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Can Triple Negative Breast Cancer Be Hereditary

What Is The Risk For Triple

Ask the Expert: Triple Negative Breast Cancer

The disease can affect anyone, but is more likely to show up in those who are:

  • Younger than age 50 .
  • Black or Latinx.
  • Living with a genetic condition called BRCA mutation that increases the risk for breast cancer and other forms of cancer. Most cancers diagnosed in people with the BRCA1 mutation are triple negative.

Study: New Genes Linked With Triple

A research study identified new genes that may be associated with a higher risk for triple-negative breast cancer.

This image is an example of the kind of gel pictures researchers use to understand the order, or sequence, of genes or to look for mutations in genes.

This image is an example of the kind of gel pictures researchers use to understand the order, or sequence, of genes or to look for mutations in genes.

Out of 100 people with breast cancer about 15 will have triple-negative breast cancer . Its one of the most challenging types of breast cancer to treat due to several things:

  • TNBC tends to be more aggressive than other common types of breast cancer.
  • Women usually dont learn they have it until the cancer has already spread to other parts of the body .
  • Treatment options remain limited. Hormone therapies and targeted therapies that help treat people with some types of breast cancer, typically dont work for a woman with TNBC. Doctors use chemotherapy to treat these patients, but it isnt very effective and may have side effects.

If doctors had a way to identify women at risk for TNBC, they might be able to find cancer earlier and before it spreads when it might be easier to treat. And, if doctors had a way to personalize treatment for women with TNBC, they might be able to improve a womans outlook . One approach researchers are using to identify women at risk for TNBC and possible treatment options for TNBC is by studying inherited changes in cancer genes.

Common Susceptibility Loci For Brca1 Mutation Carriers

Because TNBC and breast cancer in BRCA1 mutation carriers are phenotypically similar, studies of genetic modifiers of breast cancer risk in BRCA1 mutation carriers have provided further insight into the genetic risk factors for TNBC. Specifically, SNPs in the 19p13.1 locus that displayed genome-wide significant associations with breast cancer in a GWAS of BRCA1 mutation carriers have also been associated with TNBC risk in the general population . In BCAC and TNBCC combined, the 19p13.1 locus was associated with TNBC risk but was not associated with the risk of ER-positive or ER-negative nontriple-negative breast cancer . Furthermore, these variants seemed to be specifically associated with tumors that were positive for the basal markers CK5/6 or EGFR , indicating specificity for the basal subtype. In addition, variants in ESR1, PTHLH, TOX3, CASP8, and TERT are also associated with both TNBC and the risk of breast cancer in BRCA1 carriers . Of the known TNBC risk factors, only RAD51L1 was not found to be a modifier of BRCA1-related breast cancer risk . Recent data also show that BRCA2 ER-negative tumors have pathologic characteristics similar to BRCA1 ER-negative tumors . Thus, further studies of BRCA1 and BRCA2 breast tumors, stratified by ER or triple-negative tumor status, may provide additional valuable insight into genetic susceptibility to TNBC.

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Benefits Of Genetic Testing For Triple

The current guidelines from the National Comprehensive Cancer Network state that women should be referred for genetic counseling if they:

  • Have been diagnosed with triple-negative breast cancer before age 60
  • Were diagnosed with any type of breast cancer at or before age 50
  • Have a close family member, such as a mother, grandmother, or sister, who has been diagnosed with breast cancer or ovarian cancer
  • Have been diagnosed with two separate breast cancers

If a patient is referred for genetic counseling, the counselor will conduct a detailed review of her family history to determine whether she might benefit from genetic testing. We currently test for a number of known genetic mutations, including mutations to the BRCA1 and BRCA2 genes, which are known to greatly increase a womans risk for breast cancer. With the newly discovered mutations from the previously mentioned study, we potentially can add additional mutations to our routine screening and get a better idea of how likely a woman is to develop another triple-negative breast cancer. Patients who are found to be at high risk might benefit from more intensive screening with the addition of breast magnetic resonance imaging tests to standard mammogram so we can find the disease earlier.

New research indicates more women with triple-negative #breastcancer could benefit from #genetictesting. via @MedStarWHC

The Current Genetic Landscape Of Triple


Shuwei Li, Hsiao-Mei Lu, Mary Helen Black

Ambry Genetics

Correspondence to:

Received: 13 October 2018 Accepted: 29 October 2018 Published: 30 October 2018.

doi: 10.21037/jlpm.2018.10.04

Since the discovery of the BRCA1 and BRCA2 genes, multiple predisposition genes have been identified and included on genetic testing panels for breast cancer . In fact, breast cancer is now recognized as a heterogeneous disease with a complex genetic architecture . However, the full spectrum of genetic variation contributing to triple-negative breast cancer , an aggressive breast cancer subtype, has not yet been fully elucidated. TNBC, which accounts for 1025% of breast tumors, is characterized by absence of expression of the estrogen receptor , progesterone receptor and lack of amplification of the human epidermal growth factor receptor 2 . Patients with TNBC do not benefit from hormonal or anti-HER2 therapy, and exhibit high recurrence risk and poor survival rate in the first 5 years following diagnosis . TNBC patients usually have an early onset of disease and positive family history of breast and/or ovarian cancer, suggesting a strong association with genetic factors . Emerging studies also suggest TNBC may have a genetic risk profile different from other subtypes of breast cancer . Establishing the genetic landscape of TNBC and identifying actionable mutations may lead to better clinical management and therapy response prediction for this aggressive and difficult-to-treat subtype.

