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.
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.
What Are Causes And Risk Factors For 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.
The following are causes and risk factors for any type of breast cancer, including triple-negative breast cancer:
- changes in the nipple, including inversion of the nipple and nipple discharge.
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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.
- 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.
Can You Predict Cancer Survival
Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor about how these numbers may apply to you, as he or she is familiar with your situation.
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Survival Rates By Stage
Breast cancer survival rates compare the number of women with breast cancer to the number of women in the overall population to estimate the amount of time women with breast cancer are likely to live after theyre diagnosed.
For example, if the survival rate for a stage of breast cancer during a 5-year period is 90 percent, it means that women diagnosed with that cancer are 90 percent as likely to survive for 5 years following their diagnosis as women who do not have the cancer.
As we mentioned earlier, survival rates are based on information from the SEER database, which the NCI maintains.
SEER does not group breast cancers by stages 0 through 4. Instead, it groups them by the following stages:
- localized: when the cancer has not spread outside of the breast
- regional: when its spread outside the breast to nearby structures or lymph nodes
- distant: when its spread to other parts of the body, such as the liver, lungs, or bones
It should be noted that theres a substantial racial disparity gap in survival rates between white women and Women of Color, especially for late-stage breast cancer diagnoses. The chart below, courtesy of the
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What Makes It Triple
Triple-negative refers to the fact that this type of breast cancer is not fueled by certain substances such as hormones or growth proteins in the body.
Estrogen and progesterone receptors are found in some types of breast cancer. Triple-negative breast cancer doesnt show hormone receptors on the cancer cells and most likely wont respond to breast cancer treatments using hormone blockers to slow the growth of cancer cells like many other types of breast cancer.
Another feature important for classifying breast cancer is the presence of the HER2 protein. Healthy cells have some HER2, but about 20% of breast cancer diagnoses have an excess of this protein, signaling the cells to grow and divide rapidly. Cancers that test positive for an excess of HER2 protein may be effectively treated using targeted therapies that disrupt the function and growth of HER2. Triple-negative cancer patients do not have a significant amount of HER2 protein fueling the cancer.
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Chemotherapy For Triple Negative Breast Cancer
TNBC has historically had limited treatment options when compared to other types of BC. The mainstay of treatment for TNBC remains cytotoxic chemotherapy, despite the emergence of new biologic and targeted agents. The therapeutic benefits of cytotoxic chemotherapy in TNBC are well established, with comprehensive data on the efficacy of chemotherapy in the neoadjuvant, adjuvant, and metastatic settings. Compared with hormone receptor-positive BC, the use of chemotherapy regimens in the neoadjuvant treatment of TNBC has a significantly higher pathological response rate and can considerably ameliorate the prognosis of TNBC patients . Nevertheless, TNBC carries an overall inferior prognosis despite its chemo-sensitivity . The use of neoadjuvant systemic treatment in the early stages is becoming the standard of care in TNBCs and is associated with higher pathological complete response rates as compared to other BC subtypes . Patients who achieve pCR with primary therapy have improved survival outcomes . As such, pCR is predictive of improved long-term outcomes for TNBC and is a reliable endpoint in clinical trials evaluating the efficacy of neoadjuvant chemotherapy.
What Are The Three Receptors In Breast Cancer
Triple-negative breast cancer: 5 things you should know. When doctors diagnose breast cancer, they look for three types of receptors estrogen receptor , progesterone receptor and human epidermal growth factor receptor 2 expressed in the breast cancer. These are what cause most breast cancers to grow.
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Characteristics Of The Sample
Of 50,856 subjects identified in this study, 9691 were TNBC and the remaining 40,589 were non-TNBC . The mean ages of the TNBC group and non-TNBC group were 54.21 and 53.62, respectively. TNBC patients accounted for 20.34%, 20.80%, 15.24%, and 15.65% of stage I, stage II, stage III and metastatic BC patients, respectively. The rate of positive lymph node status in non-TNBC group and TNBC group was 48.76% and 36.61%, respectively.
