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Download scientific diagram | Microcalcifications in Van Nuys group 3 DCIS. Calcificaciones mamarias: descripción y clasificación según la 5.a edición BI-. Download scientific diagram | Van Nuys group 1 DCIS in a year-old woman. Calcificaciones mamarias: descripción y clasificación según la 5.a edición BI-. There is controversy and confusion regarding therapy for patients with ductal carcinoma in situ (DCIS) of the breast. The Van Nuys Prognostic.

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Breast cancer classification divides breast cclasificacion into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the expression of proteins and genes. As knowledge of cancer cell biology develops these classifications are updated.

The purpose of classification is to select the best treatment. The effectiveness of a specific treatment is demonstrated for a specific breast cancer usually by randomized, controlled trials. That treatment may not be effective in a different breast cancer. Some breast cancers are aggressive and life-threatening, and must be treated with aggressive treatments that have major adverse effects.

Other breast cancers are less aggressive and can be treated with less aggressive treatments, such as lumpectomy. Treatment algorithms rely on breast cancer classification to define specific subgroups that are each treated according to the best evidence available.

Classification aspects must be carefully tested and validated, such that confounding effects are minimized, making them either true prognostic factorswhich estimate disease outcomes such as disease-free or overall survival in the absence of therapyor true predictive factorswhich estimate the likelihood of response or lack of response to a specific treatment. Classification of breast cancer is usually, but not always, primarily based on the histological appearance of tissue in the tumor.

A variant from this approach, defined on the basis of physical exam findings, is that inflammatory breast cancer IBCa form of ductal carcinoma or malignant cancer in the ducts, is distinguished from other carcinomas by the inflamed appearance of the affected breast, which correlates with increased cancer aggressivity.

Breast cancers can be classified by different schemata. Each of these aspects influences treatment response and prognosis.

Description of a breast cancer would optimally include all of these classification aspects, as well as other findings, such as signs found on physical exam. A full classification includes histopathological typegradestage TNMreceptor statusand the presence or absence of genes as determined by DNA testing:. Histopathologic classification is based upon characteristics seen upon light microscopy of biopsy specimens. The three most common histopathological types collectively represent approximately three-quarters of breast cancers:.

The World Health Organization Clasiflcacion classification of tumors of the breast [7] which includes benign generally harmless tumors and malignant cancerous tumors, recommends the following pathological types:. Other well-accepted subtypes of metaplastic mammary carcinoma thought to have clinical significance but not included in the decade old WHO classification:. The grading of a cancer in the breast depends on the microscopic similarity of breast cancer cells to normal breast tissue, and classifies the cancer as well differentiated low-grademoderately differentiated intermediate-gradeand poorly differentiated high-gradereflecting progressively less normal appearing cells that have a worsening prognosis.

Although grading is fundamentally based on how biopsied, cultured cells behave, in practice the grading of a given cancer is derived by assessing the cellular clqsificacion of the tumor. The closer the appearance of the cancer cells to normal cells, the slower their growth and the better the prognosis. If cells are not well differentiated, they will appear vxn, will divide more rapidly, and will tend huys spread.

Well differentiated is given a grade of 1, moderate is grade 2, while poor or undifferentiated is given a higher grade of 3 or 4 depending upon the scale used. The Nottingham also called Elston-Ellis modification [8] of the Scarff-Bloom-Richardson grading system[9] [10] is recommended, [11] which grades breast carcinomas by adding up scores for tubule formationnuclear pleomorphismand mitotic counteach of which is given 1 to 3 points.

The scores for each of these three criteria are then added together to give an overall final score and corresponding grade as follows. This parameter assesses what percent of the tumor forms normal duct structures.

In cancer, there is a breakdown of the mechanisms that cells use to attach to each other and communicate with each other, to form tissues such as ducts, so the tissue structures become less orderly. This parameter assesses whether the cell nuclei are uniform like those in normal breast duct epithelial cells, or whether they are larger, darker, or irregular pleomorphic.

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In cancer, the mechanisms that control genes and chromosomes in the nucleus break down, and irregular nuclei and pleomorphic changes are signs of abnormal cell reproduction.

The cancer areas having cells with the greatest cellular abnormalities should be evaluated. This parameter assesses how many mitotic figures dividing cells the pathologist sees in 10x high power microscope field. One of the hallmarks of cancer is that cells divide uncontrollably. The clasifivacion cells that are dividing, the worse the cancer. Mitotic figures are counted only at the periphery of the tumor, and counting should begin in the most mitotically active areas.