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Symptoms Of Triple Negative Breast Cancer

The symptoms of triple negative breast cancer are similar to other breast cancer types.

Symptoms can include:

  • a new lump or thickening in your breast or armpit
  • a change in size, shape or feel of your breast
  • skin changes in the breast such as puckering, dimpling, a rash or redness of the skin
  • fluid leaking from the nipple in a woman who isnt pregnant or breast feeding
  • changes in the position of nipple

Make an appointment to see your GP if you notice anything different or unusual about the look and feel of your breasts.

Determining Risk Of Recurrence In Triple

A personalized prognosis for patients diagnosed with triple-negative breast cancer was the goal of a new study by Katherine Varley, PhD, researcher at Huntsman Cancer Institute and assistant professor of oncological sciences at the University of Utah.

Twenty percent of women diagnosed with breast cancer in the United States will learn they have triple-negative breast cancer. That diagnosis means the three most common proteins known to fuel breast cancer growthestrogen receptor, progesterone receptor, and HER2are not present in the tumor. Those patients will not respond to any of the targeted therapies developed to treat breast cancer with those characteristics. After surgery, their only treatment option is chemotherapy. Targeted therapy allows healthy cells to survive, but chemotherapy can kill normal cells when eliminating the cancer cells.

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Characteristics Of Study Population

Among the 8753 TNBC patients from the clinical cohort, 5498 were Caucasian and 1271 were African American . In contrast, 2095 from the TNBCC cohort were Caucasian . The mean age at diagnosis was 49.8 years for the clinical cohort and 50.8 years for the TNBCC cohort . In addition, 51.9% of the clinical cohort but only 21.9% of the 2148 TNBCC patients reported a first- or second-degree relative with breast cancer .

Tnbc And Family History

Gene Expression in Triple Negative Breast Cancer Samples – ASHG 2014

In a large targeted sequencing study of mainly Caucasian TNBC patients, a positive family history was reported in 539 of 1,510 unselected TNBC cases . In this study, family history was defined as positive when at least 1 first- or second-degree relative was affected by breast cancer or ovarian cancer. In a cohort of unselected Hispanic women with TNBC, 56 of 146 reported breast cancer in first- or second-degree relatives . Concordant results were shown in an investigation of 207 unselected TNBC patients with different ethnicities . In this study, a family history of breast or ovarian cancer was reported in 76 of 207 cases, with a positive family history being defined as 1 close blood relative with breast cancer at age 50 years, or 1 close blood relative with ovarian cancer . Apart from the different ethnicities and the slightly different definitions of a positive family history applied in these studies, there is compelling evidence that more than one-third of all TNBC patients have a familial background of breast and/or ovarian cancer when first- and second-degree relatives are taken into account.

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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

How Fast Can Breast Cancer Spread

Metastasis occurs when breast cancer cells begin to grow in another body part.

It is hard to say exactly how quickly breast cancer can grow, including the timeframe, as the disease affects each person differently.

Cancer occurs due to mutations in human cells. Mutations do not follow normal, predictable patterns of cell division, so it is difficult to predict the progression.

Tumors appear when damaged cells replicate over and over to form a clump of abnormal cells. Breast cancer cells can break off and move through the lymph or blood vessels to other areas of the body.

If breast cancer cells begin to grow in another body part, this is called metastasis. Breast cancer is most likely to metastasize to the lymph nodes, lungs, and bones.

Regardless of the location of the new tumor, doctors still consider it to be breast cancer.

Breast cancer growth and its chances of spreading depend on the following:

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Survival Rates And Prognosis

The outlook for breast cancer is often described in terms of relative survival rates.

Relative survival rates are an estimate of the percentage of people who will survive their cancer for a given period of time after diagnosis. Survival among people with cancer is compared to survival among people of the same age and race who have not been diagnosed with cancer.

Five-year relative survival rates tend to be lower for triple-negative breast cancer than for other forms of breast cancer.

According to the American Cancer Society, the overall 5-year relative survival rate for TNBC is . However, an individuals outlook depends on many factors, including the stage of the cancer and the grade of the tumor.

