Triple Negative Breast Cancer
Women who have a BRCA1 gene mutation tend to get breast cancers that are triple negative .
Triple negative breast cancers are:
- Estrogen receptor-negative
BRCA2 carriers tend to have breast cancers that are estrogen receptor-positive .
What Do Brca1 And Brca2 Genetic Test Results Mean
BRCA1 and BRCA2 mutation testing can give several possible results: a positive result, a negative result, or a variant of uncertain significance result.
Positive result. A positive test result indicates that a person has inherited a known harmful variant in BRCA1 or BRCA2 and has an increased risk of developing certain cancers. However, a positive test result cannot tell whether or when the tested individual will develop cancer. Some people who inherit a harmful BRCA1 or BRCA2 variant never develop cancer.
A positive test result may also have important implications for family members, including future generations.
- Both men and women who inherit a harmful BRCA1 or BRCA2 variant, whether or not they develop cancer themselves, may pass the variant to their children. Each child has a 50% chance of inheriting a parents variant.
- All blood relatives of a person who has inherited a harmful BRCA1 or BRCA2 variant are at some increased risk of having the variant themselves. For example, each of that persons full siblings has a 50% chance of having inherited the variant as well.
- Very rarely, an individual may test positive for a harmful variant not inherited from either parent. This is called a de novo variant. Such a variant is one that arose in a germ cell of one of the parents and is present in all the cells of the person who grew from that cell. The children of someone with a de novo variant are at risk of inheriting the variant.
Having Radiation To Your Chest
Women who were treated with radiation therapy to the chest for another cancer when they were younger have a significantly higher risk for breast cancer. This risk depends on their age when they got radiation. The risk is highest for women who had radiation as a teen or young adult, when the breasts were still developing. Radiation treatment in older women does not seem to increase breast cancer risk.
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How Is Hboc Identified
Mutations in the BRCA1 or BRCA2 genes can be identified through a blood or saliva test. The usual method of testing, called standard gene sequencing, can find most BRCA mutations. There are other types of mutations called rearrangements, which include deletions or duplications in BRCA1 and BRCA2 that also may cause an increased risk for these cancers. Testing is also available for large rearrangements in BRCA1 and BRCA2.
After initial BRCA1 and BRCA2 genetic testing, additional testing may be recommended if:
- The results were negative, meaning no genetic mutation was detected
- A variant of uncertain significance was detected, which means that there is a genetic change, but it is not known how that change could affect cancer risk
Talk with your health care team and/or a genetic counselor for more information.
Most, but not all, insurance providers, including Medicare and Medicaid, cover the cost of complete BRCA1 and BRCA2 testing. Many genetic specialists offer multigene panels, which may include 6, 20, 40, or more genes depending on your personal and family history. The multigene panel tests may often be done at the same time as BRCA1 and BRCA2 testing. Talk with your genetic counselor for more information on the type of testing you will have and your insurance coverage before testing begins.
Genetic Mutations Linked To Breast Cancer
- You have blood relatives on either your mother’s or father’s side of the family who had breast cancer diagnosed before age 50.
- There is both breast and ovarian cancer on the same side of the family or in a single individual.
- You have a relative with triple-negative breast cancer.
- There are other cancers in your family in addition to breast, such as prostate, melanoma, pancreatic, stomach, uterine, thyroid, colon, and/or sarcoma.
- Women in your family have had cancer in both breasts.
- You are of Ashkenazi Jewish heritage.
- You are Black and have been diagnosed with breast cancer at age 35 or younger.
- A man in your family has had breast cancer.
- There is a known breast cancer gene mutation in your family.
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Challenges And Future Directions For Clinical Development In Cancers Other Than Breast And Ovarian
There is considerable interest in the clinical development of PARPi for use in solid tumors other than breast and ovarian cancers. The optimal dose, scheduling, and sequencing of PARPi, and combination with other cytotoxic or biologic agents need to be evaluated in carefully designed clinical trials. The incorporation of predictive biomarkers into studies of gBRCAm and BRCA-like cancers presents challenges. First is the development of a mechanism with which to identify patients who are most likely to benefit from PARPi therapy. Predictive biomarkers applied to readily available bioresources, such as archival tissue or non-tumor tissue, have been proposed. Changes in or baseline PAR incorporation into PBMC DNA was suggested and evaluated as a putative early on-treatment pharmacodynamic measure while present, there was no relationship to clinical outcome . BRCA1/2 somatic mutation or promoter methylation, ATM mutation, MRE11-dominant negative mutations in MMR-deficient cancers, FANCF promotor methylation and PTEN deficiency are all potential biomarkers of sensitivity to PARPi . Importantly, not all patients with deficiencies in BRCA1 or 2 are responsive to PARP inhibition . Therefore, identification and validation of predictive biomarkers of those gBRCAm who will respond to PARPi is also an important area of ongoing research.
What Is My Cancer Risk If I Test Positive For A Brca Mutation
It is high. Having a BRCA mutation means you have a likelihood of 45% to 85% for developing breast cancer in your lifetime, along with a 10% to 46% chance of ovarian cancer, Euhus says.
