Survival Analysis Of Core Genes In Breast Cancer
UALCAN is a comprehensive web resource for analyzing cancer data , and GEPIA is an online tool for gene expression profiling interactive analysis as well . They can both provide graphs and plots depicting gene expression and patient survival information based on gene expression. KM is an online survival analysis tool to rapidly assess the effect of certain genes on cancer prognosis using microarray data . In our study, we first searched all the hub genes on the UALCAN website to identify the ones with poor survival. Then, we used GEPIA to rerecognize whether these core genes have different expressions between breast cancer and normal breast tissues. After that, we used the KM plotter to identify their OS and RFS among breast cancer patients.
Many Factors Can Affect Your Prognosis
Some of the factors that affect prognosis include:
- The type of cancer and where it is in your body
- The stage of the cancer, which refers to the size of the cancer and if it has spread to other parts of your body
- The cancers grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about how quickly the cancer is likely to grow and spread.
- Certain traits of the cancer cells
- Your age and how healthy you were before cancer
- How you respond to treatment
Two Mutually Exclusive Phenotypes In Breast Cancer
Through unsupervised clustering of GSVA enrichment scores, we identified two mutually exclusive gene signatures in breast cancer, one associated with proliferation and embryonic stem cell-like phenotype and and the other with EMT and mammary stem cell phenotype.
A;proliferative phenotype was dominating Cluster C , the same was observed when gene set scores were calculated for each METABRIC sample . In Cluster B, the average gene set scores were either high for EMT or proliferation-related signatures . At the sample level in the METABRIC, we observed a similar pattern with samples having the one or the other state activated . Cluster A showed low scores for both the EMT and proliferative states .
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Coping With A Breast Cancer Recurrence
Finding out that your cancer has come back can cause a mix of emotions. You might feel shocked, angry or frightened.
Its important that you have a chance to ask questions. Your cancer specialist can give you information thats tailored to your individual situation. Your breast care nurse can also be a helpful source of information and support.
Ongoing treatment and an uncertain prognosis can cause you to feel worried and anxious about your future. Theres no easy way to deal with this uncertainty but you might want to get in touch with other people who are going through something similar.
You can exchange tips on coping with uncertainty and side effects of treatment, ask questions, share experiences and talk through concerns on our online Forum.
You can also call our free Helpline on 0808 800 6000 for information and support, and to find out about Breast Cancer Nows services.
Statistical Survival Multivariable Cox Regression Analysis
All analyses were performed in the R version 3.3.2. Unless otherwise stated, results were considered statistically significant, if p value < 0.05. KaplanMeier estimator and log-rank tests were performed using the functions Surv, survfit, and survdiff . Multivariable Cox regression analyses were used to test the independent prognostic value of the immune clusters using the R package survival and the coxph function. MannWhitney U or KruskalWallis tests were used to assess statistical significance within boxplots.
In the box-and-whisker plots, the line within each box represents the median. Upper and lower edges of each box represent 75th and 25th percentile, respectively. The whiskers represent the lowest datum still within of the lower quartile and the highest datum still within of the upper quartile.
To identify differentially expressed genes between clusters, we used a t test followed by Bonferroni correction of the p value. A strict corrected p value was used to identify differentially expressed genes.
NRI and IDI were calculated using the survIDINRI v1.11 R package. To assess the 95% CI and p values for the IDI and NRI, a standard bootstrap method was used with resampling performed 500 times. NRI and IDI were assessed at the maximum follow-up time as presented in the KaplanMeier survival analysis to assess the improvement in performance of the survival model.
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Alterations In Genomic And Mrna Expression In Pten
We next sought to determine whether PTEN-low/miR-low TNBCs harbor common genomic alterations that may be useful diagnostically or therapeutically. To this end, we took advantage of genomic data on mutation and copy number alteration as well as mRNA expression available for these cohorts. We specifically looked for alterations in 93 genes commonly lost in BC as compiled from exome and whole genome sequencing . CNA analysis revealed significant gains of DNMT3A, and, surprisingly, of the luminal marker GATA3, as well as deletions of PTEN in the PTEN-low/miR-low tumors . These CNAs correlated with low mRNA expression of PTEN but not with high expression of DNMT3A or GATA3, the latter of which is expressed at low levels in all TNBCs . Mutational analysis revealed common alterations only in p53 . While all PTEN-low/miR-low tumors had p53 mutations, two of each group b and group c tumors lacked p53 mutation. Our CNA analysis revealed that three of the latter four tumors show no gain of its E3 ligase HDM2 and presumably harbor p53 deletions instead . Notably, p53 mutations may have dominant gain-of-function effects that promote metastasis .
Cancer Types With The Worst Outlook
While there have been some clear wins for the drug industry and medical community, other cancer types have showed only minimal progress. The following five cancer types currently have the poorest long-term outlook, based on ACS data.;
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Lymphoma Of The Breast
Non-Hodgkin lymphomas of the breast are rare and make up less than 1 in 100 breast cancers .
