Exposure To Chemicals And Drugs
Females who have been exposed to dreadful carcinogenic chemicals are at higher risk of breast cancer and epigenetic alterations and mutations. Exposure and duration of exposure contribute to an increased risk of breast cancer mutagenesis . Exposure of mammary glands to polychlorinated biphenyl and dichlorodiphenyltrichloroethane chemicals increases the risk of breast cancer . Furthermore, continuous exposure to organic solvents, insecticides, and oil mist increases the risk of breast cancer . Antibiotics, statins, antidepressants, and antihypertensive drugs can increase the risk of breast cancer. Similarly, NSAIDs that contain aspirin and ibuprofen are considered major risk factors for breast cancer .
Screening And Early Detection
Screening and early detection for TNBC are the same as for breast cancer in general. TNBC is only diagnosed after an initial breast cancer diagnosis is made.
Screening tests for breast cancer include:
Once breast cancer is diagnosed, tests will be done to detect different characteristics of the cancer cells, including what receptors they have and whether they make certain proteins.
TNBC is more aggressive and is typically diagnosed at a later stage than other kinds of breast cancer.
When Should I Go To The Emergency Room
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.
Immunosuppressive Immune Cells In The Tnbc Tumor Microenvironment
The tumor microenvironment involves the surrounding blood vessels, fibroblasts, immune cells, signaling molecules and the extracellular matrix around the tumor . Tumor Infiltrating Lymphocytes produce endogenous antitumor immune response for inhibiting tumor progression and improving free survival rate of TNBC patients . Tumor associated macrophages are important for immunosuppressive role by secreting inhibitory cytokines, regulatory T cells infiltration promotion, and reactive oxygen species reduction . Cancer-Associated Fibroblasts lower anti-tumor immunity, favor tumor cell proliferation and invasion and reshape the extracellular matrix . Tumor associated neutrophils aid in lysing tumor cells and induce antitumor function .
Our Breast Cancer Specialists
The breast cancer specialist team at Siteman comprises outstanding Washington University medical oncologists, radiation oncologists, surgeons, radiologists, geneticists and psychologists. The diverse expertise of our specialists is what allows them to create individualized treatment plans for all triple-negative breast cancer patients.
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Risk Factors For Triple
Doctors aren’t sure what makes you more likely to get triple-negative breast cancer. Not many women do — it only affects up to 20% of those who have breast cancer. You’re most at risk for triple-negative breast cancer if you:
- Are African-American or Latina
- Are under 40
- Have what your doctor will call a BRCA mutation , especially the gene BRCA1
Prognosis For Metastatic Breast Cancer
Metastatic breast cancer isnt the same for everyone who has it. According to the National Breast Cancer Foundation, your symptoms at stage 4 will depend on the degree to which the cancer has spread in your body.
Although metastatic breast cancer has no current cure, it can be treated. Getting the right treatment can increase both your quality of life and longevity.
Life expectancy for breast cancer is based on studies of many people with the condition. These statistics cant predict your personal outcome each persons outlook is different.
The following factors can affect your life expectancy with metastatic breast cancer:
- your age
What Are The Symptoms Of Metastatic Cancer
The symptoms produced by metastatic breast cancer vary depending on the location of the metastases.
For example, metastatic disease to the bone causes severe, progressive pain, and less commonly, pathological fracture, erythema over the affected bone and swelling.
Breast cancer cells that have spread to the brain cause persistent, progressively worsening headache, visual changes, seizures, nausea, vomiting, vertigo, behavioral and personality changes and increased intracranial pressure.
Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting.
Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest x-ray, and chest pain.
In addition, general, non-specific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss and poor appetite.
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.
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About Huntsman Cancer Institute At The University Of Utah
Huntsman Cancer Institute at the University of Utah is the official cancer center of Utah and the only National Cancer Institute -Designated Comprehensive Cancer Center in the Mountain West. The campus includes a state-of-the-art cancer specialty hospital, and two buildings dedicated to cancer research. HCI provides patient care, cancer screening, and education at community clinics and affiliate hospitals throughout the Mountain West. HCI is consistently recognized among the best cancer hospitals in the country by U.S. News and World Report. The regions first proton therapy center opened in 2021 and a major hospital expansion is underway. HCI is committed to creating a diverse and inclusive environment for staff, students, patients, and communities. Advancing cancer research discoveries and treatments to meet the needs of patients who live far away from a major medical center is a unique focus. More genes for inherited cancers have been discovered at HCI than at any other cancer center, including genes responsible for breast, ovarian, colon, head and neck cancers, and melanoma. HCI was founded by Jon M. and Karen Huntsman.
