BREAST HISTOPATHOLOGY: OLD AND NEW CHALLENGES
Authors: Going J. 
Published: August 2006

Background:  The last 20 years have seen substantial improvement in survival of women with breast cancer, unlike other common cancers. Possible explanations include new treatments, and better use of old treatments. Mainstays of breast cancer treatment remain surgery, radiotherapy and chemotherapy; none are new fields and no single event in these fields has been revolutionary. But how we work has evolved. Quality control has improved standards in breast cancer, and strengthened teamwork, so more women get the right treatment. Histopathology has a crucial role in this. Showing that breast cancer can be reproducibly graded, for instance, and that grade is a key prognostic factor, paved the way for the Nottingham Prognostic Index (NPI).Meeting challenges:  Until molecular prognostics are more cost‐effective than what we do now, it's important that we do established things well. Breast cancer grading is neither easy nor unchallenging. Accurate grading requires meticulous attention to specimen prosection, fixation, tissue processing, section cutting and staining, and grading criteria must be understood clearly and followed precisely. Evaluating expression of sex steroid receptors is important for predicting whether a breast cancer will respond to endocrine manipulation. For many years biochemical assays were the mainstay of oestrogen receptor (ER) testing, but a false positive could result from normal glandular breast tissue in the tumour sample, or a false negative if the sample did not, in fact, contain tumour. Immunohistochemistry revolutionised ER assay: the pathologist could now see which cells were expressing ER. Careful attention to detail is still required: if the assay is not sensitive enough, ER+ cancers may be missed. External quality assurance (EQA) schemes guard against this. New immunohistochemical assays present new challenges. Only cancers in which erbB2 / Her2 expression is significantly increased relative to normal breast tissue may benefit from trastuzumab. In this situation, a maximally sensitive assay is not desirable, as it will cause (false) positive staining of cancers which do not over‐express of Her2. Considerable effort has been expended in pursuit of this goal, without complete success. The widely used ‘Herceptest’ is based on a polyclonal antibody and some users find lot‐to‐lot variation in sensitivity. Observers may differ in their interpretation of the test. Ambiguous (‘2+’) results from immunohistochemistry are usually resolved by fluorescence in situ hybridisation, which presents its own challenges. Regulatory agencies in the UK determined in June 2006 that trastuzumab is cost‐effective adjuvant therapy for Her2‐positive breast cancer. But trastusumab is toxic (it can compromise ventricular function and some women develop frank heart failure). As trastuzumab has no benefit in cancers which do not over‐express Her2, getting Her2 testing right crucial if its benefits are to be realised. This will require close attention to internal and external QA.Conclusions:  Histopathology remains crucial in breast cancer management. It will evolve, as new demands for information emerge. Breast pathology in 2026 will be a hybrid of old and new, based on sound evidence, different but not unrecognisably different to what we are familiar with today.