The scores for each of these three criteria are added together to give a final overall score and a corresponding grade as follows:. Lower-grade tumors, with a more favorable prognosis, can be treated less aggressively, and have a better survival rate. Higher-grade tumors are treated more aggressively, and their intrinsically worse survival rate may warrant the adverse effects of more aggressive vam. Staging [12] is the process of determining how much cancer there is in the body and where it is located.

The underlying purpose of staging is to describe the extent or severity of an individual’s cancer, and to bring together cancers that have similar prognosis and treatment. Staging information that is obtained prior to surgery, for example by mammography, x-rays and CT scans, is called clinical staging and staging by surgery is known as pathological staging. Pathologic staging is more accurate than clinical staging, but clinical staging is the first and sometimes the only staging type.

For example, if clinical staging reveals stage IV disease, extensive surgery may not be helpful, and appropriately incomplete pathological staging information will be obtained. Their TNM system, which they now develop jointly, first classifies cancer by several factors, T for t umor, N for n odes, M for m etastasis, and then groups these TNM factors clasificaciob overall stages. Although TNM classification is an internationally agreed system, it has gradually evolved through its different editions; the dates of publication and of adoption for use of AJCC editions is summarized in cllasificacion table in this article; past editions are available from AJCC for web download.

Several factors are important when reviewing reports for individual breast cancers or when reading the medical literature, and applying staging data. As a result, a given stage may have quite a different prognosis depending on which staging edition is used, independent of any changes in diagnostic methods or treatments, an effect that can contribute to “stage migration”. As a practical matter, reports often use the staging edition that was in place when the study began, rather than the date of acceptance or publication.


However, it is worth checking whether the author updated the staging system during the study, or modified the usual classification rules for specific use in the investigation. A different effect on staging arises from evolving technologies that are used to assign patients to particular categories, such that increasingly sensitive methods tend to cause individual cancers to be reassigned to higher stages, making it improper to compare that cancer’s prognosis to the historical expectations for that stage.

Finally, of course, a further important consideration is the effect of improving treatments over time as well. TX refers to an inability to assess that site; Tis refers to DCISLCISor Paget’s disease ; T4d refers to inflammatory breast cancera clinical circumstance where typical skin changes involve at least a third of the breast. The present TNM edition no longer uses the MX option, and allocates tumors to one of three clinical categories: The impact of different stages on outcome can be appreciated in the following table, published in a textbook, [26] which shows the observed 5-year overall survival of over 50, patients from who were reclassified using the AJCC 5th edition criteria; the data is also available in the AJCC source, [17] which also gives the relative survival rate in comparison to an age-matched actually, age- sex- and race-matched population.

The receptor status of breast cancers has traditionally been identified by immunohistochemistry IHCwhich stains the cells based on the presence of estrogen receptors ERprogesterone receptors PR and HER2. This remains the most common method of testing for receptor status, but DNA multi-gene expression profiles can categorize breast cancers into molecular subtypes that generally correspond to IHC receptor status; one commercial source is the BluePrint test, as discussed in the following section.

Receptor status is a critical assessment for all breast cancers as it determines the suitability of using targeted treatments such as tamoxifen and or trastuzumab. These treatments are now some of the most effective adjuvant treatments of breast cancer. Efforts are underway to utilize this as prognostic marker and treatment. Receptor status was traditionally considered by reviewing each individual receptor ER, PR, her2 in turn, but newer approaches look at these together, along with the tumor gradeto categorize breast cancer into several conceptual molecular classes [33] that have different prognoses [11] and may have different responses to specific therapies.

Proposed molecular subtypes include:. Traditional DNA classification was based on the general observation that cells that are dividing more quickly have a worse prognosisand relied on either the presence of protein Ki67 or the percentage of cancer cell DNA in S phase.

These methods, and scoring systems that used DNA ploidyare used much less often now, as their predictive and prognostic power was less substantial than other classification schemes such as the TNM stage. In contrast, modern DNA analyses are increasingly relevant in defining underlying cancer biology and in helping choose treatments. DNA microarrays have compared normal cells to breast cancer cells and found differences in the expression of hundreds of genes.

Although the significance of many of those genetic differences is unknown, independent analyses by different research groups has found that certain groups of genes have a tendency to co-express. These co-expressing clusters have included hormone receptor-related genes, HER2 -related genes, a group of basal-like genes, and proliferation genes.