The Allograft Rejection Score Correlated Strongly With Cytolytic Activity And The Other Immune
The allograft rejection score was defined by the Gene set variation analysis algorithm as one of the immune-related Hallmark gene sets in molecular signatures database , similar to how we defined the other scores in our previous publications,,,,. To identify which cell types contribute to the allograft rejection score in the tumor microenvironment , the score was measured in a single-cell sequence cohort that has transcriptomes of tumor cells, stromal cells, T cells, B cells, and myeloid cells. A strong separation in the score was seen between the immune cells. T cells and myeloid cells had higher scores than tumor and stromal cells . Next, we investigated how well the score reflected the immune response in the TME of breast cancer. We found that the score was strongly correlated with the cytolytic activity score , which reflects immune cell killing =0.892 and 0.860, respectively, both p< 0.01). The score was also correlated with the other immune-related gene sets scores consistently in both METABRIC and GSE96058 cohorts, including complement, interferon – response, IFN- response, IL6/JAK/STAT3 signaling, and inflammatory response, but not with coagulation . These findings suggest that the allograft rejection score strongly reflects anti-cancer immunity in TME.
Fig. 1: Allograft rejection score strongly reflected anti-cancer immunity in breast cancer.
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Success Among Siteman Triple
In 2016, when Celina Campbell found a quarter-sized lump in her breast, she assumed it was just a swollen area due to a minor injury. However, breast cancer runs in Celinas family and her cousin had just received a TNBC diagnosis. Because of this, she began to suspect the lump could be cancer. After following up with a breast surgeon, it was indeed confirmed that Celina, too, had TNBC.
While triple-negative breast cancer treatment was very emotionally and physically draining, Celina remained determined to overcome her diagnosis. And, after eight sessions of chemotherapy, no more lump could be found. Now, six years later, Celina lives a full life and her cancer is considered fully cured.
Throughout her cancer journey, Celina received the most exceptional care and support from Sitemans breast cancer specialist team. Former Washington University medical oncologist William Popovic, MD, laid out a thorough and personalized treatment plan for Celina, putting her at ease with his warm demeanor and genuine concern. All of the staff dedicated themselves fully to Celinas journey, always working to help her understand her cancer and her treatment. The expertise, commitment and compassion of Washington University breast cancer specialists at Siteman allowed Celina to take charge of her life and to become an incredible inspiration to other TNBC patients.
What Are Breast Cancer Subtypes And Why Do They Matter
Your breast cancer subtype is one factor healthcare providers take into account when theyre deciding how to treat your cancer. Thats because not all cancer treatments are successful with all breast cancer subtypes.
Providers look at your cancer cells to identify subtypes. Specifically, they look for molecules on your cells surfaces. These molecules, called receptors, are built to order so only certain substances can climb on and start affecting what your cells do.
Breast cancer cells receptors are open to estrogen and progesterone. Understanding if your breast cancer cells have receptors and if theyre housing hormones helps providers determine how your breast cancer might spread and what treatment might be most effective.
The other type of breast cancer that has another receptor is called her-2 neu. This receptor makes the cells more active, but allows healthcare providers to treat the cancer with specific medicines that target her-2 proteins. If your breast cancer doesnt have her-2 neu and hormone receptors, its called triple negative.
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What Is The Staging Of Triple
Staging is the process of determining the extent of the cancer and its spread in the body. Together with the type of cancer, staging helps determine the appropriate therapy and predict the chances for survival.
To determine if the cancer has spread, medical professionals may use several different imaging techniques, including X-ray, CT scans, bone scans, and PET scans. Staging depends upon the size of a tumor and the extent to which it spread to lymph nodes or distant sites and organs in the body. Examination of lymph nodes removed at surgery and the results of ER, PR, and HER2 tests performed on the tumor tissue also help determine the stage of a tumor. Stage I is the lowest stage, while stage IV is the highest stage and refers to tumors that have metastasized, or spread to areas distant from the breast.
Most doctors specifically adjust breast cancer treatments to the type of cancer and the staging group.
Many women with breast cancer will require surgery. Broadly, the surgical therapies for breast cancer consist of breast-conserving surgery and mastectomy .
Types of chemotherapy include the following:
Other therapies for triple-negative breast cancer
How Common Is Triple
About 10 to 20% of breast cancers are found to be triple-negative. However, triple-negative cancer cells are found more often in people under the age of 50. This is about 10 years younger than the average age of 60 or older for other types of breast cancer diagnoses. Triple-negative breast cancer is also found in higher percentages of Black and Hispanic patients and less often in Asian and non-Hispanic patients.