The most common types are B-cell lymphomas such as diffuse large B-cell lymphomas and extranodal marginal zone lymphomas. A less common type is peripheral T-cell lymphoma .;
There is a rare type of NHL called breast implant associated anaplastic large cell lymphoma . This can develop in a small number of women who have breast implants. The first sign is usually a swelling around the breast implant. Very rarely, a lump may be felt close to the implant.
For most people these symptoms happen many years after their implant surgery, but it could happen sooner.;An in situ BIA-ALCL is when the lymphoma hasnt spread into other areas of the breast. The implant is removed and;no further treatment is usually needed, but sometimes you may have drug treatment. The outlook is excellent for this type.;
In some women the lymphoma can show as a lump in the breast. This type is called infiltrative i-ALCL and it might also spread to the lymph nodes. After removing the implant, the treatment is usually chemotherapy or sometimes radiotherapy. The outlook is not so good for this type.;
Pathological Assessment Of Immune Infiltration
Vascular invasion, inflammatory cell infiltrate, and necrosis, including relation of tumor cells/tumor stroma, were evaluated on slides stained with H&E as previously described. Using a simple microscope, subjective categorization of inflammatory cell infiltrate into the categories of low, moderate, high, and severe was performed based on the frequency of mononuclear inflammatory cell infiltration observed in the invasive tumor.
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Enhancing Healthcare Team Outcomes
After the treatment of breast cancer, long-term;follow-up is necessary. There is a risk of local and distant relapse, and hence an interprofessional team approach is necessary. The women need regular mammograms and a pelvic exam. Also, women with risk factors for osteoporosis need a bone density exam and monitoring for tumor markers for metastatic disease. For those who are about to undergo radiation therapy, a baseline echo and cardiac evaluation are necessary. Even though many types of integrative therapies have been developed to help women with breast cancer, evidence for the majority of these treatments is weak or lacking.
Over the past four decades, the survival rates of most breast cancer patients have improved. Of note is that the;presence of;breast cancer has gradually slowed down over the past decade, which may be due to earlier detection and improved treatments. The prognosis for patients with breast cancer is highly dependent on the status of axillary lymph nodes. The higher the number of positive lymph nodes, the worse the outcome. In general, hormone-responsive tumors tend to;have a better outcome. In breast cancer survivors, adverse cardiac events are common; this is partly due to the cardiotoxic drugs to treat cancer and the presence of;traditional risk factors for heart disease. The onus is on the healthcare provider to reduce the modifiable risk factors and lower the risk of adverse cardiac events.;[Level 5)
How Is Prognosis Estimated
Prognosis is estimated by looking at what has happened over many years to large groups of people diagnosed with a similar cancer. However, everyones situation is different so no one can say for certain what will happen to you. Also, treatments and survival rates are constantly improving, which affects the accuracy of estimates for people being treated today.
Prognosis is described in different ways. It may be put into words or numbers. Its often expressed as a five- or ten-year survival rate. This is an estimate of how many people are likely to be alive five or ten years following their diagnosis.;
A 90% five-year survival rate means that 90 out of 100 people diagnosed with breast cancer are likely to be alive five years after their diagnosis. It doesnt mean these people will only live for five years; it just states how many people are likely to be alive at that point.
Cancer Research UK has general statistics on five- and ten-year breast cancer survival rates on;their website. Remember, these statistics are based on large groups of patients and cannot predict what will happen in your individual case.
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What Is The Prognosis Of Patients With Inflammatory Breast Cancer
The prognosis, or likely outcome, for a patient diagnosed with cancer is often viewed as the chance that the cancer will be treated successfully and that the patient will recover completely. Many factors can influence a cancer patients prognosis, including the type and location of the cancer, the stage of the disease, the patients age and overall general health, and the extent to which the patients disease responds to treatment.
Because inflammatory breast cancer usually develops quickly and spreads aggressively to other parts of the body, women diagnosed with this disease, in general, do not survive as long as women diagnosed with other types of breast cancer.
It is important to keep in mind, however, that survival statistics are based on large numbers of patients and that an individual womans prognosis could be better or worse, depending on her tumor characteristics and medical history. Women who have inflammatory breast cancer are encouraged to talk with their doctor about their prognosis, given their particular situation.
Ongoing research, especially at the molecular level, will increase our understanding of how inflammatory breast cancer begins and progresses. This knowledge should enable the development of new treatments and more accurate prognoses for women diagnosed with this disease. It is important, therefore, that women who are diagnosed with inflammatory breast cancer talk with their doctor about the option of participating in a clinical trial.
What This Means For You
If youre a man who has been diagnosed with breast cancer, this study may seem disheartening. But it does show that you need to be your own best advocate to make sure that you get the treatments that are best for your unique situation. Based on the study results, undertreatment is likely the reason for much of the survival rate difference between men and women diagnosed with breast cancer.
