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Where Does Triple Negative Breast Cancer Spread

What Is Triple Negative Breast Cancer

What is Triple-Negative Breast Cancer, and How is it Treated?

A diagnosis of triple negative breast cancer means that the three most common types of receptors known to fuel most breast cancer growthestrogen, progesterone, and the HER-2/neu gene are not present in the cancer tumor. This means that the breast cancer cells have tested negative for hormone epidermal growth factor receptor 2 , estrogen receptors , and progesterone receptors .

Since the tumor cells lack the necessary receptors, common treatments like hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective. Using chemotherapy to treat triple negative breast cancer is still an effective option. In fact, triple negative breast cancer may respond even better to chemotherapy in the earlier stages than many other forms of cancer.

Axillary Lymph Nodal Involvement And Tumor Size

Axillary lymph nodal involvement is an important factor to recognize the staging, prognosis, and treatment of progression-free survival and overall survival of breast cancer. The common methods for determine the lymph node involvement in breast cancer are sentinel node biopsy , clinical assessment, axillary dissection, and evaluation of imaging methods. The predictor of axillary lymph node metastasis in general should be easy reproducible, cost-effective, high accurate, and induces minimum side effects on patients. If lymph-node metastasis is present, there is high risk of metastasis while if there is no lymph-node involvement, a patient has a low risk of metastasis. In addition, the presence of more than four lymph-node metastasis is associated with very high risk of metastasis and generally predicts a poor prognosis .

Breast Cancers Survival Is Influenced By Tumor Grade

Grade identifies the size and shape of the malignant breast cancer cells. At the event the breast cancer cells look very different than normal breast tissue cells, and random in appearance, they can be called, that was badly differentiated and described as âhigh gradeâ. Higher level breast cancer cells tend to really have a poorer prognosis.

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Immunosurveillance Escape: Maintaining An Immunosuppressive Environment By Regulating Neuroinflammation

Tumor-associated macrophages are important components of the metastatic microenvironment. Metastasis-associated macrophages show TNBCBM site-dependent differences in their molecular profiles. Lymphotoxin was the most significantly upregulated cytokine in TNBC cells metastasized to the brain parenchyma compared with that in the dura mater and was suggested to be directly involved in the M2 polarization of brain parenchymal MAMs. This suggested that there may be a link between the site specificity of metastatic TNBC cells and the MAM activation state.73 BM is also modified by other CNS microenvironment-derived factors. The expression of gamma-aminobutyric acid transporters was increased in BMs derived from TNBC and HER2-positive breast cancer compared with that in matched primary tumor tissues and the BMs, particularly TNBCBMs, were able to proliferate by metabolizing GABA as a biosynthetic energy source, which was more prominent in TNBCBM.74

What Is The Survival Rate For Triple Negative Breast Cancer

Pairing Up Against Triple

Survival rates are a way to discuss the prognosis and outlook of a cancer diagnosis. The number most frequently mentioned is 5-year survival. Many patients live much longer, and some die earlier from causes other than breast cancer. With a constant change and improvement in therapies, these numbers also change. Current 5-year survival statistics are based on patients who were diagnosed at least 5 years ago and may have received different therapies than are available today.

Below are the statistics from the National Cancer Institute’s SEER database for survival of all patients with breast cancer, by tumor stage:

IV 22%

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Survival Rates For Triple

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 he or she is familiar with your situation.

Factors Associated With More Rapid Spread

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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Triple Negative Breast Cancer Overview

Triple-negative breast cancer is a cancer that that does not have any of the receptors that are commonly found in breast cancer. TNBC tests negative for estrogen receptors , progesterone receptors , and human epidermal growth factor receptor 2 or HER2 protein.

This makes it difficult to treat with hormone medication as many of the drugs used for breast cancer treatment target these receptors.

As a result, triple negative breast cancer more likely to grow and spread quicker than other forms of breast cancer.

It also can make treatment more difficult, leaving the patient to undergo chemotherapy or clinical trials.

According to the American cancer society about 10-15% of all breast cancers are triple-negative breast cancers. For researchers, there is intense interest in discovering new medications that can treat TNBC breast cancer.

Progesterone receptor-positive and estrogen receptor-positive breast cancers are the most common. Progesterone and estrogen are the two main sex hormones in women.

There are hormonal therapies available that can help treat and prevent recurrence for people who develop one of these types. In fact, many breast cancers are both estrogen- and progesterone-positive. If one type of hormone therapy does not work, another therapy often has a positive outcome.

TNBC is different from the more common types of breast cancer. It is harder to treat and much more aggressive.

