy questions to get a more personalized answer.
asgalian: What is the likelihood that a daughter will have breast cancer if her mother did? Are mammograms and ultrasounds enough to determine the need for further study? I recently had both and then an MRI was also requested. I don't think any of these tests revealed a clear enough picture, so I was advised to get another mammogram in six months. My mother had a mastectomy due to breast cancer.
Ryan_Noss,_MS,_LGC__: The exact likelihood would partially depend upon the age of onset of breast cancer as well as the personal history of the individual. In general, having a mother with breast cancer would increase a person's risk above the general population. Often, the collaboration of a physical exam, mammogram, and ultrasound provide a clear picture to determine the need for further study. However, there are instances such as yours that due to multiple factors further testing is needed.
1HF4: My family history is my mother had breast cancer and died in her 50s. My maternal grandmother had lung cancer and died in her 60s. My maternal grandfather had bone cancer and died in his 80s. My father had esophageal cancer and died in 50s.
Ryan_Noss,_MS,_LGC__: I think from a hereditary standpoint (based on a single gene) I can reassure you that there is a low enough of a likelihood for a BRCA1 or BRCA2 mutation that genetic testing would not be recommended. However, I would share your history of a mother with breast cancer with your primary care physician to discuss a screening plan.
megr: What are my odds of getting cancer again? I had it when I was 57 years old and am now 68 years old.
Michael_Cowher,_MD_: There are multiple factors that play into the risk of having a cancer recurrence including: the type (biology) of cancer you had, the stage, the surgery (mastectomy or lumpectomy), surgical margins, chemotherapy, radiation, and other adjuvant treatments you may have had. For BRCA-negative patients, the odds of developing a new breast cancer are roughly 0.3 percent per year, so three percent every ten years.
megr: I don't understand this, "For BRCA negative patients, the odds of developing a new breast cancer are roughly 0.3 percent per year, so three percent every ten years." Can you explain?
Michael_Cowher,_MD_: It is additive. For a 60-year-old woman who is BRCA negative and has been treated for breast cancer, the odds of her having a new (not recurrence, but elsewhere as in the other breast) breast cancer developing are approximately three percent by age 70, six percent by age 80, and nine percent by age 90.
Breast Cancer Genes
megr: Starting with my maternal grandmother, every female in my family has had breast cancer. I found out I was ER positive at the age of 58 years old. My sister found out she had breast cancer at the age of 51 years old, my mother at 37 years old, my grandmother at 28 years old (and stomach cancer at 60 years old), my mother’s sister (63 years old), and her daughter (53 years old, with triple negative. Her brother had colon cancer at 50 years old). My cousin and myself were tested for the BR genes and we don't have them. I was tested in 2004 and my cousin in 2011. Is there another known gene? Can we donate blood for any studies? We do not qualify for the Dr. Mary-Claire King study. I have a daughter who is 48 years old, as well as a granddaughter. My cousin also has a daughter and granddaughter. My daughter and I alternate every six months with a mammogram and then an MRI. Is there anything else we can do? We both exercise, eat right, and are not overweight.
Ryan_Noss,_MS,_LGC__: There have been recent advances in the knowledge of genes associated with breast cancer as well as the technologies used to test for them. Therefore, there may be further clinical genetic testing available to you regarding your personal and family history of cancer. If you met with a genetic counselor when you had genetic testing in 2004, I would recommend that you contact that genetic counselor to discuss further testing options. If you did not meet with a genetic counselor, I would recommend that you ask your primary care provider to refer you to one. You can schedule an appointment with a genetic counselor in our department with a referral by calling 216.636.1768.
Breast Cancer Association with Ovarian Cancer
mhruler: What are the risks of breast cancer after ovarian cancer in the general population? What are the risks of breast cancer after ovarian cancer if someone is identified with a BRCA mutation?
Ryan_Noss,_MS,_LGC__: For someone with a BRCA mutation, the risk of breast cancer is not significantly altered by the presence of a prior ovarian cancer. The risk of breast cancer in a woman with a BRCA1 or BRCA2 mutation have a lifetime risk between 50 to 85 percent of having breast cancer.
Breast Cancer and Lynch Syndrome
swahumina: I found a lump in my breast when I was 40 years old, which turned out to be stage 2 metaplastic carcinoma breast cancer. I was tested and was found negative for the BRCA 1 and 2 genes. However, my grandmother died of uterine cancer at the age of 30 years old in 1941. She had had a miscarriage, so we do not know if that possibly contributed to her cancer. I do not know much about that side of the family, although my immediate family, uncle, and cousins (all male) from that side are all ok. Based on this information, do you think that I should be tested for any other genes or that I should be worried? While attending the Young Survival Coalition (YSC) conference, nurses from Myriad scared the heck out of me that I may have Lynch Syndrome. My genetic counselor at Cleveland Clinic, Brandi Leach, said that there is not much of a possibility. I trust her, and yet I am afraid. What do you think?
Michael_Cowher,_MD_: I am sorry to hear you had such a bad experience with the person working for Myriad. Based upon the information you provided, I would say the likelihood you have Lynch Syndrome is quite low and would not require genetic testing. Ms. Leach is a fantastic genetic counselor, and actually a national expert in Lynch Syndrome so you are in excellent hands with her!
