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Why Is Triple Negative Breast Cancer So Aggressive

What Are The Symptoms Of Triple Negative Breast Cancer

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

The symptoms of triple negative breast cancer are the same as any other type of breast cancer.

Symptoms can include:· A new lump in the breast, armpit area or around the collarbone.· A change in breast size or shape.· Changes to the nipple, such as sores or crusting, an ulcer or inverted nipple.· Clear or bloody nipple discharge.· Changes to the skin including redness, puckering or dimpling .· Breast tenderness or pain

You can learn more about the symptoms of breast cancer here.

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.

Do I Need Genetic Counseling And Testing

Your doctor may recommend that you see a genetic counselor. Thats someone who talks to you about any history of cancer in your family to find out if you have a higher risk for getting breast cancer. For example, people of Ashkenazi Jewish heritage have a higher risk of inherited genetic changes that may cause breast cancers, including triple-negative breast cancer. The counselor may recommend that you get a genetic test.

If you have a higher risk of getting breast cancer, your doctor may talk about ways to manage your risk. You may also have a higher risk of getting other cancers such as ovarian cancer, and your family may have a higher risk. Thats something you would talk with the genetic counselor about.

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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:


What Is The Treatment For Triple Negative Breast Cancer

Common drug may help battle aggressive breast cancer

Healthcare providers and researchers are making significant progress on TNBC treatments. Recent clinical trials are testing new combinations of drugs and new approaches to existing treatments. Some existing treatments are:

  • Chemotherapy: Providers might combine chemotherapy and surgery, with chemotherapy being used to shrink your tumor before surgery or after surgery to kill cancer cells throughout your body.
  • Surgery: This could be a lumpectomy to remove an individual lump, or a mastectomy to remove an entire breast. Providers then perform a sentinel node biopsy or axillary node surgery to look for signs your breast cancer has spread to your lymph nodes.
  • Radiation therapy: Post-surgery radiation therapy helps reduce the chances your cancer will return or recur.
  • Immunotherapy: This treatment stimulates your immune system to produce more cancer-fighting cells or help healthy cells identify and attack cancer cells. Immunotherapy can be added to chemotherapy to before surgery to shrink the tumor. You might also receive immunotherapy for about a year after your surgery and post-surgery radiation therapy.

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Molecular Subtypes Of Breast Cancer

In addition to ER, PR, and HER2, which are the key predictive biomarkers, advances in high-throughput technologies have shown breast cancer to be a molecularly, highly heterogeneous disease. The initial aim of classifying breast cancers had been for prognostication and prediction of response to chemotherapy, which with technological advances, has evolved into a broader aim of defining molecular classes by causal or driver alterations that determine patient outcome, disease aggressiveness, metastatic potential, or drug responsiveness.

Although expression subtypes have improved our understanding of molecular heterogeneity, the known expression subtypes do not represent the complete spectrum of the biological variation. Subtype characterization has been based on mRNA expression using microarrays in small sample sets, but its clinical utility is limited, given the lack of reproducibility and robustness, technological difficulties, and insufficient consideration to tumor heterogeneity. These limitations in clinical utility are discussed in greater detail elsewhere.

Molecular Subtypes of Triple-Negative Breast Cancers

Although precision in discovery of cancer drivers and propagating events is the key for clinical utility, discovery of more molecular subtypes based on less common driver events will be the result of the ongoing effort.

TV Ajithkumar, HM Hatcher, in, 2011

Triple Negativity And The Basal

In conclusion, the triple-negative group of breast cancer is not a homogeneous disease entity. However, a substantial fraction of these tumours belongs to the basal-like tumour type, which does form a homogeneous group. Thus, the overall poor prognosis of TNBC may be a result of this basal-like subgroup, and triple negativity may be seen more as a symptom than as a separate entity of breast cancer.

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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.
  • Dimpled skin.
  • 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.

Takeaways From A Triple Negative Breast Cancer Survivor

Chemotherapy Options for Triple Negative Breast Cancer

Though 1 in 8 women will be diagnosed with breast cancer in her lifetime, nothing about the experience feels normal. While every individual and every cancer are unique, we can all agree that breast cancer has a lasting impact on patients, survivors, and loved ones.

Shannon provides a candid glimpse into her journey with dense breast tissue and a triple negative breast cancer diagnosis. She faced breast cancer shortly after turning 40, with the support of her husband and community, while caring for her two young daughters. Shannon is the Head Drill Team Director at Highland Park High School in Dallas, TX. Only a couple months out of treatment, her memories are still fresh.

I thought I knew a little bit about breast cancer, so I didnt worry too much when I felt a small lump in the shower. Id had a mammogram within the past two years, and Id had benign issues prior to that. So I watched the lump for a few weeksa few weeks longer than I should have.

The doctor at my first visit told me that I had an 80% chance of the lump being absolutely nothing, but wed just check it out to be sure. The radiologist at my follow-up mammogram was concerned. But later that week, the doctor who biopsied me said the areas of concern looked benign to her. Lab results proved otherwise, and a day or two later, I got the dreaded phone call.

I want to share the following information not to frighten anyone, but to empower you with the knowledge I wish Id had:

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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.