Another population that is more likely to be diagnosed with this type of breast cancer has an inherited mutation of the BRCA gene. About 70% of those with triple-negative breast cancer also test positive for having the BRCA mutation. You may qualify for genetic testing based on your family history. Learn more about genetic testing for breast cancer.
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How Siteman Approaches Triple
According to the American Cancer Society , triple-negative breast cancer accounts for 10-15 percent of all breast cancers. It develops more quickly, is more likely to spread and is harder to treat than other breast cancers. Because its such an aggressive cancer, TNBC has a poorer prognosis than other invasive breast cancers.
T1a Tnbc Had Worse Prognosis Than T1a And T1b Her2+/hor Cancer
Both univariate and multivariate analyses proved worse BCSS and OS of T1a TNBC tumors than T1a HER2+/HoR tumors , whereas T1b TNBC patients revealed no survival difference compared with T1b HER2+/HoR tumors in terms of BCSS or OS . For T1c tumor, T1c TNBC had poorer survival than T1c HER2+/HoR .
Figure 2Table 3
Since T1a TNBC had worse prognosis than T1a HER2+/HoR and showed a trend with poorer survival than T1b TNBC, it raised the concern that whether T1a TNBC had the worst prognosis among small tumors of TNBC and HER2-rich subtypes. To prove this hypothesis, further comparison was performed between T1a TNBC and T1b HER2+/HoR. BCSS of T1a TNBC was significantly worse than that of T1b HER2+/HoR in both univariate and multivariate analyses. Multivariate analyses for OS also drew the similar conclusion that T1a TNBC associated with increasing mortality . Both BCSS and OS data supported the notion that T1a TNBC without chemotherapy has the worst prognosis among all the small tumor of TNBC and HER2-rich subtypes.
Figure 3Table 4vs.
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Survival Rates For Triple
The five-year survival rate for someone with localized triple-negative breast cancer, cancer that has not spread beyond the breast, is 91 percent . For cancer that has spread into nearby lymph nodes or nearby areas, the five-year survival rate is 65 percent. For cancer that has spread further into the body, such as into the bones, lungs or liver, survival is 11 percent.
Survival rates are averages determined by whats happened in the past. As research and cancer treatment evolve, the outlook may improve.
These statistics are recorded in the SEER database, which is maintained by the NCI, and do not differentiate between stages of cancer or take into account variables such as patient age and overall health.
Expert cancer care
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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Are There Any Statistics On Recurrence Rates Or Incidence Of Metastasis
As mentioned, it is very difficult to find statistics on metastatic breast cancer that has recurred after initial diagnosis. However, these cases represent a large proportion of Stage IV breast cancer cases and overall deaths.
Most of the statistical data on Stage IV or metastatic breast cancer is from those women presenting at diagnosis. According to the Metastatic Breast Cancer Network in 2012 new cases of Stage IV breast cancer were between 13,776 to 22,096.
The number of breast cancer recurrences at Stage IV is estimated to be between 20% and 30% of all breast cancer diagnoses.
Clinical Trials For Tnbc
Clinical trials are often used for triple-negative breast cancer treatment. Prior to taking part in a clinical trial, patients will first undergo standard treatments. However, if those treatments havent been successful, patients may choose to take part in a clinical trial in the hopes of a better outcome. If you are a TNBC patient interested in participating in a specific clinical trial, please speak with your physician about the trial.
The choice to participate in a clinical trial is highly personal, and one you should make after speaking with your provider about potential benefits and risks. While most health insurance plans cover clinical trials, make sure to first verify your coverage with your insurance carrier.
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Existing And Investigational Treatment Paradigm
From a chemotherapeutic perspective, TNBC is very sensitive, and treatments require extreme care. Common treatment involves the use of alkylating agents , anthracycline , anti-metabolite fluorouracil, and anti-microtubule agent . For early diagnosis of TNBC, neoadjuvant chemotherapy and subsequent surgery are applied. No standard chemotherapy has been described for the treatment of relapsed TNBC. Treating advanced TNBC includes the following drugs: gemcitabine and capecitabine , eribulin , and platinum . The conventional treatment options for TNBC are listed in Table 1.
TABLE 1. Conventional treatment option for TNBC.
TABLE 2. Different types of nano medicines under experimental and clinical testing for TNBC theranostics .