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Triple Negative Breast Cancer Causes

How Common Is Triple

Risk factors for developing triple-negative breast cancer

Breast cancer continues to be a major health issue affecting women all over the world. Though the developed world has greatly reduced the impact of the cancer through screening, early diagnosis and appropriate treatments, breast cancer continues to contribute to a number of premature deaths in the developing and underdeveloped world.

Among the over 1 million cases of breast cancer diagnosed every year, it is estimated that around 170 000 are triple negative breast cancers. Around 75-85% of these are of the molecular subtype called basal-like. Basal-like cancers tend to be more aggressive.

The exact incidence of triple-negative breast cancer in India is not known however, mortality due to the cancer is higher in India as compared to the western world.

As for several cancers, the exact causes of triple-negative breast cancers are not known. Based on current information, women at high risk of developing triple-negative breast cancer include:

  • Younger women around 40 to 50 years of age
  • Women with mutation in the BRCA1 gene. The BRCA genes help to repair damaged DNA and maintain genomic stability. Mutation in the gene predisposes to breast cancer. A family history of breast cancer may be present in women with this mutated gene
  • African American and Hispanic women

What This Means For You

If youve been diagnosed with triple-negative breast cancer, this study offers some encouraging and interesting information. The results strongly suggest that triple-negative breast cancers are not all the same and that certain subtypes have better survival rates than hormone-receptor-positive breast cancer.

Determining the subtype of triple-negative breast cancer is not universally done. Still, many cancer centers do this type of testing. You may want to ask your doctor about this study, as well as whether subtype testing has been done as part of your pathology report and what it means for your prognosis and treatment.

Armed with the most complete information you can get, you and your doctor can make the best decisions for your unique situation.

What Does Triple Negative Mean In Terms Of Breast Cancer

Normal breast cells have receptors that respond to hormones such as estrogen and progesterone, which allows them to grow and regress in response to the hormone level. Hormone receptors may or may not be present in breast cancer. About two-thirds of breast cancers are positive and contain these receptors like normal breast cells do. These are less aggressive cancers that are less likely to need chemo and are often treated with hormone therapy and surgery. Radiation may or may not be needed.

HER2/neu , is a protein molecule that has a role in cell proliferation in normal cells. In some breast cancers, this protein is overly produced or positive. For HER2-positive tumors, there a specific medication that targets this protein.

Triple-negative breast cancers are not positive for estrogen receptors, progesterone receptors or HER2 protein. Since these targets are absent in triple-negative breast cancer, chemotherapy is needed, Sun says. Triple-negative breast cancer is often very sensitive to chemotherapy, which, despite the side effects, is an effective treatment that can save lives. Because this is an aggressive cancer, treatment is aggressive also. But there are several ways we can address it.

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How Do You Treat Triple

Due to the absence of hormonal receptors, triple-negative breast cancer does not respond to hormonal treatment. It also does not respond to treatments directed at HER-2 like trastuzumab.

Triple-negative breast cancer is treated with surgery, chemotherapy and /or radiation depending on the grade and the stage of the cancer. In fact, it may respond better to chemotherapy as compared to other cancers.

  • The chemotherapy used for triple-negative breast cancer is the same as that for other breast cancers and includes anthracyclines and taxanes. Drugs like capecitabine, gemcitabine, vinorelbine or albumin-bound paclitaxel may be administered to those who develop resistance to the initial treatment. Newer drugs like eribulin and ixabepilone can be used in patients who do not respond to the above treatment.
  • Given the high blood supply to the cancer, bevacizumab, a therapy directed against vascular endothelial growth factor may benefit patients with this type of breast cancer
  • Chemotherapy is sometimes administered before surgery on the cancer to reduce the size of the tumor and improve outcomes following surgery. This type of treatment is called neoadjuvant chemotherapy. Chemotherapy may also be given following the surgery.
  • Radiation therapy is also used in the treatment of triple-negative breast cancer.

Survival Rates For Triple

Dr arun Triple Negative Breast cancer Presentation

Triple-negative breast cancer is considered an aggressive cancer because it grows quickly, is more likely to have spread at the time its found, and is more likely to come back after treatment than other types of breast cancer. The outlook is generally not as good as it is for other types of breast cancer.

Survival rates can give you an idea of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed. They cant tell you how long you will live, but they may help give you a better understanding of how likely it is that your treatment will be successful.

Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor about how these numbers may apply to you, as they are familiar with your situation.

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What Is The Success Rate Of Treating Triple

The most prevalent kind of breast cancer in the United Arab Emirates is hormone-positive HER2-positive, hormone-positive HER2-negative, hormone-negative HER2-positive, and hormone-negative HER2-negative.

