Statistics Dont Account For Late Recurrences
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.
Diagnosing Triple Negative Breast Cancer
In many women the cancer is found during breast screening. But symptoms such as a breast lump can be a sign of breast cancer. So it is important to get any symptoms checked by your doctor.
If you have symptoms and see your GP they refer you to a specialist breast clinic. At the breast clinic the doctor or breast care nurse takes your medical history and examines your breasts. They also feel for any swollen lymph nodes under your arms and at the base of your neck.
You have some of the following tests:
- a biopsy your doctor or nurse take a small sample of cells or tissue from your breast to look at under a microscope
Depending on your age and whether other family members have had breast cancer, your doctor might refer you for gene testing. This is to find out if there is a fault in the BRCA cancer gene.
Targeted Therapy For Her2
In about 1 in 5 women with breast cancer, the cancer cells have too much of a growth-promoting protein known as HER2 on their surface. These cancers, known as HER2-positive breastcancers, tend to grow and spread more aggressively. Different types of drugs have been developed that target the HER2 protein.
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Chemotherapy For Triple Negative Breast Cancer
Chemotherapy is often recommended for treating triple negative breast cancer. Unlike most other types of breast cancer, triple negative breast cancer does not respond to the presence of certain hormones, such as estrogen and progesterone, nor does it have an abnormally high level of HER2 receptors. Therefore, hormone therapy is largely ineffective for treatment purposes. Nevertheless, triple negative breast cancer often responds very well to chemotherapy.
Depending on when chemo is administered, its goals can vary. For instance, chemotherapy may be recommended prior to surgery to attempt to destroy rapidly dividing cancer cells. In this way, it may be possible to shrink tumors and make them easier to remove, which can increase the likelihood of a successful surgical outcome. Additionally, because it is not always possible for a surgeon to completely remove a patients cancer, chemotherapy may be recommended after surgery to target any remaining cancer cells and help prevent spread and recurrence. Alternatively, chemo can be used as a primary form of treatment to control the growth and ease the symptoms of large tumors that cannot be surgically removed.
Infused into a vein through an intravenous drip
Injected by needle into a vein or muscle
Taken by mouth in pill or capsule form
Swallowed in liquid form
Management Of Tnbc: Evidence So Far
Despite it being a very heterogeneous disease, the treatment of patients with early TNBC is still founded on the administration of anthracycline/taxane-based chemotherapy. In a meta-analysis including women with hormone receptor -negative breast cancer treated in trials of non-taxane-based chemotherapy versus none, adjuvant chemotherapy reduced the 10-year risk of recurrence and breast cancer mortality . In a retrospective analysis of patients enrolled into 3 randomized trials of anthracycline/taxane-based chemotherapy, dose-dense anthracycline/taxane-based chemotherapy lowered the rate of recurrence and death by more than 50% compared to low-dose anthracycline-based chemotherapy in HR-negative, node-positive breast cancer . A meta-analysis using data of 100,000 women showed a reduced breast cancer mortality in patients receiving anthracycline/taxane-based chemotherapy. Proportional risk reductions were little affected by HR status .
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Research Into Triple Negative Early Breast Cancer
Research has identified a number of different sub-types of triple negative breast cancer, providing opportunities for new treatments that target these sub-types to be developed.
Targeted treatments are currently being investigated using PARP inhibitors for BRCA related cancers, and PI3K/AKT inhibitors and immunotherapy drugs for other sub-types.
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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A Note About Statistics
Survival rates are statistics. As such, they tend to tell us how the average person will do with an average triple-negative breast cancer. But people and tumors arent 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 there is lag time. The treatment of triple-negative breast cancer is changing, and new drugs have been approved.
Chemotherapy For Early Tnbc
Early TNBC is treated with chemotherapy. People with TNBC tend to get more treatment benefit from chemotherapy than people with hormone receptor-positive breast cancers do .
Some people get chemotherapy before breast surgery. This is called neoadjuvant chemotherapy.
For people with TNBC who have cancer remaining in their breast after neoadjuvant chemotherapy, treatment with the chemotherapy drug capecitabine may lower the risk of recurrence and improve survival .
Learn more about chemotherapy.
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
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Treatment For Triple Negative Breast Cancer
The main treatments for triple negative breast cancer are surgery, chemotherapy and radiotherapy. The treatment you need depends on:
- where the cancer is
- the size of the cancer and whether it has spread
- how abnormal the cells look under the microscope
- your general health
You might have surgery to remove:
- an area of the breast
- the whole breast
When you have your surgery, the surgeon usually takes out some of the lymph nodes under your arm. They test these nodes to see if they contain cancer cells. The surgeon might check the lymph nodes closest to the breast using a procedure called sentinel lymph node biopsy. Testing the lymph nodes helps to find the stage of the cancer and decide on further treatment.
