What Is Triple Negative Breast Cancer
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.
Trials For Advanced Triple Negative Breast Cancer
Trials are comparing different types of chemotherapy to see which are better at treating advanced disease. For example, researchers are waiting for the results of the Triple Negative Trial to find out whether it is better to use carboplatin or docetaxel.
Research is looking at using targeted cancer drugs alongside other treatments. For example, a trial is using a drug called atezolizumab in combination with chemotherapy. Some trials are testing a drug called pembrolizumab. Researchers think that these targeted drugs on their own might help to control the growth of the cancer.
National Institute for Health and Care Excellence , July 2018
Biology and management of patients with triple negative breast cancerP SharmaThe Oncologist. 2016, Volume 21, Issue 9
4th ESOESMO International Consensus Guidelines for Advanced Breast CancerF Cardoso and othersAnnals of Oncology,2018, Volume 29, pages 16341657
Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upF Cardoso and others
Compliance With Ethical Standards
The research work complied with the current laws of China and approved by the Institutional Review Board of Peking Union Medical College Hospital . The data released by the SEER database do not require patient informed consent because cancer is a reportable disease in every state of the United States and the procedures are in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Tnbc Chemotherapy Drugs And Efficacy Evaluation
Compared to other types of breast cancer, TNBC has limited treatment options, is prone to recurrence and metastasis, and has a poor prognosis. The main reason is that the expression of ER, PR, and HER2 are all negative, making specific endocrine therapies and targeted therapies ineffective. Therefore, chemotherapy has become the main approach for the treatment of TNBC. In recent years, a large body of literature has shown that the use of neoadjuvant chemotherapy regimens in the treatment of TNBC has a significantly higher pathological remission rate than for hormone receptor-positive breast cancer and can significantly improve the prognosis of TNBC patients. The national comprehensive cancer network guidelines recommend using combination regimens based on taxane, anthracycline, cyclophosphamide, cisplatin, and fluorouracil. At present, taxel/docetaxel + adriamycin + cyclophosphamide , docetaxel + cyclophosphamide , adriamycin + cyclophosphamide , cyclophosphamide + methotrexate + fluorouracil , cyclophosphamide + adriamycin + fluorouracil , and cyclophosphamide + epirubicin + fluorouracil + paclitaxel/docetaxel are the preferred adjuvant regimens for TNBC. Therefore, the selection of appropriate chemotherapy drugs and the optimization of chemotherapy regimens are important for ensuring good treatment outcome and prognosis of TNBC patients.
Treating Triple Negative Breast Cancer Adapted To Cancer Stage
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The earlier triple negative breast cancer is found, the easier and cheaper it is to treat.
GridHEALTH.id Alertness to disease breast cancer in general it becomes very important considering the research results The International Agency for Research on Cancer which issued the Global Cancer Incidence, Mortality and Prevalence 2020 or what we know as GLOBOCAN 2020 shows that new events breast cancer worldwide ranks first.
With around 2.3 million new cases and 680 thousand deaths, Indonesia ranks the most with new cases approaching 66,000 and a death rate of more than 22,000 in 2020.
Triple Negatif Breast Cancer or breast cancer Triple negative is known as a type of aggressive cancer that grows rapidly, because it is negative for estrogen, progesterone, and also HER2.
TNBC tends to have spread when it is found, and the chance of reappearing after being treated is higher than other types of TNBC breast cancer other.
TNBC causes about 10-20% of cases breast cancer in total and affects women under the age of 40 years.
According to a 2014 study, the incidence of TNBC is the second largest in Indonesia among types breast cancer others with a percentage of 25%.