Locally advanced TNBC was discovered in a 35-year-old woman with Leukocyte adhesion deficiency. This patient had a combination of chemotherapy and immunotherapy as neoadjuvant treatment . After surgery, we discovered what we refer to as a complete pathologic response, which means we could not detect any trace of her cancer. This is the best possible outcome for a patient. In the past, we were unable to observe such excellent outcomes as frequently as we do now, but this has changed due to more advanced treatments.

Interfering With An Addiction

So the researchers tested a drug, THZ1, which targets a protein called CDK7, in a series of cell line and animal models of triple-negative breast cancer. CDK7 is a member of a family of enzymes known as cyclin-dependent kinases that help to control transcription.

In experiments on cell lines, THZ1 suppressed the proliferation of triple-negative breast cancer cells but had no effect on the proliferation of breast cancer cells that express hormone receptors, even though THZ1 blocked CDK7 activity in both cell lines. This finding indicates that the triple-negative cells appear to be far more dependent on the activity of CDK7 than the hormone receptor-positive cells, the researchers wrote.

The drug also shrank tumors in several mouse models of triple-negative breast cancer, including tumors derived from tumor fragments from two patients with metastatic disease whose cancers had progressed after multiple lines of treatment.

Further studies in cell lines using gene-editing technologies to block CDK7 activity, including the CRISPR/Cas-9 system, provided additional confirmation that triple-negative cancer cells were highly dependent onor addicted tothe gene cluster regulated by CDK7. However, the triple-negative cells were not addicted to genes regulated by other members of the CDK family, Dr. Zhao and her colleagues reported.

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Intake Of Processed Food/diet

According to the WHO, processed foods, such as meat, are confirmed group-1 carcinogen for gastrointestinal cancer and breast malignancy . The excessive use of saturated fats is also considered a carcinogen. The obesity-causing ultra-processed diet plans that are enriched in elements such as sugar, sodium, and fats are thought to be carcinogenic and increase the risk by 11% . Diets that are rich in green vegetables, fresh fruits, protein-enriched grains, and legumes are anti-carcinogenic and therefore reduce the risk of breast cancer . Similarly, diets rich in phyto-estrogen, folate elements, saturated fibers, n-3 PUFA, and vitamin D are regarded as anti-cancer agents . Hence, a low dose consumption of saturated fat and n-6 PUFA has been proposed . The antioxidants found in green tea have also shown anti-carcinogenic properties . Curcuminoids and sulforaphane derived from turmeric are thought to be anti-carcinogens .

Which Is The Most Serious Type Of Breast Cancer

Triple Negative Breast Cancer: What You Need to Know

TNBC is regarded as the most severe kind of breast cancer, although it is crucial to note that, due to recent improvements in therapy, TNBC is now easier to treat. TNBCs exhibit rapid growth and are more likely to be discovered clinically instead of through mammography than ER-positive tumors or tumors diagnosed between mammograms.

However, intrinsic variability in breast tissue density among women diagnosed with TNBC could account for these variations in presentation. The most prevalent form of TNBC is infiltrating ductal carcinoma, while medullary carcinoma, a rare subtype, is typically triple-negative. TNBCs may display geographic necrosis, an expanding invasion boundary, and a lymphocytic stromal reaction. Histopathologically, a unique subtype of TNBCs is identified as metaplastic. This is, nevertheless, a broad collection of cancer forms ranging from squamous to stromal.

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Stages Of Breast Cancer

The stage of breast cancer is based on the size and location of the tumor, as well as whether the cancer has spread beyond the part of the breast in which it originated. To determine the stage of breast cancer, healthcare professionals use a scale of stage 0 to stage 4.

Stage 0 breast cancers are isolated in one part of the breast, such as a duct or lobule, and show no sign of spreading into other tissue.

Stage 1 is typically localized, although further local growth or spread may cause the cancer to move into stage 2.

In stage 3, the cancer may be larger and has affected the lymph system. Stage 4 cancer has spread beyond the breast and nearby lymph nodes, and into other organs and tissues of the body.

In addition to stages, breast cancers are given grades based on the size, shape, and activity of the cells in the tumor. A higher-grade cancer means a greater percentage of cells look and act abnormal, or they no longer resemble normal, healthy cells.

On a scale of 1 to 3, with 3 being the most serious, TNBC is often labeled grade 3.

American Cancer Society , the symptoms of TNBC can be the same as those for other types of breast cancer. ACS recommends regular screenings such as mammograms to detect breast cancer before symptoms appear, the time when treatment is most effective.

Other signs of breast cancer include:

Any of these signs can be caused by other conditions. But it is always good to have them checked out by your healthcare professional.

What Are Symptoms Of Triple Negative Breast Cancer

TNBC symptoms are the same as other common breast cancers. And many breast cancer symptoms are similar to other less serious conditions. That means having certain symptom doesnt mean you have breast cancer. Possible breast cancer symptoms include:

  • A new lump or mass.
  • Swelling in all or part of a breast.
  • Nipple retraction, when your nipple turns inward.
  • Nipple or breast skin thats dry, flaking, thickened or red.
  • Nipple discharge that is not breast milk.
  • Swollen lymph nodes. This symptom happens when breast cancer spreads to the lymph nodes under your arm or near your collarbone.

