Breast cancer classification
Classification aspects must be carefully tested and validated, such that confounding effects are minimized, making them either true prognostic factors, which estimate disease outcomes such as disease-free or overall survival in the absence of therapy, or true predictive factors, which estimate the likelihood of response or lack of response to a specific treatment.
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.
[16][17] It grades breast carcinomas by adding up scores for tubule formation, nuclear pleomorphism, and mitotic count, each of which is given 1 to 3 points.
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.
[29] Several factors are important when reviewing reports for individual breast cancers or when reading the medical literature, and applying staging data.
It is crucial to be aware that the TNM system criteria have varied over time, sometimes fairly substantially, according to the different editions that AJCC and UICC have released.
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.
AJCC has provided web accessible poster versions of the current versions of these copyrighted TNM descriptors and groups,[30] and readers should refer to that up to date, accurate information[30] or to the National Cancer Institute (NCI)[23] or National Comprehensive Cancer Network[39] sites which reprints these with AJCC permission.
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.
[41] Conversely, triple negative cancer (i.e. no positive receptors), lacking targeted treatments, now has a comparatively poor prognosis.
Proposed molecular subtypes include: Lower expression of: Low expression of: Similar to luminal A but: Traditional DNA classification was based on the general observation that cells that are dividing more quickly have a worse prognosis, and 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 ploidy, are 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.
[39] Some commentators prefer this approach, claiming a higher correlation than receptor immunohistochemistry with response to trastuzumab, a targeted therapy, but guidelines permit either testing method.
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.
[60][61] The most heavily marketed are: 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.
[49][61] Although these gene-expression profiles look at different individual genes, they seem to classify a given tumor into similar risk groups and thus provide concordant predictions of outcome.
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.
[71] Oncotype DX has been endorsed by the American Society of Clinical Oncology (ASCO)[60][63] and the National Comprehensive Cancer Network (NCCN).
[72] The U.S. Food and Drug Administration (FDA) does not mandate approval of this class of tests if they are performed at a single, company-operated laboratory[73] 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.
[73] The MammaPrint gene pattern is a commercial-stage 70-gene panel marketed by Agendia,[74] that was developed in patients under age 55 years who had lymph node negative breast cancers (N0).
[76] One method of assessing the molecular subtype of a breast cancer is by BluePrint,[77] a commercial-stage 80-gene panel marketed by Agendia, either as a standalone test, or combined with the MammaPrint gene profile.
Combining these newer medicines with older agents such as 6-Thioguanine (6TG) may overcome the resistance that can arise in BRCA cancers to PARP inhibitors or platinum-based chemotherapy.
[83] DNA methylation patterns can epigenetically affect gene expression in breast cancer and may contribute to some of the observed differences between genetic subtypes.
[84] 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.
[88] The medical utility of potential biomarkers of tamoxifen responsiveness such as HOXB13,[89] PAX2,[90] and estrogen receptor (ER) alpha and beta isoforms interaction with SRC3[91][92] have all yet[when?]
Computer models consider several traditional factors concurrently to derive individual survival predictions and calculations of potential treatment benefits.
is based on US cohorts[93] and presents colored bar charts that display information that may assist in decisions regarding systemic adjuvant therapies.
[98] The USC/Van Nuys prognostic index (VNPI) classifies ductal carcinoma in situ (DCIS) into dissimilar risk categories that may be treated accordingly.