Your healthcare professional will be able to give you a more precise outlook based on:

  • the stage of your TNBC
  • your age

Pathogenic Variants Identified By Panel Testing

Dr arun Triple Negative Breast cancer Presentation

From the clinical cohort, PVs in all 21 genes were detected in 14.4% of TNBC patients of any race or ethnicity, 14.0% of Caucasians, and 14.6% of African Americans . Of the 2148 TNBCC patients, 14.5% had PVs in 17 genes . PALB2 and BARD1 were the most commonly mutated non-BRCA1/2 genes in the clinical cohort and TNBCC study . Characteristics of TNBC patients with PVs are shown in and .

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Reducing Your Risk Of Triple

Its difficult to reduce your risk of triple-negative breast cancer because you cant control your age or your race. However, women who test positive for the BRCA1 or BRCA2 gene mutations may want to consider preventive mastectomy. It can reduce the risk of breast cancer in these women by about 97%. But it isnt an easy decision. There are many things to consider before moving forward with surgery. During genetic testing for breast cancer, you will explore the risks and benefits to help you decide if its right for you.

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What Is The Treatment For Triple

Chemotherapy.Chemotherapy is almost always called for, Sun says. Chemo can downstage tumors . While Sun says the chemotherapy for triple-negative breast cancer can be intense, she adds that regimen can be tailored to the individual and adjusted for older or frailer patients.

In those cases where we get complete response, we know we gave you the right medicine and your prognosis is good, Sun says.

Surgery can remove more of the tumor. Surgery for triple-negative breast cancer does not always have to be a mastectomy, Sun says. Effective chemotherapy done first opens up the possibility of less-invasive surgical options that are less of an ordeal for the patient. If the tumor is small enough after chemo, outpatient procedures or a lumpectomy may be possible.

Surgical samples of the cancerous tissues taken from surgery can provide more information on the cancer and how it is behaving so chemotherapy can be tailored accordingly.

Radiation therapy involves the use beams of radiation to destroy cancer cells, using various techniques to prevent damage to healthy surrounding tissue.

Medical treatments are being tested on triple-negative breast tumors in clinical trials.

Immunotherapy and PARP inhibitors are very exciting and theres lots of research going on, including here at Johns Hopkins, Sun says.

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Causes Of Triple Negative Breast Cancer

The risk factors for triple negative breast cancer are not clear. Some breast cancers depend on hormones to grow. These can be linked with risk factors to do with hormones and having children. But triple negative breast cancer does not seem to share these risk factors.

Most women with triple negative breast cancer have no strong history of breast cancer in their family . But some women with triple negative breast cancer have an altered BRCA1 gene. This will have been inherited from a parent.

An altered BRCA 1 gene can cause breast cancer to run in families. Most breast cancers caused by BRCA1 are triple negative.

If you have triple negative breast cancer, you may be offered genetic testing. This is even if you do not have a family history of breast cancer. Your cancer doctor or breast care nurse can explain more about this to you.

The tests are the same as for any type of breast cancer. You usually have a:

  • Mammogram

    A mammogram is an x-ray of the breast.

  • Ultrasound scan

    An ultrasound scan uses sound waves to produce a picture of the breast tissue and the lymph nodes in the armpit.

  • Breast biopsy

    When you have a breast biopsy, your cancer doctor or breast care nurse takes small samples of cells or tissue from your breast. The samples are looked at under a microscope to check for cancer cells. They also do other tests to find out if the cells have receptors for hormones, or for HER2.

See also

Factors Associated With More Rapid Spread

Research now showing different treatment options for triple negative breast cancers

Some types of breast cancer, as well as molecular subtypes, are more likely to spread and spread earlier than other types. Ductal carcinoma is more likely to spread than lobular carcinoma, among tumors that are the same size and stage.

While many breast cancers do not spread to lymph nodes until the tumor is at least 2 cm to 3 cm in diameter, some types may spread very early, even when a tumor is less than 1 cm in size.

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What Causes Triple Negative Breast Cancer

Many patients wonder what causes triple negative breast cancer. The breast cancer experts at Moffitt Cancer Center are often asked this question, but as of yet, there are no clear answers. As research continues, more is being learned about the causes of breast cancer in general, and triple negative breast cancer specifically.

Triple negative breast cancer differs from other types of breast cancer in that the cancer cells do not have receptors for estrogen, progesterone or HER-2/neu hormones. When these receptors are present and exposed to the corresponding hormones, they can stimulate the cancer to grow. But, this also means that triple negative breast cancer patients do not benefit from hormone-based treatments, such as tamoxifen and Herceptin, which are sometimes effective for treating hormone-receptor-positive cancers.

The current theories on what causes triple negative breast cancer and hormone-receptor-positive cancers also differ. For instance, some breast cancers that grow in response to hormone exposure have been linked to a womans childbearing characteristics, such as the age at which she gave birth for the first time. Triple negative breast cancer does not seem to share this link.

Some researchers believe that one possible cause of triple negative breast cancer is a faulty BRCA1 gene. Here are some of the factors that support this theory:



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