Rosen's Breast Pathology, 4e

xv

Introduction

clearly displaying the name of the patient and the accession number corresponding to the slides and paraffin blocks enclosed. It is unacceptable and substandard practice to withhold the pathology report previously obtained from a consultant or second-opinion institution so as not to “bias” the second review. The pathology report provides essential information such as an index of location(s) of the specimen(s) represented by individual slides, a description of the gross appearance of the specimen(s), clinical informa- tion provided with the specimen, frozen section interpreta- tions, and details of the originating pathologist’s diagnosis. The pathology report must be included even if a final diag- nosis had not been reached. When the slides are sent directly from one laboratory to another in relation to a clinical consultation at the recipient institution, the correspondence should include the name of the clinical physician who is be- ing consulted (if known) and detailed billing information. When more than one consultant is involved, it is vital that all consultants examine the same or equivalent material. A host of new classifications of breast carcinoma have emerged from studies using tissue microarray and gene expression profile technology. 17–23 Some of these molecular- based classification schemes have led to the introduction of testing procedures that assign patients to prognostic catego- ries and predict response to therapy, as discussed in Chapter 45. Some of these tests are being used in clinical practice based on analysis of retrospective data. It will take many years before they are fully validated in prospective clinical trials. As the results of additional gene profiling studies are reported, more classifications will no doubt be developed and promoted for various reasons. The exceptional speed with which the molecular study of breast carcinoma has advanced makes it hazardous to predict circumstances even a few years hence. Nevertheless, the cur- rent situation was perhaps best summarized by Rakha and Ellis 22 in their paper titled “Modern Classification of Breast Cancer: Should We Stick with Morphology or Convert to Molecular Profile Characteristics,” wherein they observed that the “replacement of conventional classification seems unfounded and incorporation of multigene molecular clas- sifiers to conventional BC [breast carcinoma] classification systems seems more realistic and practical to support more effective tailoring of therapy in the future.” In a report titled “Breast Cancer Prognostic Classification in the ­Molecular Era: The Role of Histological Grade,” Rakha et al. 21 con- cluded that “clinical acceptance of these molecular assays will require them to be more than expensive surrogates for established traditional factors such as histological grade.” A study reported by Sotiriou et al. 24 illustrates how results from gene expression profiling can be complementary to Molecular versus Morphology for the Classification of Breast Carcinoma: Must It Be Either/Or?

conventional pathologic data. The investigators developed a scoring system or gene expression grade index based on a 97-gene list that correlated patterns of gene expression with histologic grade. A high gene expression grade index was associated with 86% of grade 3 tumors, and a low index was associated with 91% of grade 1 tumors. The contribu- tion of the gene expression index was greatest among grade 2 carcinomas, in which a high index was associated with a significantly greater risk for recurrence than a low index ( p < 0.001; hazard ratio, 3.61; CI, 2.25 to 5.78). Finally, there are substantial parts of the world where the technology needed to support a molecular-based descrip- tion of breast carcinoma is unavailable. This situation is not likely to change soon and will require the continued use of standard morphology-based diagnostic reporting. It would be wise to observe this rapidly evolving field with a healthy dose of skepticism regarding the likelihood that any of the current molecular-based classification schemes will soon supplant standard pathologic examination as the basis for establishing a diagnosis, estimating prognosis, and for fundamental treatment decisions. At best, molecular data in its current form complement pathologic observa- tions and can “fine tune” therapeutic decisions, especially in intermediate or ambiguous situations. Ever since it was demonstrated in the 1970s and 1980s that mammography screening could detect clinically occult carci- nomas of the breast and reduce breast carcinoma mortality, concern has been expressed that screening results in “over- diagnosis” and “overtreatment” because it identifies indolent lesions that are unlikely to have a fatal outcome and could be left untreated. The issue first came to a head in the late 1970s when the early results of the Breast Cancer ­Diagnosis Demonstration Project (BCDDP) sponsored by the National Cancer Institute (NCI) and the American ­Cancer Society (ACS) were presented. The BCDDP program, inspired by the breast screening initiative carried out by the Health Insur- ance Plan of Greater New York (HIP) in the 1960s, consisted of 29 mammography centers in 27 ­cities across the United States that were created to assess the feasibility of nationwide breast screening by this method. A total of 283,222 women enrolled for five annual screening examinations between 1973 and 1980. The 1977 report revealed that screening on this scale could be accomplished and that clinically occult carcinomas were detected. The program came under fire for leading to “overdiagnosis” and “overtreatment” as evidenced by the large proportion of biopsies from lesions that proved to be benign, the detection of a small number of benign lesions that were misdiagnosed as carcinoma, and treat- ment for “indolent” carcinomas that might not have become clinically apparent in the patient’s lifetime. There was also concern that radiation exposure during screening might DCIS by Any Other Name Is Still Carcinoma