What Is Triple Negative Early Breast Cancer
Triple negative breast cancer is a type of breast cancer that does not have any of the three receptors commonly found on breast cancer cells the oestrogen, progesterone and HER2 receptors. Around 15% of early breast cancers are triple negative.
Triple negative breast cancer generally responds well to chemotherapy. Five years after diagnosis, people with triple negative breast cancer are no more likely to experience a recurrence of their breast cancer than people with other types of breast cancer. In the longer term , a recurrence is less likely with triple negative breast cancer.
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.
Role Of Platinum Agents
TNBC is often associated with a deficiency in BRCA-driven DNA repair mechanisms, leading to a higher sensibility to interstrand cross-linking agents damaging the DNA, such as platinum agents .
Contrary to data obtained in the metastatic setting, the carboplatin effect was independent of gBRCA status. Patients with gBRCAm had in general a higher pCR rate compared to wild type ones, but the increase in pCR with the addition of carboplatin was more prominent in the wild type cohort . One explanation of the different results could be the single versus combination therapy or the treatment setting.
Results of meta-analyses are consistent . Even though only a few small studies assessed the role of cisplatin , it seems to be as effective as carboplatin in increasing the pCR rate, but with a different safety profile . A head-to-head study of 4 cycles of weekly carboplatin or cisplatin and paclitaxel showed similar pCR rates and outcomes for the 2 compounds. No significant differences were seen in terms of AE .
Many new trials have incorporated carboplatin as part of the standard regimen. Its use is recommended irrespectively of the BRCA status.
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Combinations Of Immune Checkpoint Inhibitors
However, most patients with TNBC do not respond well to PD-1 or PD-L1 monotherapy therefore, inducing a favorable tumor immune microenvironment appears to be particularly important. Conventional chemotherapeutic agents, such as taxane, cisplatin, and cyclophosphamide, can enhance tumor antigen release, improve the tumor microenvironment, and add the possibility of an antitumor response . Biopsies before and after NAC showed that the immune microenvironment was altered from low TIL to high TIL, and patients with high TIL levels exhibited improved survival . For example, paclitaxel has pleiotropic immune-modulating effects because it helps mature dendritic cells shift the T-helper phenotype to promote the secretion of proinflammatory cytokines and enhance the activity of CD8+ T cells . An animal model has shown evidence that cisplatin markedly induces tumor regression and improves survival when combined with anti-PD-1 and anti-cytotoxic lymphocyte antigen 4 . These studies suggest that ICB combined with chemotherapy may achieve a synergistic or additive clinical effect.
In addition to the combination of PARPi and immunotherapy, a series of trials of immunotherapy in combination with other drugs have entered clinical studies . For example, alternative PD-1/PD-L1 ICB combined with tyrosinase inhibitors has entered phase III studies .
Table 4 Unpublished phase III trials of immunotherapy for TNBC
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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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.
Ethics Approval And Consent To Participate
The human study protocol was approved by Comité de Ãtica de la Investigación con Medicamentos , Hospital General Universitario Gregorio Marañón. The IiSGM Animal Care and Use Committee and Comunidad de Madrid approved all the PDX procedures . Procedures involving animal care complied with national and international laws and policies. The collection of samples was approved by the corresponding ethics committee . Patients provided written informed consent before any procedure.
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What About Hdc And Asct
One of the largest and best controlled clinical trials evaluating the use of high-dose chemotherapy and autologous stem cell transplant to treat patients with early stage breast cancer and more than 9 involved axillary lymph nodes continues to show survival benefit 20 years from receiving treatment. In fact HDC was associated with improved overall survival in the subgroup of women with triple-negative breast cancers: 52.9% of these patients were alive at 20 years compared with 37.5% of those in the conventional-dose chemotherapy.11
In the 1990s HDC and ASCT was increasingly used to treat breast cancer and other solid tumors based on its success in curing certain individuals with lymphoma, leukemia, and multiple myeloma. HDC continue to be the standard of care for many cancers but became out of favor as a treatment option for breast cancer due to conflicting study results and concerns about side effects.
The use of HDC for the treatment of breast cancer was based on the idea that breast cancer treatment could be improved if higher doses of chemotherapy could be administered and this has been borne out to be true. A standard treatment for high risk early stage breast cancer today is dose-dense chemotherapy which is widely used instead of HDC and ASCT and requires the use of blood cell growth boosters to ensure the chemotherapy can be safely administered in a timely manner.
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New Treatments Needed For Advanced Triple
Triple-negative breast cancer tends to be more aggressive, harder to treat, and more likely to recur than other forms of the disease, such as hormone receptorpositive or HER2-positive breast cancers.
Conventional chemotherapy drugs have not been effective against triple-negative breast cancer, and new treatment options are needed, said Jung-Min Lee, M.D., of the Womens Malignancies Branch in NCIs Center for Cancer Research.
In the KEYNOTE-355 trial, 847 patients with advanced triple-negative breast cancer were randomly assigned to receive chemotherapy plus placebo or chemotherapy plus pembrolizumab.
