Grading of carcinoma is most often done after a treating physician and/or surgeon obtains a sample of suspected tumor tissue using surgical resection, needle or surgical biopsy, direct washing or brushing of tumor tissue, sputum cytopathology, etc. A pathologist then examines the tumor and its stroma, perhaps utilizing staining, immunohistochemistry, flow cytometry, or other methods. Finally, the pathologist classifies the tumor semi-quantitatively into one of three or four grades, including:

Grade 1, or well differentiated: there is a close, or very close, resemblance to the normal parent tissue, and the tumor cells are easily identified and classified as a particular malignant histological entity;
Grade 2, or moderately differentiated: there is considerable resemblance to the parent cells and tissues, but abnormalities can commonly be seen and the more complex features are not particularly well-formed;
Grade 3, or poorly differentiated: there is very little resemblance between the malignant tissue and the normal parent tissue, abnormalities are evident, and the more complex architectural features are usually rudimentary or primitive;
Grade 4, or undifferentiated carcinoma: these carcinomas bear no significant resemblance to the corresponding parent cells and tissues, with no visible formation of glands, ducts, bridges, stratified layers, keratin pearls, or other notable characteristics consistent with a more highly differentiated neoplasm.Although there is definite and convincing statistical correlation between carcinoma grade and tumor prognosis for some tumor types and sites of origin, the strength of this association can be highly variable. It may be stated generally, however, that the higher the grade of the lesion, the worse is its prognosis.
Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer later that year. Results of a Phase II trial in the neoadjuvant setting, NeoSphere, published in 2012, and results of a Phase II cardiac safety study in the same population, Tryphaena, published in 2013. The FDA approved the neoadjuvant indication in 2013. Pertuzumab was approved for medical use in the European Union in 2013. Society and culture
Economics
As of 2016, in the US each cycle of the three-drug combination given every three weeks costs around US$8,500, not including ancillary care costs.In the UK, a NICE evaluation in 2015, made a preliminary finding that the drug combination was not cost effective, and NICE rejected the drug in the neoadjuvant setting in May 2016, primarily because it was unknown if the drug combination provided a survival benefit. This decision was subsequently reversed six months later and pertuzumab became the first new breast cancer drug to be approved by NICE for routine NHS funding in almost a decade
after Roche pledged to provide the drug to the NHS at an undisclosed discount for patients in the neoadjuvant setting and to share the long–term financial risks. References
Further reading
Dean L (2015). "Pertuzumab Therapy and ERBB2 (HER2) Genotype". In Pratt VM, McLeod HL, Rubinstein WS,  et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520364. Bookshelf ID: NBK315949. External links
"Pertuzumab". Drug Information Portal. U.S. National Library of Medicine.