After breast conserving surgery you usually have radiotherapy to the rest of the breast tissue.
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Platinum Chemo Should Be Standard For Younger Patients With Tnbc
Adding carboplatin to standard neoadjuvant chemotherapy improves outcomes in patients with triple-negative breast cancer , according to research presented at the San Antonio Breast Cancer Symposium 2022.
Researchers observed improvements in event-free survival and overall survival with the addition of carboplatin, but these benefits were limited to patients who were 50 years of age or younger.
These results suggest that adding carboplatin to taxane-anthracycline neoadjuvant chemotherapy should be the standard treatment in patients with TNBC who are 50 years of age or younger, said study presenter Sudeep Gupta, MD, of Tata Memorial Centre in Mumbai, India. Dr Gupta and colleagues conducted this phase 3 trial to evaluate the efficacy and safety of adding carboplatin to standard sequential taxane-anthracycline neoadjuvant chemotherapy in patients with TNBC who had no evidence of metastatic disease.
The study included 717 patients. The median age was 46 years . Most patients were 50 years of age or younger , were pre- or peri-menopausal , had locally advanced disease , and had node-positive disease . The patients were randomly assigned to receive standard sequential taxane-anthracycline neoadjuvant chemotherapy alone or in combination with carboplatin .
In the younger cohort, the 5-year EFS rate was 74.2% in the carboplatin arm and 61.7% in the control arm . In the older cohort, the 5-year EFS rate was 62.0% in the carboplatin arm and 69.3% in the control arm .
Chemo For Triple Negative Breast Cancer What To Expect
Yesterday, my mum was diagnosed with Triple Negative breast cancer. She has one 22mm tumor and they dont think there is any lymph node involvement, but shes having a CT scan tomorrow to check whether the cancer is anywhere else.
They want her to start chemo in 2 weeks, for 3 months. We dont really have much more info than that at the moment but we will have a meeting on Wednesday about her treatment plan.
I’m a mess, I’m only 23 years old and my mothers only 47. They have said the treatment plan has an 80% chance of being successful which I know is good odds. But I’ve also read about the liklihood of recurrence with TNBC and that’s already freaking me out.
She has also said she wants me to be the primary caregiver. She wants me to move back home with her to support her whilst she has chemo. I really want to be there for her in every way imaginable but I don’t know if my mental health can withstand being basically her only carer – especially if she has a particularly bad reaction to chemo.
We dont really have any other family, and the family we do have are isolating because of covid, so I dont know how much they’ll be able to help either. Its just so scary, I have PTSD and I struggle to get myself dressed, fed, and sleeping at a regular time even before this we received this diagnosis, so I’m worried I wont be able to keep up with her care and will end up having a mental breakdown, and wont be any to help her at all.
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About 15% of all breast cancer cases are Triple Negative. It is considered the most aggressive and treatment-resistant, cancer often recurring soonest if treatment fails. Since traditional chemo treatments focus on and target hormone-positive cancers, they dont have much to offer in terms of TNBC. TNBC cells dont have receptors for estrogen, progesterone, and Her2/neu, so they have nothing to grab onto. Additionally, since it is a less-targeted treatment, it is even more toxic to the body. But this doesnt mean it is all gloom and doom.
Brca1/2 Mutations And Homologous Recombination Deficiency
DNA damage in cells, caused by extracellular agents or endogenous events, is repaired by various DNA repair mechanisms. Those are base excision repair , nucleotide excision repair, mismatch repair, and double-strand break repair that includes either homologous recombination during the S and G2 cell cycle phases and nonhomologous end joining. BRCA1/2 is directly involved in DNA homologous recombination repair and plays an essential role in genome stability. Mutations in BRCA1/2 or other homologous recombination defects result in growth defects and genetic instability. Germline BRCA1/2 mutations are present in approximately 10% to 20% of patients with TNBC, especially in those aged < 60years.- The presence of these mutations is associated with hereditary breast and ovarian cancer syndrome. Almost all the known BRCA1 mutations have gene expression patterns coincident with basal-like subtype. BRCA2 mutation is more associated with lobular histology. Testing for germline BRCA1/2 mutations is essential in patients with mTNBC to predict future cancer risk and guide therapeutic strategies.
Although drug combinations are often used to treat early breast cancer, advanced breast cancer more often is treated with single chemo drugs. Still, some combinations, such as paclitaxel plus gemcitabine, are commonly used to treat advanced breast cancer.
For cancers that are HER2-positive, one or more drugs that target HER2 may be used with chemo.