The study assessed the amount of time before the disease worsened and overall survival in all patients, in those with PD-L1 combined positive scores of 1 or more, and in those with combined positive scores of 10 or more. The trial was funded by Merck, the manufacturer of pembrolizumab.
The PD-L1 combined positive score is essentially a measure of the extent to which cells in a tumor produce PD-L1, the immune checkpoint protein that pembrolizumab targets. By blocking immune checkpoints, pembrolizumab and other immune checkpoint inhibitors unleash the immune system against cancer cells.
The incidence of treatment-related side effects, including serious side effects, was similar between the two groups of patients in the study.
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Home Remedies And Lifestyle
If you have had any of the standard therapies for TNBC, you may experience symptoms due to your cancer or as side effects of treatment.
There are a number of strategies you can use at home to alleviate your symptoms:
- Ice packs: Some women experience pain or swelling after breast cancer surgery or due to radiation. Ice packs, when used carefully, can help.
- Massage: You may have pain, aches, or soreness. If approved by your doctor, using a massaging device may be soothing.
- Exercise: Often, exercise can help reduce the swelling that follows a mastectomy or an axillary dissection. If swelling is a persistent problem for you, talk to your doctor about starting some regular exercises that you can do on your own. Often, keeping your arm lifted while it is resting is also recommended.
- Armband: For some women, a snug wrap around the hand or arm can help reduce the swelling that occurs after breast cancer surgery.
- Diet: You can experience a loss of appetite due or nausea to chemotherapy. And sometimes, TNBC can be so aggressive that it causes malnourishment and weight loss. You may need to work with a dietitian to make sure that you are getting a healthy balance of nutrients.
- Fluids: Drinking fluids such as water, ginger ale, or electrolyte drinks can help replenish you when mild dehydration is a problem . Ginger ale also counteracts mild nausea.
What Is The Relative Survival Rate Of Breast Cancer
A relative survival rate compares women with the same type and stage of breast cancer to women in the overall population. For example, if the 5-year relative survival rate for a specific stage of breast cancer is 90%, it means that women who have that cancer are, on average, about 90% as likely as women who dont have that cancer to live
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What To Do If Cancer Has Not Spread
If the cancer has not spread to distant sites, surgery is an option. Chemotherapy might be given first to shrink a large tumor followed by surgery. It might also be given after surgery to reduce the chances of the cancer coming back. Radiation might also be an option depending on certain features of the tumor.
Treatment Modalities Of Tnbc
Patients with TNBC do not benefit from hormonal or trastuzumab-based therapy because of the loss of target receptors such as ER, PGR, and HER-2. Hence, surgery and chemotherapy, individually or in combination, appear to be the only available modalities. However, some studies have identified certain receptors as targets for new therapeutic drugs.
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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.
Natural Remedies For Chemo Detoxing
New evidence suggests chemotherapy may be harmful to breast cancer patients. Thirty percent of breast cancer patients get chemotherapy. These medicines alter the immune system, and traditional physicians agree. Until now, no one knew how much. British research from the University of Leeds examined how chemotherapy impacted 88 breast cancer patients immune systems. Shocking outcomes
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How Is Tnbc Diagnosed
Imaging tests are usually the first tests done:
- Mammography, the most common screening tool for breast cancer, uses X-rays to take images of the breast and can uncover tumors that may be too small to feel.
- MRI uses a magnet, radio waves and a computer to make detailed images of the breast with a much greater resolution than a mammogram offers.
The next step is a biopsy to remove a sample of suspicious cells from the breast to analyze them. Techniques include:
The appropriate type of biopsy for you depends on factors such as the size and location of the tumor. You may also have a biopsy of your underarm lymph nodes at the same time to see if any cancer is there.
Breast cancer treatment: The care you need is one call away
Your multidisciplinary team will work with you to develop a personalized plan to treat your breast cancer in a way that fits your individual needs and goals.
Who Is Most At Risk For Triple
TNBC tends to be more common in women under 40 years old. Its also more common in African American women.
People who have a mutation in a gene called BRCA1 also have a higher TNBC risk. BRCA genes help repair DNA in our cells. If this gene is mutated, cells cant fix broken DNA. This can lead to breast cancer.
Whats more, up to 72% of women who have a BRCA1mutation will develop breast cancer by 70 to 80 years old.
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The Case For Chemotherapy For Tnbc
The benefits of cytotoxic chemotherapy for the treatment of TNBC are now well established with numerous studies demonstrating the effectiveness of chemotherapy in the neoadjuvant, adjuvant and metastatic settings. Many of the earlier studies were conducted before the discovery of HER2 and are therefore limited in their direct relevance to TNBC. Nevertheless, in retrospect the initial observations suggesting that estrogen receptor levels influence chemotherapy response provided an important foundation for modern trials to build upon. One of the earliest studies to suggest a differential benefit of chemotherapy based on ER status was a retrospective study of 70 patients with metastatic breast cancer. 6 Expression of ER in 25 patients correlated with a response rate of only 12% compared to a response rate of 75% among 45 patients without ER expression. However, a conflicting report published the same year suggested the response rate to chemotherapy in the metastatic setting was higher in the ER-rich subset compared to the ER-poor subset.7
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.
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Where Do These Numbers Come From
The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results Program 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.