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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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Evolutionary Paths Of Tnbc
Analyses of paired primary and metastatic TNBC samples are also needed to better understand the drivers of disease progression. Clonal frequencies vary significantly across TNBC at the time of diagnosis, suggesting their occurrence at different stages of tumorigenesis . There are limited sequencing data in metastatic triple-negative tumors, and much remains unknown about the differences in the molecular landscape of TNBC over its natural history. Multiclonal seeding from different cell populations in the primary tumor to the metastasis has been reported in two cases of basal-like TNBC, where, in addition, most putative driver mutations were shared, rather than acquired, between primary and metastatic lesions . Also, most TNBC primary tumors and metastases are polyclonal, with overlapping clones, suggesting that polyclonal metastasis is common in TNBC. Phylogenetic analysis has the potential to distinguish local recurrences from second primary tumors and to help determine the origin of a metastatic lesion in a patient with a history of independent primary tumors . Given the differences in management of primary and recurrent tumors, sequencing of longitudinal samples could affect treatment decisions.
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In Pursuit Of The Consensus Tnbc Subtypes
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.
A Note About Statistics
Survival rates are statistics, and as such tend to tell us how the “average” person will do with an “average” triple-negative breast cancer but people and tumors aren’t statistics. Some people will do better and some people will do worse.
Very importantly, statistics are usually several years old. In order to calculate five-year survival rates, a person would have to have been diagnosed at least five years prior. And still there is lag time. The treatment of triple-negative breast cancer is changing, and new drugs have been approved.
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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.
What Has Been The Standard Protocol For Treating Triple
The standard protocol to treat early-stage triple-negative breast cancer confined to the breast and axillary lymph nodes is chemotherapy and surgery. Often chemotherapy is administered before surgery. At present there are no further treatment options for early-stage triple-negative breast cancer beyond close follow-up care with regular physical exams and mammograms.
There are, however, innovative approaches currently under study, including the addition of targeted therapy to this chemotherapy backbone.
For advanced triple-negative breast cancer, the current standard approach is to treat with various chemotherapy regimens. The most recent breakthrough in the treatment of such tumors is the success story of PARP inhibitors. Short for poly polymerase, PARP is an enzyme that is required for cells to repair the DNA damage induced by any form of injury . Unfortunately, the cancer cells also use this enzyme to correct the damage induced by chemotherapy, making that treatment less effective. Now researchers have shown that by including a drug that inhibits the PARP enzyme along with chemotherapy, they can cause more damage to triple-negative breast cancers than when chemotherapy is delivered alone.
Several clinical trials are currently under way at various centers, using different PARP inhibitors with different chemotherapy in triple-negative and genetically inherited breast cancers.
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Sample Type And Sample Size Required
The minimum sample size required was calculated before data collection for the primary objective with the following assumptions: statistical significance level p< 0.05, targeted statistical power of 80%, eight prognostic factors , and minimum partial coefficient of determination considered clinically relevant R20.10. Under these assumptions, a sample size of 144 patients was finally required. Given the retrospective nature of the study, we expected that 15% of patients would have missing data on the primary outcome and at least one of the eight prognostic factors. Therefore, we decided to increase the number of enrolled patients to 170.
Targeted Therapy In Tnbcs
Different potential therapeutic options in TNBCs are summarized in Figure . Unlike the luminal types and the HER2 overexpressing type of breast carcinomas, TNBC lacks a specific targeted therapy. However, considering TNBCs heterogeneity, it is possible that BRCA1/2 mutations, along with AR may represent potential molecular targets in TNBCs treatment . Also, Pim-2, a serin/threonine kinase strongly involved in breast cancer metastasis, may become a therapeutic target in TNBCs . HJ-PI01, a Pim-2 inhibitor, seems to induce autophagic cell death and apoptosis thus decreasing malignant proliferation in TNBC cell lines . Shindikar et al. highlighted the anticancer properties of curcumin and resveratrol in TNBCs treatment, however, difficulties regarding their in vivo availability, distribution and kinetics along with a poor solubility, limits their routine use in patients . Chemotherapeutic agents such as nab-paclitaxel seems to be beneficial in the treatment of aggressive forms of breast cancer, such as TNBCs and HER2+, as well as in elderly and taxane-pretreated women .
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T1a Tnbc Had Comparable Survival With T1b Tnbc And T1a/t1b Tnbc Had Better Survival Than T1c Tnbc
There was no survival difference between T1a and T1b TNBC in terms of BCSS and OS . However, Kaplan-Meier curves showed a trend of worse prognosis of T1a TNBC than T1b TNBC, which was contradictory to the common sense that large tumor usually had poor prognosis .
