Frequency And Characterisation Of Late Events
illustrates the cumulative probabilities of remaining free from event for RFI, RFS, and DRFS. The 10-year RFI was 97%, RFS 91%, and DRFS 92%. The 15-year RFI was 95%, RFS 83%, and DRFS 84%. Of the 873 patients, 22 had late recurrences. Sixteen of the recurrences were distant. Sites of distant metastases included the lungs/pleura , distant lymph nodes , bones , liver , central nervous system , pancreas , and distant skin . Six patients initially presented with local recurrence only, with 5 presenting with ipsilateral breast masses and the other with regional lymph node recurrence. Of the 22 patients who had recurrences, 16 died, with a median time to death after recurrence of 1.2 years . There were 57 deaths: 28.1% were attributed to breast cancer, 63.2% to other, and 8.8% to unknown causes in the absence of documented recurrence. show comparison of patient, tumour, and treatment characteristics between patients who had an event and those who did not for each of the three end points in this study.
Brca1 Inherited Gene Mutations And Tnbc
Most breast cancers related to a BRCA1 inherited gene mutation are both triple negative and basal-like .
TNBC may also be related to a BRCA2 inherited gene mutation .
The National Comprehensive Cancer Network recommends people diagnosed with TNBC at age 60 or younger get genetic testing .
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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
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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.
How Triple Negative Breast Cancer Is Diagnosed
Breast cancer is often diagnosed using imaging tests and a biopsy. Some of the most common diagnostic tools for breast cancer include:
- Mammograms Digital mammography and full-breast tomosynthesis may be used to take X-rays of the breast from several angles.
- Breast ultrasounds During a breast ultrasound, penetrating sound waves make computerized pictures of the inside of the breast. Ultrasounds provide a much clearer image of breast tissue than mammograms and can define whether a mass is solid or filled with fluid.
- Magnetic resonance imaging An MRI is not always necessary to diagnose breast cancer, especially if the breast ultrasound was conclusive. But it can be a helpful screening tool for those with a higher-than-average risk for breast cancer.
- Biopsies Fine-needle aspirations, core-needle biopsies, stereotactic biopsies and surgical biopsies can be used to confirm a breast cancer diagnosis. During this procedure, tissue or fluid is removed from the breast and then analyzed under a microscope.;;
If breast cancer is the confirmed diagnosis after imaging tests and a biopsy have been done, the breast cancer cells will be sent to a lab to be analyzed. If the cells do not have progesterone and estrogen hormone receptors or an excess amount of the HER2 protein, the resulting diagnosis is triple negative breast cancer.
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Triple Negative Breast Cancer Clinical Trial
Ongoing clinical trial tried to investigate effectiveness and safety of different possible treatment for future use and also has several clinical trials in the pipeline. The patient can also enroll their name in these trials to get novel therapies and also assist in research by providing the data to the research team. The different research aim is different, some are investigating new therapies to treat the patient, whereas some drugs may use in preventive therapy. Name registration for a clinical trial is the first step to enrolling name to the research3,4.
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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Research Into Triple Negative Breast Cancer
Researchers are working to find new treatments for triple negative breast cancer. Much of this research involves looking for molecules in the body that are involved with cancer growth, and formulating a drug that will disable how that molecule works.
Clinical trials;are in progress to determine whether these new drugs are better than the current standard treatment. If you would like more information on clinical trials, visit the clinical trials section of our website.
Variable And Outcome Definitions
The database was used to gather information regarding patient demographics , cancer stage , tumour characteristics , type of therapy , dosing and administration details of chemotherapy, and pathologic and clinical outcomes. Clinical outcomes included local recurrence, distant recurrence, breast cancer-related death, non-breast cancer-related death, and death from unspecified cause. These clinical end points were translated to the outcomes of interest on the basis of the STEEP criteria. Recurrence-free interval was measured from the date of diagnosis of primary cancer to the date of first invasive ipsilateral breast tumour recurrence, local or regional invasive recurrence, distant recurrence, or death documented because of breast cancer. Recurrence-free survival was measured from the date of diagnosis of primary cancer to the date of the first invasive ipsilateral breast tumour recurrence, local or regional invasive recurrence, distant recurrence, or death from any cause. Distant relapse-free survival was measured from the date of diagnosis of primary cancer to the date of first distant recurrence or death from any cause . Patients were censored at the date of their last follow-up for those who did not have an event.