Its also very important to talk to your doctor right away about any changes in your breasts, including:
- nipple pain
- sores on the nipple and/or areola area
- enlarged lymph nodes under the arm
Because many men dont consider the possibility that they may develop breast cancer, they may wait a year or longer to talk to their doctor after noticing a breast symptom. This means the cancer is diagnosed at a later stage, which also contributes to higher mortality rates for men with breast cancer.
Future research should focus on why and how clinical characteristics, as well as biological features, may have different implications for the survival of male and female patients with breast cancer, the researchers concluded. Additional factors, particularly compliance to treatment, biological attributes, and lifestyle factors , should be assessed to help in developing treatments tailored for men, which would mitigate this sex-based disparity.
For more information, visit the Breastcancer.org pages on Male Breast Cancer.
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Certain Breast Cancer Subtypes Have A Better Statistical Prognosis
In general, tubular, mucinous and medullary breast carcinomas have a better prognosis than the other sub-types.
The table below gives a very general approximation of the survival rates that may be associated with the different breast cancer subtypes.
However, please bear in mind that these figures are a rough generalization only and survival will always be determined by the individual characteristics of each breast cancer and each patient.
Nonetheless, the relative aggressiveness of the different breast cancer subtypes can be interpreted from the table.
and is almost always near 100% curable.)
|breast cancer sub-type|
|Inflammatory breast carcinoma||65% 35%|
Phyllodes Or Cystosarcoma Phyllodes
Phyllodes is pronounced fill-oy-dees. This type of breast cancer makes up less than 1 in 100 breast cancers . Its also called cystosarcoma phyllodes. The first symptom is usually a lump in the breast.
Phyllodes can be either cancerous or non cancerous . It tends to occur in middle aged women or older. If cancerous, it might spread into the lymph nodes but this is rare.
Surgery is the main treatment. Sometimes you might also have;radiotherapy or chemotherapy.
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Identification Of Micrornas Whose Expression Correlates With Pten Loss In Breast Cancers Of All Subtypes Or In Tnbc
Identification of microRNAs whose expression levels most strongly correlate with Pten-low expression in TNBC. a Correlation ranking of top miRNAs with PTEN expression in TNBC. bf Kaplan-Meier curves for top five positively correlated PTEN-miRNA pairs in 205 TNBC samples in the training cohort. gj Kaplan-Meier curves for four positively correlated PTEN-miRNA pairs available in a 44 TNBC validation cohort
Additional Types Of Invasive Ductal Carcinoma:
There are four types of invasive ductal carcinoma that are less common:
- Medullary Ductal Carcinoma This type of cancer is rare and only three to five percent of breast cancers are diagnosed as medullary ductal carcinoma. The tumor usually shows up on a mammogram and it does not always feel like a lump; rather it can feel like a spongy change of breast tissue.
- Mucinous Ductal Carcinoma This occurs when cancer cells within the breast produce mucous, which also contains breast cancer cells. The cells and mucous combine to form a tumor. Pure mucinous ductal carcinoma carries a better prognosis than more common types of IDCs.
- Papillary;Carcinoma ;This is a very good prognosis breast cancer that primarily occur in women over the age of 60.
- Tubular Ductal Carcinoma ;This is a rare diagnosis of IDC, making up only two percent of diagnoses of breast cancer. The name comes from how the cancer looks under the microscope; like hundreds of tiny tubes.; Tubular breast cancer has an excellent prognosis.
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Overexpression Of Other Tyrosine Kinase Receptors
Since trastuzumab does not prevent HER3 dimerization , the overexpression of HER3 could overcome trastuzumab-mediated inhibition of HER2 signaling. It was previously found that co-expression of HER3 and HER2 is required for the transformation of NIH-3T3 cells and that HER2-HER3 dimerization results in increased tyrosine phosphorylation of HER3 which subsequently increases PI3K recruitment and downstream activation . These findings imply that cancer cells, by utilizing HER3 signaling, can compensate for the inhibition of HER2 signaling mediated by trastuzumab.
Another promising target whose aberrant expression may confer resistance to trastuzumab is insulin-like growth factor 1 receptor . Lu et al. found that ectopic expression of IGF-1R drives trastuzumab-sensitive SKBR3 cells to resistant to the therapy. Also, IGF-1R-overexpressing SKBR3 cells show significantly low levels of p27Kip1, p21Cip1 proteins, and a high level of CDK2 kinase activity . This indicates that IGF-1R-overexpressing cells, by overcoming cell cycle arrest mediated by trastuzumab contribute to the drug resistance. Interestingly, the resistance is reversed by suppression of IGF-1R signaling with recombinant IGF-binding protein-3 or by gradual heat-induced expression of the dominant-negative IGF-1R 486/STOP . This further confirms that the elevation of IGF-1R significantly contributes to trastuzumab resistance.