Management Of Metastatic Triple

Triple-negative breast cancers do not express ER, PR, or overexpress the HER2 protein and are immunohistochemically characterized by staining for basal markers cytokeratin 5/6 and 17. Histologically they tend to be high grade with central necrosis.258 Microarray expression profiling analyses have demonstrated that breast cancers can be systematically categorized into biologically and clinically distinct subgroups. Triple-negative tumors are mostly but not exclusively categorized as basal-like breast cancers in the intrinsic PAM50 classification scheme introduced in 2000 by Perou and colleagues.259 They are so named because they arise from the outer layer of the breast duct, the myoepithelial cells.258 On a molecular level, they demonstrate a high frequency of p53 mutations, deficiencies in homologous recombination DNA repair, and elevated levels of genomic instability.206

At this time, there are no specific treatment guidelines for this patient population, and so most patients are treated on the basis of standard algorithms devised from clinical trials in which most women had luminal cancers. Triple-negative tumors tend to be initially more chemosensitive than their hormone-responsive counterparts.259 Unfortunately, however, the genetic instability seen in triple-negative tumors probably results in an increased potential for the subsequent development of chemoresistance, making their management even more challenging.262

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Study Suggests New Combination Approach For Treating Aggressive Subset Of Breast Cancer More Common In African American Women

Johns Hopkins Medicine
Different activity in two molecular networks could help explain why triple negative breast cancers tend to be more aggressive in African American women compared with white American women, a new study suggests.

Different activity in two molecular networks could help explain why triple negative breast cancers tend to be more aggressive in African American women compared with white American women, a new study led by Johns Hopkins Kimmel Cancer Center researchers suggests.

The findings, published online Dec. 20 in eLife, may explain the marked racial disparity in mortality for this subset of breast cancer and offer new strategies for treating this deadly disease.

“The incidence of breast cancer in African American women is lower than in white American women, but mortality is higher. Our work shows the molecular mechanisms that cause cancer cells to grow and spread faster in African American women,” says study leader Dipali Sharma, Ph.D., professor of oncology at the Johns Hopkins University School of Medicine and John Fetting Fund for Breast Cancer Prevention researcher.

“The triple negative breast cancer cells from African American women were more aggressive from the get-go,” says Sumit Siddharth, first author on the paper and postdoctoral fellow at Johns Hopkins Medicine.

“Eventually,” she says, “we may be able to close the survival gap between African American and white American women with triple negative breast cancers.”

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In Pursuit Of The Consensus Tnbc Subtypes

Bloodroot offers promise against triple

In the upcoming years, integrating different data sources will be key in identifying definitive TNBC subtypes that will help guide clinicians toward specific treatment recommendations for their patients. Integrative analyses comparing TNBC and non-TNBC patients from the TCGA cohort have been performed combining gene expression, DNAm, and somatic mutations, revealing differential signatures between these two types of BC . Thus, a similar approach combining even more layers of information may identify consensus TNBC subtypes. There is already one attempt to stratify TNBC patients using multiple data types, specifically using transcriptome , micro-RNA expression , and CNV . However, this study did not use metabolomics, proteomics, imaging, or histomolecular features, which have independently proven to be informative for subtyping TNBC.

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Who Is At Risk Of Developing Triple Negative Breast Cancer

Anyone can be diagnosed with triple negative breast cancer and should be aware of their own personal risk factors. You can use the online iPrevent tool to better understand your breast cancer risk and act on it.

There are a number of known risk factors for triple negative breast cancer including:

  • BRCA Mutations

    A BRCA1 gene mutation is associated with a higher risk of triple negative breast cancer. However, most triple negative breast cancers are not caused by a BRCA gene mutation. If you have a strong family history of breast cancer, you may wish to consider genetic testing. This is something to discuss with your doctor.

  • Being Pre-Menopausal

    While the average age of first being diagnosed with breast cancer in Australia is 61, triple negative breast cancer occurs more often in patients who are pre-menopausal or under 50 years of age. The cause of triple negative breast cancer in this young age group is not yet completely known. However, it could be due to breasts of younger women in their childbearing and breastfeeding years is of a different composition to the breast of an older women who has been menopausal for a long time.

  • African American and African Women

    Triple negative breast cancer is more likely to be diagnosed in African American and African women compared with white or Hispanic women. This is thought to be due to genes or mutations that pre-dispose this group of women, particularly pre-menopausal women, to triple negative breast cancer.

The Legacy Of Bc Subtyping Using Gene Expression Patterns

Long-non-coding RNAs were considered to classify TNBC tumors by Liu et al., given their role as regulators of gene expression. They combined mRNA and lncRNA expression profiles to construct the Fudan University classification system. Similar to the findings by Lehman et al. and Burstein et al., four subtypes were identified: IM, enriched in immune cell signaling pathways LAR, enriched in hormone-related pathways MES, whose main features were low levels of cell proliferation-related genes and enriched pathways associated with epithelial-mesenchymal transition and BLIS, showing upregulation of proliferative pathways and the downregulation of genes involved in the immune response. Again, patients with BLIS TNBC showed a worse overall prognosis. The authors compared these clusters with the TNBCtype-6 classification. They found that the IM groups were nearly identical in both studies, and LAR and BLIS partially covered Lehmanns LAR and BL1 groups, respectively. The authors also designed an IHC-based approach to classify TNBC patients . Quist et al. employed a four-gene signature to cluster TNBC tumors into six subtypes. The MC6 subtype, which comprised nearly 50% of TNBC samples, was associated with a higher sensitivity to platinum-based chemotherapy. Importantly, this correlation was further validated in TNBC cell lines .

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What Is The Prognosis For Triple

A good treatment result depends on several factors. Chemotherapy is what can really make a difference in the outcome. The size of the invasive part of the tumor, and the number of involved lymph nodes can also greatly influence your prognosis, Sun says, but adds that if the cancer has spread , the prognosis is less certain.

There is hope, even with this serious diagnosis, and staying optimistic is essential. It can be stressful and scary to go through chemo, but positive thinking can make a difference. You have to believe that its doing you good, and for most people, it does.

Breast Cancer Treatment at Johns Hopkins

The breast cancer program at Johns Hopkins is made up of a diverse group of nationally-recognized specialists in breast cancer research and treatment.


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