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Analysis Of Public Microarray Data
The KaplanMeier Plotter tool was used to perform correlative analysis of publicly available gene expression datasets. The intrinsic subtype classification provided by the KaplanMeier Plotter tool was used to select cases for analysis . The following selections were applied to all analyses: only one JetSet best probe for each gene was used in the multigene classifier that calculates the mean expression of the selected probes, relapse-free survival was selected for the analysis, patients were censored at the follow-up threshold , biased arrays were excluded, and redundant samples were removed. The most significant cutpoint was used to split patients into two groups.
What Are Risk Factors For Breast Cancer Recurrence
Anyone with a breast cancer diagnosis can have a recurrence. Your risk of cancer recurrence depends on several factors:
- Age: Women who develop breast cancer before age 35 are more likely to get breast cancer again.
- Cancer stage: Cancer stage at the time of diagnosis correlates with the risk of the cancer being able to recur. Several factors determine cancer stage: tumor size, cancer grade and cancer spread to lymph nodes or other parts of the body. Cancer grade indicates how unusual cancer cells look in comparison to healthy cells.
- Cancer type: Aggressive cancers like inflammatory breast cancer and triple-negative breast cancer are harder to treat. Theyre more likely to come back and spread.
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Determining Risk Of Recurrence In Triple
A personalized prognosis for patients diagnosed with triple-negative breast cancer was the goal of a new study by Katherine Varley, PhD, researcher at Huntsman Cancer Institute and assistant professor of oncological sciences at the University of Utah.;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;
Twenty percent of women diagnosed with breast cancer in the United States will learn they have triple-negative breast cancer. That diagnosis means the three most common proteins known to fuel breast cancer growthestrogen receptor, progesterone receptor, and HER2are not present in the tumor. Those patients will not respond to any of the targeted therapies developed to treat breast cancer with those characteristics. After surgery, their only treatment option is chemotherapy. Targeted therapy allows healthy cells to survive, but chemotherapy can kill normal cells when eliminating the cancer cells.
Varley worked closely on the study with Rachel Stewart, DO, PhD, assistant professor of pathology and laboratory medicine at the University of Kentucky. They used specimens from patients treated at HCI. The tumor samples were taken more than five years ago, so the researchers could determine how each patient fared in the long term. The next step was developing a way to test for biomarkers of the immune response. The biomarker test was developed using formalin-fixed, paraffin-embedded tissues. This is important because it means this test can be run on tumor biopsy specimens that are routinely collected for breast cancer diagnosis. ;
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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Survival Rates And Prognosis
The outlook for breast cancer is often described in terms of relative survival rates.
Relative survival rates are an estimate of the percentage of people who will survive their cancer for a given period of time after diagnosis. Survival among people with cancer is compared to survival among people of the same age and race who have not been diagnosed with cancer.
Five-year relative survival rates tend to be lower for triple-negative breast cancer than for other forms of breast cancer.
According to the American Cancer Society, the overall 5-year relative survival rate for TNBC is 77 percent. However, an individuals outlook depends on many factors, including the stage of the cancer and the grade of the tumor.
Your healthcare professional will be able to give you a more precise outlook based on:
- the stage of your TNBC
- your age
What Causes Triple
Although there are known risk factors for the development of any kind of breast cancer, doctors do not understand the exact cause of breast cancer. Normal cells become cancer cells due to changes or mutations in the DNA. While people inherit some DNA changes, others acquire these DNA changes during a person’s life.