Thats considerably more than the probability of breast cancer among the general population, which is about 12%, or about one in eight. Ovarian cancer is rarer, affecting less than 1% of the general U.S. population.
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Breast Cancer Risk In Women With Brca1 And Brca2 Inherited Gene Mutations
Women who have a BRCA1 or BRCA2 inherited gene mutation have an increased risk of breast cancer .
BRCA1/2 gene mutations are thought to explain a large portion of hereditary breast cancers .
Most breast cancers, however, are not related to inherited gene mutations.
A woman who has a BRCA1/2 inherited gene mutation may be called a BRCA1/2 carrier.
How This Study Was Done
- 2,195 were diagnosed with breast cancer during the WHI
- 2,322 had not been diagnosed with breast cancer as of Sept. 20, 2017
- half were older than 73 when they were diagnosed and half were younger
- 66.3% were white
- half were older than 81 at the last follow-up visit and half were younger
- 84.9% were white
- likely pathogenic
- uncertain significance
- 148 who had been diagnosed with breast cancer
- 93 who had not been diagnosed with breast cancer
- 3.55% of women who had been diagnosed with breast cancer
- 1.29% of women who had not been diagnosed with breast cancer
- 2.21% of women diagnosed with breast cancer when they were younger than 65 had a BRCA1 or BRCA2 mutation
- 1.09% of women diagnosed with breast cancer when they were age 65 or older had a BRCA1 or BRCA2 mutation
- 30.8% of women diagnosed with breast cancer met NCCN genetic testing guidelines
- 20% of women not diagnosed with breast cancer met NCCN genetic testing guidelines
- 34% of women diagnosed with breast cancer met NCCN genetic testing guidelines
- 16% of women who had not been diagnosed with breast cancer met NCCN genetic testing guidelines
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Brca Mutation: What You Need To Know
- BRCA gene mutations can occur in women and men and be inherited by their biological children.
- Men with the mutation are more likely to be silent carriers women are more likely to develop cancer.
- BRCA1 and BRCA2 account for about half of the families with an identifiable genetic cause of inherited cancers. Other inherited breast cancers are related to less common gene mutations, such as PALB2, ATM, CHEK2, CDH1, STK11, PTEN, TP53 and NF1.
- Getting tested and working with your doctor on preventive steps can lower your cancer risk, even if you are BRCA1- or BRCA2-positive.
Support For People With Inherited Gene Mutations
Some support groups are tailored to people with BRCA1, BRCA2 or other high-risk gene mutations and those with breast cancers related to inherited gene mutations.
Our Support section offers a list of resources to help find local and online support groups. For example, FORCE is an organization that offers online support for people at higher risk of breast, ovarian or other cancers related to family history or inherited gene mutations.
Sharsheret offers online support for Jewish women affected by hereditary breast and/or ovarian cancer.
Susan G. Komen® Support Resources
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Why Brca Gene Mutations Matter
Not every woman who has a BRCA1 or BRCA2 gene mutation will get breast or ovarian cancer, but having a gene mutation puts you at an increased risk for these cancers.
- About 50 out of 100 women with a BRCA1 or BRCA2 gene mutation will get breast cancer by the time they turn 70 years old, compared to only 7 out of 100 women in the general United States population.
- About 30 out of 100 women with a BRCA1 or BRCA2 gene mutation will get ovarian cancer by the time they turn 70 years old, compared to fewer than 1 out of 100 women in the general U.S. population.
If you have a family history of breast cancer or inherited changes in your BRCA1 and BRCA2 genes, you may have a higher breast cancer risk. Talk to your doctor about these ways of reducing your risk
- Prophylactic mastectomy .
- Prophylactic salpingo-oophorectomy .
It is important that you know your family history and talk to your doctor about screening and other ways you can lower your risk. For more information about breast cancer prevention, visit Breast Cancer : Prevention.external icon
Percentage Of Women With Breast Cancer In The Us Who Have A Brca1 Or Brca2 Inherited Gene Mutation
The table below shows the prevalence of BRCA1/2 inherited gene mutations in women diagnosed with breast cancer, by ethnic group .
Percentage of U.S. women with breast cancer who have a BRCA1 or BRCA2 inherited gene mutation, by ethnic group
Adapted from National Cancer Institute materials and Malone et al. .
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Cancers Caused By Mutation
Having a BRCA2 mutation is different than BRCA1 mutations and raises the risk of several different types of cancer. At the current time, however, our knowledge is still growing and this may change in time. Cancers which are more common in people with BRCA2 mutations include:
People who inherit two copies of a mutated BRCA2 gene, in addition to the cancers above, are more likely to develop solid tumors in childhood and acute myeloid leukemia.
Screening guidelines recommend that all people have a screening colonoscopy at the age of 50.