Figure 1Table 2
T1c tumors was strongly associated with poor BCSS and OS , compared with T1b tumors .
Statistics Don’t Account For Late Recurrences
When comparing triple-negative breast cancer to positive tumors, it’s 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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Youre Not Too Young For Breast Cancer
Im surrounded by too many women in their 20s, 30s, and 40s who were denied early screening because they were deemed too young by their doctors to have breast cancer. This must change.
You are not too young to get breast cancer. Younger women tend to have more aggressive cancers. Check your breasts. And advocate for yourself ask for an ultrasound or MRI along with your mammogram if you have dense breasts.
Im getting my post chemo mammo and US today. #tnbc
Kerry K. Taylor May 27, 2020
Breast cancers in premenopausal women tend to be more aggressive and are often missed because young women are considered too healthy to get cancer. This can lead to a Stage 3, or a Stage 4 Metastatic Breast Cancer diagnosis.
My advice to every woman is to advocate strongly for yourself. Be bold and tell your doctor you want a mammogram or an ultrasound. Then tell them again. OR find another doctor who takes action. This is not a drill.
Putting off a breast exam because youre scared is normal. Not wanting to see a doctor because you found a lump or are experiencing a breast change is normal. Go anyway. Find the f-cker early. You have my permission. Now go.
My GP took my concerns seriously and I was monitored early. When a lump became palpable three weeks after an initial check, my case was escalated for an ultrasound with a core needle biopsy.
Id like to add my GP and surgeon to the list of people who saved my life.
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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Epigenetic Markers And Therapies In Tnbc
Epigenetic alterations, including changes in DNA methylation of gene promoter regions and posttranslational modification of histone proteins, are a recognized hallmark of cancer. Approximately 60% to 80% of basal-like and claudin-low breast cancers have aberrant DNA hypermethylation . Compared with luminal and HER2-positive cancers, TNBC exhibits extensive CpG methylation of the promoter regions of nine epigenetic biomarker genes . DNA hypermethylationdependent silencing of these genes is associated with worse RFS across all molecular subtypes and stages, compared with breast cancers unmethylated for these genes . A nonsignificant trend toward RFS disadvantage has also been described among basal-like and claudin-low tumors that have this 9-gene methylation signature . In addition, promoter hypomethylation of three breast cancer stem cellrelated genes , which strongly correlates with positive IHC staining and thus gene activation, has been shown to predict triple-negative status . Differences in histone modifications are also associated with differences in the expression of breast cancer genes across subtypes, separating luminal tumors, enriched with H3K27me3-modified genes, from nonluminal tumors , enriched with H3K9ac-regulated genes .
Treatment For Triple Negative Breast Cancer
Treatment for triple negative breast cancer usually involves surgery , radiotherapy if breast conserving surgery was performed, and chemotherapy. If you would like to read more about the main types of breast cancer surgery, visit the surgery section of this website.
As triple negative breast cancer is usually very responsive to chemotherapy, your medical oncologist will most likely develop a chemotherapy treatment plan for you. This will take into account your own individual needs and preferences.
Chemotherapy is usually given after breast cancer surgery. Sometimes it is given before surgery to shrink the tumour to allow for a smaller and easier operation. Some people may be offered chemotherapy before surgery this is called neoadjuvant chemotherapy.
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Tnbc Subtyping And Treatment Regimens
In 2011, Lehmann et al. performed gene expression profiling of tumor samples from 587 TNBC patients and divided TNBC into six subtypes: basal-like 1 , basal-like 2 , mesenchymal , mesenchymal stem-like , immunomodulatory , and luminal androgen receptor . They also performed gene profiling and compared existing TNBC breast cancer cell lines, classifying them into six different subtypes, thus providing an accurate cell model for clinical treatment of TNBC .
Table 1 Genomic TNBC subtypes and assignment of TNBC cell lines to subtypes