Of de novo metastatic breast cancer subjects, there was no significant difference in distributions of age and known lymph node status between mTNBC and metastatic non-TNBC . Subjects with mTNBC had higher CCI score than those with metastatic non-TNBC.
Table 1 Characteristics of the subjects with metastatic breast cancer.
Phase Iii Impassion 131
The IMpassion-131 study investigated if nab-paclitaxel could be replaced with paclitaxel in combination with atezolizumab in the first-line setting of advanced TNBC. Inclusion criteria were identical to the IMpassion130 trial, but the primary endpoint pertained to investigator-assessed PFS/OS tested first in the PD-L1 positive population. Patients were randomised in a 2:1 ratio to atezolizumab/paclitaxel vs placebo/paclitaxel . In the PD-L1 positive population, there was no significant improvement in the atezolizumab arm with a PFS of 6 mo compared to 5.7 in the placebo arm . There were also no significant differences in PFS in the overall population . In an interim OS analysis, there was no significant differences in OS in the PD-L1 population or the ITT population . The trend towards an improvement in OS was somewhat of a concern for investigators and the medical oncology community. Further analysis demonstrated that patients in both arm had an equivalent exposure to paclitaxel. The reasons for this trend however remain unclear. Speculation includes the potential immune mitigating effects of dexamethasone usage for paclitaxel treatment. This trial resulted in an FDA alert warning against the use of paclitaxel in combination with atezolizumab in TNBC. No new safety signals emerged.
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How Common Is Triple
About 10 to 20% of breast cancers are found to be triple-negative. However, triple-negative cancer cells are found more often in people under the age of 50. This is about 10 years younger than the average age of 60 or older for other types of breast cancer diagnoses. Triple-negative breast cancer is also found in higher percentages of Black and Hispanic patients and less often in Asian and non-Hispanic patients.
Another population that is more likely to be diagnosed with this type of breast cancer has an inherited mutation of the BRCA gene. About 70% of those with triple-negative breast cancer also test positive for having the BRCA mutation. You may qualify for genetic testing based on your family history. Learn more about genetic testing for breast cancer.
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.
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Clinical Features Of Metastatic Tnbc
Only 5% of patients with TNBC present with de novo metastatic disease. The majority of patients unfortunately relapse following treatment with curative intent. The biological features of TNBC result in a unique clinical phenotype. It is characterized by a propensity for visceral and brain metastases, absence of bone metastases and typically early relapse .
Data from a Canadian breast cancer cohort with 180 TNBC patients showed that these patients were much more likely to develop distant recurrence or death compared to other breast cancer subtypes. The risk of distant recurrence peaked at three years and declined rapidly thereafter. A large cohort study from MD Anderson Cancer Centre identified similar patterns of distant recurrence and death.
TNBC is most commonly associated with visceral metastases including lung, liver and brain. Jin et al identified 433 women with metastatic TNBC and found that 29% of them had 1 or greater brain metastases. Median survival from time of diagnosis of brain metastases in this study was just 7.3 mo highlighting the significant mortality associated with intracranial disease.
Symptoms Of Metastatic Breast Cancer
The symptoms of stage 4 breast cancer depend on the location of the cancer and where it has spread in your body.
- If breast cancer has spread to your bones, you may notice a sudden new bone pain. Breast cancer most commonly spreads to your ribs, spine, pelvis, or arm and leg bones.
- If it has spread to your brain, you may experience headaches, vision or speech changes, or memory problems.
- Breast cancer that has spread to your lungs or liver usually causes no symptoms.
The main treatments for stage 4 breast cancer are targeted drug therapies that destroy cancer cells wherever they are in your body.
These treatments may include:
- hormone therapy, which stops or slows the growth of tumors by preventing your body from producing hormones or interfering with the effect of hormones on breast cancer cells
- chemotherapy, where drugs given orally or through an IV travel through your bloodstream to fight cancer cells
- immunotherapy, which uses drugs that stimulate your immune system to destroy cancer cells
- a combination of these therapies
In some cases, surgery or radiation therapy may be used to treat stage 4 breast cancer.