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What Is A 5
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 for at least 5 years after being diagnosed.
What Are The Types Of Breast Cancer Recurrence
If you develop cancer in the opposite, untreated breast , you receive a new breast cancer diagnosis. This isnt the same as breast cancer recurrence.
When breast cancer returns, it may be:
- Local: Cancer returns in the same breast or chest area as the original tumor.
- Regional: Cancer comes back near the original tumor, in lymph nodes in the armpit or collarbone area.
- Distant: Breast cancer spreads away from the original tumor to the lungs, bones, brain or other parts of the body. This is metastatic cancer, often referred to as stage 4 breast cancer.
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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.
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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What Tests And Exams Diagnose Triple
The diagnosis of triple-negative breast cancer requires a sampling of tissue from the breast, known as a breast biopsy. Medical professionals may perform the biopsy using imaging techniques, such as mammography or others, for guidance. If the biopsy shows cancer, they may perform other tests on the biopsy sample to determine the precise type of cancer. In particular, they commonly perform tests for expression of the estrogen receptor , progesterone receptor , and HER2 protein as a first step. If these tests are all negative, they classify the cancer as triple-negative breast cancer.
Immune Checkpoint Inhibitors For The Im Subtype
Pembrolizumab, a monoclonal anti PD-1, was tested in a phase Ib clinical trial in metastatic PD-L1-positive TNBC. It showed a preliminary ORR of 18.5% in heavily pretreated TNBC . The safety profile of the antibody was very acceptable.
Another anti-PD-L1 antibody, atezolizumab or MPDL3280A, has also shown promising activity in TNBC. In a phase I study with atezolizumab, 21 evaluable patients with metastatic PD-L1-positive TNBC achieved an ORR according to RECIST of 19% . 3 patients with PD-L1-positive TNBC experienced pseudo-progression, continued treatment, and finally demonstrated responses.
Preliminary results of a combination of atezolizumab plus nab-paclitaxel chemotherapy in metastatic TNBC have been reported , and a phase III trial with this combination as first-line therapy in untreated mTNBC has been opened. Multiple additional immune checkpoint receptors and their ligands are prime targets for blockade, such as CTLA-4 . The monoclonal antibody tremelimumab, which inhibits the CTLA-4 pathway, was evaluated in hormone-positive breast cancer and has shown certain activity .
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What Is The Prognosis For Triple Negative Breast Cancer
Triple negative breast cancer can be more aggressive and difficult to treat. ;Also, the cancer is more likely to spread and recur. ;The;stage;of breast cancer and the;grade of the tumor;will influence your prognosis. Research is being done currently to create drug therapies that are specific for triple negative breast cancer.
Interested in learning more? i3Health is hosting an upcoming webinar Metastatic Triple-Negative Breast Cancer: Applying Treatment Advances to Personalized Care. Learn more here.
Material on this page courtesy of Johns Hopkins Medicine
New Medications For Metastatic Breast Cancer
The immunotherapy drugs called checkpoint inhibitors have led to a significant improvement in survival rates for lung cancer and melanoma. In March of 2019 the first immunotherapy drug, Tecentriq was approved for triple-negative breast cancer that is metastatic . As noted above, there are at least a few people who have had excellent responses in clinical trials prior to approval.
PARP inhibitors are also a class of medications that may alter survival rates in the future, particularly among women who have hereditary breast cancer .
For bone metastases, bone-modifying drugs may be effective in treating both metastases, and may reduce the development of further metastases in bone.
Finally, for people who have only a single or a few metastases , treating these metastases locally may be an option. While studies are young, treating oligometastases may improve survival or even lead to long term survival for a minority of people.
In addition, for some people treated with immunotherapy, local radiation may sometimes improve the response of immunotherapy, something known as the abscopal effect. Since immunotherapy is such a recent addition to breast cancer, it’s not known how common this response may be or if it will be seen at all.
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