Oncotype DX® Genetic Testing
NLE : How does Oncotype DX® influence treatment decisions? What do you recommend with an intermediate score?
Michael_Cowher,_MD_: Oncotype DX® for breast cancer is a genetic test on the tumor cells—not your own genetic makeup. Its primary use is in estrogen receptor positive, node negative breast cancer to help determine the benefit of systemic chemotherapy. The recurrence score is used to predict ten year risk of local recurrence. An intermediate recurrence score is associated with a 14.3 percent risk of recurrence at ten years, and is the 'debatable' result. Based on this current evidence, the decision whether or not to provide chemotherapy to a patient with an intermediate recurrence score is best discussed with your oncologist who will take into account your other individual and tumor characteristics.
Genetic Testing Outcomes
megr: What would be the benefit of genetic counseling? If it was done in 2004, what could have changed? I had a mammogram and then an MRI six months later. What would they do different?
Ryan_Noss,_MS,_LGC__: The benefit of genetic counseling would be to discuss what further genetic testing has been available. There have been advances in the technology used to test BRCA1 and BRCA2. If a genetic change were to be found in either gene in newer testing technologies, then, yes, your management options could change.
mhruler: With genetic testing, what percentage of tests results in the following:
1. variants of unknown significance?
2. BRCA or other identified gene mutations known to cause deleterious results?
3. no identified gene mutations?
4. variants that have been researched and are no longer considered "unknown" and not deleterious?
Ryan_Noss,_MS,_LGC__: This is a challenging question as the frequency of variants of unknown significance would vary depending upon the gene in question. In general, the longer a gene has been studied and tested clinically, the fewer variants one would receive. Similarly, the more often a gene is tested the more often a variant would be reclassified. Additionally, the frequency with which a mutation is found or not depends upon the reason for testing. Generally about ten percent of all cases of breast cancer is felt to be due to a change within a single gene.
Treatment for BRCA Positive Patients
megr: What treatment would be applied if the new testing for the BRCA genes showed positive? Again I get mammogram and MRI every year.
Ryan_Noss,_MS,_LGC__: If the testing was positive, you would qualify for consideration of a prophylactic mastectomy—if you were interested. Additionally, this would suggest there is an increased risk for ovarian cancer if you had a BRCA1 or BRCA2 mutation, which would merit either ovarian cancer surveillance or prophylactic surgery (removal of the ovaries prior to developing cancer).
Genetic Testing and Insurance
mhruler: I have a BRCA mutation. I would like my children to be tested. However, they do not want to be tested until they have their families because they are worried about being able to buy life insurance. Is this a realistic concern?
Ryan_Noss,_MS,_LGC__: Currently there is a federal law called the Genetic Information Nondiscrimination Act (GINA) that prevents employers and health insurance providers from using a person's genetic information against them. However, to date this law does not apply to life or disability insurance. Therefore, your children could consider applying for life insurance prior to having testing.
1HF4: My mother passed away at 56 years old of breast cancer that originated on the right side. It metastasized to her brain and lungs, which is what eventually killed her. I have heard that since she died at 56 years old she was too old for my Cleveland Clinic insurance to cover a genetic testing of myself, is that true? If I were to have genetic testing, how would this benefit me in a preventative way? Additionally she had an estrogen-based cancer. Are these more likely to be genetically related, lifestyle or both? If I were to have a double mastectomy would that prevent me from getting breast cancer?
Ryan_Noss,_MS,_LGC__: There are national guidelines indicating scenarios in which genetic testing should be covered an insurance provider. In general, a single person with breast cancer who is in their mid-50s would not meet this criteria. However, depending upon the remainder of the family history and the pathology of the tumor, this may change. If you were to have testing and it identified a mutation, this would alter your medical care in a preventative way by indicated the availability of either more frequent breast cancer screening or prophylactic mastectomy (surgically removing breast tissue prior to developing cancer). Additionally, it would suggest that there is also an increased risk for ovarian cancer. This would merit either surveillance or prophylactic surgery as well. In general, estrogen-positive cancers are less commonly associated with BRCA1 mutations. However, an estrogen-positive breast cancer does not rule out the possibility of it being genetically based. A double mastectomy would decrease a woman's breast cancer risk by about 90 to 95 percent.
Moderator: I'm sorry to say that our time with Dr. Michael Cowher and genetic counselor Ryan Noss is now over. Thank you both for taking the time to answer questions today.
Michael_Cowher,_MD_: Thank you all for the great questions!
Ryan_Noss,_MS,_LGC__: You are very welcome. Take care!
To make an appointment with Dr. Michael Cowher or any of the specialists in the Breast Center at Cleveland Clinic, please call 216.444.3024. You can also visit us online at www.clevelandclinic.org/breastcenter.
Ask your doctor if a referral to genetic counseling is right for you. If you do not have a primary care provider, please call us to learn about other options for scheduling an appointment.
For an appointment or information, call the Center for Personalized Genetic Healthcare at 216.636.1768 or 800.998.4785. If your doctor is not part of the Cleveland Clinic health system, please have relevant medical records faxed to 216.445.6935.
For More Information
On Genetics and Breast Cancer
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On Cleveland Clinic
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