The following are the common treatment options for different types of stage 4 breast cancer.
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What Is Triple Negative Breast Cancer
Triple negative breast cancer is a rare cancer that affects about 13 in 100,000 women each year. It represents about 15 % of all invasive breast cancers. Triple negative breast cancer is one of three types of breast cancer. It is called as triple negative because it doesnt have three markers associated with other types of breast cancer, which is important for prognosis and treatment. Its one of the more challenging breast cancers to treat. But researchers are making steady progress toward more effective treatments. Overall, 77% of women who have triple negative breast cancer are alive five years after diagnosis.
Compliance With Ethical Standards
The authors declare no conflicts of interest.
The study has been conducted in accordance with the Declaration of Helsinki. The Sahlgrenska University Hospital Ethical Review Board, Gothenburg, Sweden approved the study . The need for informed consent was waived under the approval of the Ethical Review Board due to the retrospective design.
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Epidermal Growth Factor Receptor
The epidermal growth factor receptor is reported in 89% of TNBC and is considered an attractive therapeutic target, particularly in BL2 subtype tumors . The expression of this gene results in primary tumorigenesis and metastasis. The EGFR inhibitor gefitinib lowers the proliferation of cancer cells and increases carboplatin and docetaxel cytotoxicity . Several EGFR inhibitors, such as lapatinib and erlotinib, are currently being tested against TNBC, in addition to cetuximab and panitumumab . The synergistic therapeutic approach of monoclonal antibodies and chemotherapeutics is considered to be more effective. This can be exemplified by the combined use of carboplatin and cetuximab, and cisplatin and cetuximab proved to be more efficacious in patients with advanced TNBC . Additionally, tri-inhibitor therapy, including carboplatin, gefitinib, and docetaxel, enhances TNBC cytotoxicity. Cannabidiol inhibits breast cancer metastasis by interfering with the epidermal growth factor pathway . The epidermal growth factor receptor signaling pathway is presented along with activator and inhibitor points of action, as shown in Figure 2.
FIGURE 3. Inhibition of poly polymerase in BRCA-1/2-associated and sporadic cancers .
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.
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Mammalian Target Of Rapamycin
The mTor pathway is responsible for poor prognosis due to the aggressive nature of the cancer and its good tissue invasion property . Errors in the mTOR pathway are strongly correlated with malignancy . The phosphorylation reactions of this pathway are also associated with proliferation, vascular endothelial growth factor, and angiogenesis, that enhance endothelial cell growth . Moreover, high expression of a protein kinase enzyme has been reported to be involved in tumor invasion and metastasis therefore, inhibiting the mTOR pathway can be an efficient anti-cancer strategy for several human malignancies . In general, inhibitors of the PI3K/AKT/mTOR network can be grouped as: 1) AKT blockers, 2) Pan-PI3K/mTOR blocker, 3) PI3K blocker, 4) Rapalogs , and 5) mTOR blocker . The mTor pathway and checkpoints where it can be blocked are presented in Figure 4.
FIGURE 4. The mTor pathway illustrating two distinct complexes . The pathway is stimulated by different growth factors. The mTORC2 activated Akt. Multiple cell functions are regulated by both mentioned complexes that are considered vital for cancer development. Also, in the figure different steps of the pathway that can be blocked by inhibitors are shown .
Survival Rate For Patients With Triple
Triple-negative breast cancer is considered aggressive, or fast-growing, but it is treatable. Survival depends on factors such as how advanced the cancer was at diagnosis, your overall health, and your response to treatment.
When assessing survival, researchers use a 5-year marker to make predictions about if cancer will reoccur.
According to the American Cancer Society, if any type of breast cancer is found to be stage 1, the 5-year survival rate is nearly 100%. Stage 2 breast cancer survival is about 93%, stage 3 is 72%, and metastasized or grade 4 breast cancer has about a 22% chance of survival. Keep in mind most triple-negative breast cancers are stage 3 when found.
Its important to note that the survival rates may be higher than this data suggests because new treatments are becoming available through clinical research.
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