Who Should Consider Genetic Testing For Brca1 And Brca2 Inherited Gene Mutations
Genetic testing is only recommended for people with a high risk of having a BRCA1/2 inherited gene mutation , including those with :
- A family member with a BRCA1/2 inherited gene mutation
- A personal history of breast cancer at age 45 or younger
- A personal history of triple negative breast cancer diagnosed at any age
- A personal history of lobular breast cancer at any age, and a personal or family history of diffuse gastric cancer
- Ashkenazi Jewish heritage and a personal history of breast cancer
- A personal history of breast cancer at age 46-50 and a close family member diagnosed with breast cancer at any age
- A personal history of breast cancer at age 51 or older and a close family member diagnosed with breast cancer at age 50 or younger
- A personal history of breast cancer at age 51 or older and 2 or more close family members diagnosed with breast cancer or prostate cancer at any age
- A close family member diagnosed with breast cancer at age 45 or younger
- A close family member diagnosed with ovarian cancer, pancreatic cancer or metastatic prostate cancer at any age
- A personal or family history of male breast cancer
In most cases, testing for BRCA1/2 inherited gene mutations is first done on the person with breast, ovarian, pancreatic or prostate cancer.
- If no mutation is found, the cancer was not due to a BRCA1/2 gene mutation.
- If a BRCA1/2 gene mutation is found, other family members can be tested for the specific mutation.
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What Are My Options If I Have A ‘cancer Gene’
Women in high-risk categories and those who have the genes linked with breast cancer should consider starting regular breast cancer screening at age 25, or 10 years earlier than the age of the youngest relative with breast cancer at the time of their diagnosis.
Get to know how your breasts look and feel. If you notice any changes, see your doctor right away. And talk with your doctor about blood tests, pelvic exams, and transvaginal ultrasound to look for ovarian cancer.
Some women choose to have a preventive mastectomy to lower their chances of breast cancer. ItÃ¢â¬â¢s also possible to have your ovaries and fallopian tubes taken out. This doesnÃ¢â¬â¢t get rid of all risk, but it does significantly lower it.
Another approach includes using anti-estrogen drugs:
- Tamoxifen, useful in premenopausal and post-menopausal women
- Raloxifene , used to treat osteoporosis useful only in post-menopausal women
- Exemestane , an aromatase inhibitor useful only in post-menopausal women
Ovarian Cancer And Other Cancers
BRCA1 and BRCA2 mutations increase a womans risk of ovarian cancer, pancreatic cancer and melanoma .
BRCA1/2 mutations may also increase the risk of other cancers . However, data are limited and these topics are still under study.
For a summary of research studies on BRCA1 and BRCA2 mutations and cancer, visit the Breast Cancer Research Studies section.
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Overview Of Breast Cancer Risk And Management Among Brca Mutation Carriers
Women who inherit a deleterious germline BRCA1 or BRCA2 mutation face high lifetime risks of developing breast cancer by age 80, which are estimated at 72% and 69%, respectively . Once diagnosed with invasive breast cancer, these women have a high risk of developing a second ipsilateral or contralateral breast cancer . Women with an inherited mutation in either gene are also at a significantly elevated risk of developing ovarian cancer .
BRCA1-associated breast cancers exhibit the pathological features of an aggressive phenotype, and are usually hormone receptor-negative, whereas BRCA2-assocated breast cancers tend to resemble sporadic cancers, and are predominantly hormone receptor-positive . A study compared the survival experience of BRCA2 mutation carriers and non-carriers. BRCA2 mutation carriers who were estrogen receptor-positive experienced a significantly worse survival compared to those with estrogen receptor-negative disease . Metcalfe et al. also reported a worse prognosis for estrogen receptor-positive versus estrogen receptor-negative BRCA2-associated breast cancer . BRCA1 mutation carriers with breast cancer may benefit from treatment with oophorectomy , cisplatinum , or olaparib compared to those without a mutation. This data collectively indicates the importance role of BRCA mutation status with respect to treatment decisions that may impact outcome.
How Common Is Hboc
Most breast and ovarian cancers are sporadic, meaning they occur by chance with no known cause. Most women who have breast or ovarian cancer do not have HBOC.
Currently, it is estimated that less than 1% of the general population has a mutation in the BRCA1 or BRCA2 genes, and up to 10% of women and 20% of men diagnosed with breast cancer have a mutation in 1 of these genes. About 10% to 30% of women younger than 60 diagnosed with triple-negative breast cancer, which are cancers that do not have receptors for estrogen, progesterone, and HER2, have a BRCA1 or BRCA2 gene mutation, and others will have mutations in other breast cancer risk genes. Therefore, doctors recommend that women with triple-negative breast cancer receive genetic counseling and genetic testing .
HBOC is most common in families who have had multiple cases of breast cancer and/or ovarian cancer on the same side of the family. In families with 4 or more cases of breast cancer diagnosed before age 60, the chance of HBOC is about 80%. To compare, the chance of finding HBOC when only 1 woman has had breast cancer diagnosed before age 50 is estimated to be 10% or less.
Families with Ashkenazi Jewish ancestry have an increased chance of having HBOC. There are 3 specific gene mutations, known as founder mutations, that are common in these families:
185delAG in BRCA1
5382insC in BRCA1
6174delT in BRCA2
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