How Quickly Breast Cancer Develops

Breast Cancer Sub-types – Triple Negative Breast Cancer

You may have heard remarks that cancer has been present for five years before it is diagnosed, and this may sometimes be true.

The actual time it takes for breast cancer to grow from a single cancer cell to a cancerous tumor is unknown, as estimates based on doubling time assume that this is constant throughout the duration of tumor growth.

If doubling time were constant, cancer with a doubling time of 200 days would take 20 years to develop into a detectable tumor, and a doubling time of 100 days would take 10 years to be evident on exam.

In contrast, a breast tumor with a doubling time of 20 days would take only 2 years to develop.

Since the majority of studies have found the average doubling time to be between 50 days and 200 days, it’s likely that most breast cancers that are diagnosed began at least 5 years earlier .

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What Is The Life Expectancy For Triple

In general, about91% of all women with triple-negative breast cancer are still alive 5 years after diagnosis. If the cancer has spread to the lymph nodes near the breast the 5 year relative survival rate is about 65%. If the cancer has spread to distant places, the 5 year relative survival rate is 11%.

Where Do These Numbers Come From

The American Cancer Society relies on information from the SEER* database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.

The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages . Instead, it groups cancers into localized, regional, and distant stages:

  • Localized: There is no sign that the cancer has spread outside of the breast.
  • Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
  • Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.

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Triple Negative Breast Cancer Genetics

One of the leading causes of triple-negative is a womans genetic makeup, specifically the BRCA1 and BRCA2 genes, which are genes that are supposed to produce tumor suppressant proteins in the body.

In the case of triple-negative breast cancer, 10% to 15% of Caucasians with triple-negative breast cancer have a BRCA1 gene mutation, while 35% of African Americans with triple-negative breast cancer have a BRCA1 gene mutation.

For a while the BRCA1 gene was the only gene known for increasing the risk of triple-negative breast cancer.

These genes, if defected can increase their risk of getting any type of breast cancer by 20% as well as elevating the chances that their breast cancer diagnosis be triple negative breast cancers .

Statistics Dont Account For Late Recurrences

Accepting My Triple Negative Breast Cancer Diagnosis

When comparing triple-negative breast cancer to positive tumors, its important to keep in mind late recurrences. Most statistics are presented as five-year survival rate, and in this setting, triple-negative breast cancer can look more ominous. But looking at longer periods of time, say 20 years following diagnosis, this may be different.

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Local Or Regional Treatments For Stage Iv Breast Cancer

Although systemic drugs are the main treatment for stage IV breast cancer, local and regional treatments such as surgery, radiation therapy, or regional chemotherapy are sometimes used as well. These can help treat breast cancer in a specific part of the body, but they are very unlikely to get rid of all of the cancer. These treatments are more likely to be used to help prevent or treat symptoms or complications from the cancer.

Radiation therapy and/or surgery may also be used in certain situations, such as:

  • When the breast tumor is causing an open wound in the breast
  • To treat a small number of metastases in a certain area, such as the brain
  • To help prevent bone fractures
  • When an area of cancer spread is pressing on the spinal cord
  • To treat a blood vessel blockage in the liver
  • To provide relief of pain or other symptoms

In some cases, regional chemo may be useful as well.

If your doctor recommends such local or regional treatments, it is important that you understand their goalwhether it is to try to cure the cancer or to prevent or treat symptoms.

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The Emerging Concept Of Triple Negative Breast Cancer

Breast cancers are commonly associated with a high incidence and a high mortality rate in the female population worldwide. However, at a microscopic and molecular level, breast cancer is not a homogeneous disease, thus being the focus of numerous ongoing studies. The molecular heterogeneity of the normal breast tissue has been previously documented and has outlined the different molecular profiles of epithelial and non-epithelial cells responsible for the existence of several molecular types of breast carcinomas, already characterized . Starting from the histopathological classification up to the molecular classification, breast cancer has been constantly redefined in order to ensure a better management of the patient. In 2012 Boyle et al. stated that the minimal characterization of breast cancer was a situation that had lasted for a century, until a quiet revolution has taken place so that in modern times breast cancer is characterized by its molecular and clinical heterogeneity .

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How Is Triple Negative Breast Cancer Diagnosed

The first step might be a mammogram to evaluate a suspicious mass or lump in your breast. Based on what they learn, healthcare providers might perform a biopsy to remove breast tissue. Then they examine the tissues cells to determine the cancer subtype. Identifying the cancer subtype is part of the staging process, which is when providers decide how to treat your cancer.