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Molecular Subtypes And Characteristics Of Triple
To avoid blindly developing therapeutic strategies, identifying the complex TNBC subtypes and molecular hallmarks is necessary given that these features are closely linked with clinical outcomes, for example, response to chemotherapy, the pattern of recurrence, and prognosis. Different approaches, including somatic DNA mutation, copy number aberrations, gene expression profiling, and immune metagene information, were applied to analyze TNBCs as a highly diverse group of cancers.
Additionally, molecular alterations were assessed to explore various potential targets for TNBC treatment. It is worth mentioning that a deficiency in homologous recombination, which is partly associated with the loss of breast cancer susceptibility gene function in BC, is correlated with a good response to cisplatin treatment . In an early phase II clinical trial, patients with BRCA-mutant TNBC showed an overall response rate of 80% with single cisplatin therapy . A deficiency in homologous recombination means failure to repair DNA double-strand breaks and damaged DNA replication forks. Therefore, these individuals are also sensitive to poly-adenosine diphosphate -ribose polymerase inhibitors , as PARP is the enzyme that responds to repair DNA single-strand breaks and maintain genome stability.
Why It Gets Accelerated Approval
The FDAs accelerated approval is granted for certain drugs that treat serious conditions and fill an unmet need. The manufacturer of the drug is still required to conduct additional trials and is expected to submit more findings by September next year. Upon those results, the drug could garner traditional approval.
When breast cancer cell growth isnt triggered by estrogen, progesterone, or human epidermal growth factor 2 , its known as triple-negative breast cancer. This type of breast cancer is considered aggressive with poor prognosis.
It doesnt respond to hormonal cancer treatments that have helped improve survival rates for people with other forms of the disease. However, it does respond to chemotherapy, but cancer cells can develop a resistance to chemotherapy agents. The treatment can also be very difficult on the patient as it kills off healthy cells along with cancer cells.
Triple-negative breast cancer is most likely to affect Hispanic and African-American women, along with people who have the BRCA1 gene mutation. It can develop in women in their 40s and 50s.
Approximately 15 percent of breast cancers are triple-negative, the National Breast Cancer Foundation reports.
About one-fifth of people with triple negative breast cancer have the PD-L1 protein, which is what atezolizumab targets.
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Subtype Of Triple Negative Breast Cancer Responds Better To Chemotherapy
Researchers at Yale Cancer Center have identified a new subtype of triple negative breast cancer that shows significantly improved response to chemotherapy. Patients with the newly defined subtype BRCA-deficient triple negative breast cancer had significantly higher survival rates with chemotherapy.
Triple negative breast cancer disproportionately affects young women of all races and women of African ancestry, contributing to health disparities. In an era when personalized cancer therapy has improved survival rates, patients with TNBC remain at considerably higher risk of relapse and death than patients with other types of breast cancer. This fact is due to the aggressive nature of TNBC and the lack of newer targeted therapies for the disease.
The researchers in the Yale-led study performed whole exome sequencing a technique for sequencing all the expressed genes in a genome on TNBC tumors. They used the technique to identify mutations in specific genes, or pathways, that might indicate response or resistance to the standard of care, which is anthracycline/taxane chemotherapy.
The research team found that TNBC tumors carrying mutations in the AR and FOXA1 pathways had a significantly higher response rate 94.1% compared to 16.6% in tumors without the mutations.
Additional Yale authors of the study include Tingting Jiang, Weiwei Shi, Vikram Wali, Charles Li, and Richard Lifton.
Different Drugs Same Target
Breast cancers that are HER2-positive tend to be aggressive, with the excess HER2 protein on tumor cells fueling the cancers growth. In the late 1990s, trastuzumab was among the first targeted cancer therapies to be approved by FDA, after trials showed it could improve survival in women with metastatic HER2-positive breast cancer.
Over time, other HER2-targeted therapies emerged, some with alternative mechanisms for disrupting HER2 activity in cancer cells. Drugs like trastuzumab and pertuzumab are monoclonal antibodies that bind to the HER2 protein above the cancer cells surface, preventing it from acting or enlisting the immune system to help destroy cells that produce it.
Tucatinib, on the other hand, is a member of a class of drugs known as tyrosine kinase inhibitors . These drugs work by binding to the part of the HER2 protein that is inside the cell and preventing it from sending signals that promote cell growth. Other HER2-targeted TKIs include neratinib and lapatinib .
Some TKIs have multiple targets. But, compared with other HER2-targeted drugs, tucatinib appears to be relatively selective for HER2that is, its less likely to bind to related proteins, explained Stanley Lipkowitz, M.D., Ph.D., chief of the Womens Malignancies Branch in NCIs Center for Cancer Research. That selectivity limits the risk of side effects seen with other HER2-targeted TKIs that inhibit other targets, Dr. Lipkowitz said.
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