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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:

When Should I Go To The Emergency Room

Dr arun Triple Negative Breast cancer Presentation

You might also have unusually strong side effects from your cancer treatment. While your healthcare provider likely gave you medication to help control your side effects, you should go to the emergency room if your side effects continue despite medication.

Many cancer treatments affect your immune system, increasing the chance you will develop infections. Symptoms that might require an emergency room visit during treatment are:

  • Fever of 100.5 and above.
  • Persistent nausea and vomiting.

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Is Breast Cancer Now Funding Research Into Triple Negative Breast Cancer

We have a dedicated Research Unit at Kings College London which is the only research unit in the UK focusing solely on understanding triple negative breast cancer and finding better ways to treat it.

Under the leadership of Professor Andrew Tutt, there are currently 29 researchers based at the unit, including Professor Ng and his team who study the role of immune cells in triple negative breast cancer. They are using imaging techniques to look at how immune cells enter the tumour environment and how this contributes to the growth and spread of triple negative breast cancer.

We also fund triple negative research elsewhere in the UK. For example, Professor Claire Lewis at the University of Sheffield is testing whether targeting two molecules called CXCR4 and VEGFA could prevent triple negative breast cancers from spreading around the body.

Dr Walid Khaled at the University of Cambridge is trying to understand how a protein called BCL11A, present in large amounts in triple negative breast cancer cells, is interacting with other proteins in these cells. He hopes that we may be able to kill triple negative breast cancer cells by using treatments to target these interactions.

Although this research may take some time to reach patients, its hoped these projects could lead to new treatment options for people with triple negative breast cancer.

How Soon Does Triple

It is not possible to predict if or when breast cancer will recur. This is even true for triple-negative breast cancer. However, the likelihood of a recurrence is generally higher in comparison to other breast cancers. The highest risk for recurrence is in the first few years after treatment. Some research suggests the three-year period after treatment is the critical time for recurrence. Once women reach year five after treatment, the risk of cancer coming back is the same as other forms of breast cancer.

Triple-negative breast cancer survival rate seems to follow a similar pattern. The 5-year survival rate is lower for women with triple-negative breast cancer compared to other forms. This rate looks at women who had treatment at least five years ago to see how many are still alive. One study found the five-year survival rate is 77% for triple-negative breast cancer and 93% for others. However, another study found the risk of dying decreased after five years post-treatment.

Keep in mind that all of these numbers are estimates. They are general guidelines for triple-negative breast cancer life expectancy. There are many things that contribute to your individual prognosis. The cancer stage and grade are two important ones. But there are others, including your age, your overall health, and the tumors response to chemo. Your doctor is the best resource for information about your outlook. He or she can help you understand how these factors apply to you.

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Targeting Tumor Microenvironment For Tnbc Therapy

The development of TNBC has strong association with the physiological state of TME. TNBC has been characterized with unique TME and is different from other subtypes . TME has strong association with induction of angiogenesis, proliferation, apoptosis inhibition, suppression of immune system and resistance to drugs . The exosomes function as promising nanovesicles that directs TME orchestration by communicating cells within TME milieu . The different components of TME particularly the soluble factors, transformed extracellular matrix, immune suppressive cells, re-programmed fibroblasts and epigenetic modifications altogether helps in TNBC progression and metastasis . Hence, TME is regarded as a good therapeutic target. The different TME targets for therapeutic intervention is schematically presented in Figure 5.

FIGURE 5. Different TME targets for therapeutic intervention.

Mammalian Target Of Rapamycin

The breakthrough research giving hope to patients with triple negative breast cancer | 7NEWS

The mTor pathway is responsible for poor prognosis due to the aggressive nature of the cancer and its good tissue invasion property . Errors in the mTOR pathway are strongly correlated with malignancy . The phosphorylation reactions of this pathway are also associated with proliferation, vascular endothelial growth factor, and angiogenesis, that enhance endothelial cell growth . Moreover, high expression of a protein kinase enzyme has been reported to be involved in tumor invasion and metastasis therefore, inhibiting the mTOR pathway can be an efficient anti-cancer strategy for several human malignancies . In general, inhibitors of the PI3K/AKT/mTOR network can be grouped as: 1) AKT blockers, 2) Pan-PI3K/mTOR blocker, 3) PI3K blocker, 4) Rapalogs , and 5) mTOR blocker . The mTor pathway and checkpoints where it can be blocked are presented in Figure 4.

FIGURE 4. The mTor pathway illustrating two distinct complexes . The pathway is stimulated by different growth factors. The mTORC2 activated Akt. Multiple cell functions are regulated by both mentioned complexes that are considered vital for cancer development. Also, in the figure different steps of the pathway that can be blocked by inhibitors are shown .

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