As might therefore be anticipated, there is considerable similarity between the receptor and microarray classifications, but assignment of individual tumors is clasificacipn no means identical. Which classification scheme receptor IHC or DNA expression profile more reliably assorts particular cancers to effective therapies is under investigation.

Several commercially marketed DNA microarray tests analyze clusters of genes and may help decide which possible treatment is most effective for a particular cancer. No tests have been verified by Level I evidencewhich is rigorously defined as being derived from a prospectiverandomized controlled trial where patients who used the test had a better nuy than those who did not.

Acquiring extensive Level I evidence would be clinically and ethically challenging. However, several validation approaches [44] [45] are being actively pursued. Numerous genetic profiles have been developed. These multigene assays, some partially and some completely commercialized, have been scientifically reviewed to compare them with other standard breast cancer classification methods such as grade and receptor status.

Although there is considerable evidence that these tests can refine the treatment decisions in a meaningful proportion of breast cancers vsn [47] they are fairly expensive; proposed selection criteria for which particular tumors may benefit by being interrogated by these assays [11] remain controversialparticularly with lymph node positive cancers. Oncotype DX assesses 16 cancer-related genes and 5 normal comparator reference genes, and is therefore sometimes known as the gene assay.

It was designed for use in estrogen receptor ER positive tumors.

Breast cancer classification

The test is run on formalin fixed, paraffin-embedded tissue. Oncotype results are reported as a Recurrence Score RSwhere a higher RS is associated with a worse prognosisreferring to the likelihood of recurrence without treatment. In addition to that prognostic role, a higher RS is also associated with a higher probability of response to chemotherapywhich is termed a positive predictive factor.

A summary of clinical trials using Oncotype is included in the Oncotype DX main article. These results suggest that not only does Oncotype stratify estrogen-receptor positive breast cancer into different prognostic groups, but also suggest that cancers that have a particularly favorable Oncotype DX microarray result tend to derive minimal benefit from adjuvant chemotherapy and so it may be appropriate to choose to avoid side effects from that additional treatment.

As an additional example, a neoadjuvant clinical treatment program that included initial chemotherapy followed by surgery and subsequent additional chemotherapy, radiotherapyand hormonal therapy found a strong correlation of the Oncotype classification with the likelihood of a complete response CR to the presurgical chemotherapy.

Since high risk features may already be evident in many high risk cancers, for example hormone-receptor negativity or HER-2 positive disease, the Oncotype test may especially improve the risk assessment that is derived from routine clinical variables in intermediate risk disease. Food and Drug Administration FDA does not mandate approval of this class of tests if they are performed at a single, company-operated laboratory [59] Genomic Health, which developed Oncotype DX, offers the test under these so-called home brew rules and, accordingly, to that extent the Oncotype DX assay is not specifically FDA approved.

The MammaPrint gene pattern is a commercial-stage gene panel ce by Agendia, [60] that was developed in patients under age 55 years who had lymph node negative breast cancers N0. MammaPrint traditionally used rapidly frozen tissue [11] but a room temperature, molecular fixative is available for use within 60 minutes of obtaining fresh tissue samples. A summary of clinical trials clasificzcion MammaPrint is included in the MammaPrint main article.

To be eligible for the MammaPrint gene expression profilea breast cancer should have the following characteristics: In the US, df tumor should also be lymph node negative N0 nnuys, but internationally the test may be performed if the lymph nyus status is negative or positive with up to 3 nodes.

One method of assessing the molecular subtype of a breast cancer is by BluePrint, [63] a commercial-stage gene panel marketed by Agendia, either as a standalone test, or combined with the MammaPrint gene profile. The choice of established chemotherapy medications, if chemotherapy is needed, may also be affected by DNA assays that predict relative resistance or sensitivity.

Various molecular pathway targets and DNA results are being incorporated in the design of clinical trials of clasificwcion medicines. DNA methylation patterns can epigenetically affect gene expression in breast cancer and may contribute to some of the observed differences between genetic subtypes. Tumors overexpressing the Wnt signaling pathway co-receptor low-density lipoprotein receptor-related protein 6 LRP6 may represent a distinct subtype of breast cancer and a potential treatment target.

Numerous clinical investigations looked at whether testing for variant genotype polymorphic alleles of several genes could predict whether or not to prescribe tamoxifen ; this was based on possible differences in the rate of conversion of tamoxifen to the active metabolite, endoxifen. Although some studies had suggested a potential advantage from CYP2D6 testing, data from two large clinical trials found no benefit.