Sometimes providers use the following tests before treatment to check on your tumors size and whether it has spread, or after treatment to monitor response to treatment:

Whats The Difference Between Stage 0 And 3 Breast Cancer

Delaying Chemo Linked to Worse Outcomes for Triple-Negative Breast Cancer

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.

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Concluding Remarks On Current And Future Perspectives On Tnbc Metastasis Therapy

Due to their molecular heterogeneity, there are no drugs that can target the entire spectrum of TNBC tumors and each subtype is vulnerable to specific therapeutic approaches. Despite the lack of FDA-approved targeted therapies for TNBC to date, ongoing clinical trials are assessing the efficacy of single or combinatorial approaches that tackle different TNBC molecular alterations. Up to 20% of TNBC have been associated with germ-line mutations in BRCA1 . TNBC tumors with loss of function of BRCA1 or BRCA2 are sensitive to poly polymerase inhibitors and alkylating agents that induce DNA double-strand breaks . Olaparib has been the most successful PARP inhibitor against BRCA-mutated TNBC, inducing partial responses in 54% of patients when administered as a single agent and an overall response rate of 88% when combined with carboplatin . Anti-androgens as well as FGFR inhibitors have been tested in clinical trials against TNBCs that are androgen receptor-positive or harbor FGFR amplification, respectively . Gamma-secretase inhibitors that block the NOTCH pathway are currently in clinical trials for TNBC patients with upregulated NOTCH signaling . All together clinical trials have shown that each agent alone provides small or no benefit in TNBC patients suggesting that further effort is needed to discover novel targets of TNBC and to identify each patients molecular profile that will lead to a more individualized treatment.

Types Of Breast Cancer

There are several types of breast cancer, and any of them can metastasize. Most breast cancers start in the ducts or lobules and are called ductal carcinomas or lobular carcinomas:

  • Ductal carcinoma. These cancers start in the cells lining the milk ducts and make up the majority of breast cancers.
  • Lobular carcinoma. This is cancer that starts in the lobules, which are the small, tube-like structures that contain milk glands.

Less common types of breast cancer include:

  • Medullary

  • Metaplastic

  • Papillary

  • Inflammatory breast cancer is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers.

  • Pagets disease is a type of cancer that begins in the ducts of the nipple.

Breast cancer can develop in women and men. However, breast cancer in men is rare. Less than 1% of all breast cancers develop in men.

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Is Keytruda Right For You

Keytruda is FDA-approved to treat certain types of triple-negative breast cancer.

Triple-negative breast cancer is breast cancer that is:

  • estrogen-receptor-negative
  • progesterone-receptor-negative
  • HER2-negative

Triple-negative breast cancers are usually more aggressive, harder to treat, and more likely to come back than cancers that are hormone-receptor-positive or HER2-positive. Triple-negative breast cancers don’t usually respond to hormonal therapy medicines or the medicines that target the HER2 protein.

Keytruda may be an option for people with triple-negative breast cancer that is:

  • unresectable locally advanced breast cancer
  • metastatic breast cancer
  • early-stage breast cancer with a high risk of recurrence

Unresectable locally advanced breast cancer is breast cancer that has spread outside the breast to other tissues in the breast area. Unresectable means that it cant be removed with surgery.

Metastatic breast cancer is cancer that has spread to other parts of the body away from the breast, such as the bones or liver.

Keytruda also may be an option for people diagnosed with:

Signs And Symptoms Of Triple Negative Breast Cancer


Triple negative breast cancer have the same sign and symptoms as other common types of breast cancer. The most common symptom of breast cancer is a new lump or mass.

A painless, hard mass that has irregular edges is more likely to be cancer, but breast cancers can be tender, soft, or round. They can even be painful.

For this reason, its important to have any new breast mass, lump, or breast change checked by an experienced health care professional.

Following are some of the signs and symptoms of breast cancer:

  • A lump or a mass
  • Breast skin that is red, flaky, dry and thick
  • Changes in the skin of the breast
  • Discharge from the nipple
  • Pain in the breast or nipple
  • Lumps or masses felt in the armpit
  • Retracted nipple

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What To Expect When Taking Keytruda

Keytruda is given as a 30-minute infusion, every 3 or 6 weeks, depending on the dose given at each infusion. The Keytruda infusion is given before the chemotherapy infusion. If you are receiving Keytruda for metastatic or unresectable locally advanced triple-negative breast cancer, you may continue treatment with Keytruda and chemotherapy for up to 2 years, unless the cancer grows or you develop unacceptable side effects.

Women who are pregnant or planning to get pregnant should not be given Keytruda. Keytruda can cause embryo death and birth defects. Its important that you dont get pregnant while youre getting Keytruda you must use effective birth control.


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