Five Top Stories in Breast Pathology

Abstract

The past decade has seen an immense growth in our understanding of the molecular basis of breast cancer initiation, progression, and metastasis. This has also led to development of new ancillary studies that are commonly used in clinical practice for evaluation of breast tumors. These include diagnostic and predictive biomarkers using immunohistochemistry and other molecular pathology techniques as the method of detection. Minimally invasive surgery such as breast-conserving surgery and sentinel lymph node sampling has become the standard of care in the surgical management of breast cancer. Studies have also identified potential new targets of therapy within these molecular pathways. With the fast pace of growth in our knowledge, practicing physicians, including pathologists, are expected to have a sound understanding of not only the morphologic alterations but also the diagnostic and predictive biomarkers and molecular pathology of breast cancer to practice state-of-the-art pathology in this era of personalized medicine. Pathologists are consultants to their clinical colleagues on matters related to the diagnosis of breast cancer and predicting its behavior that has clinical implications. It is therefore important for pathologists to be familiar with published and ongoing clinical trials in the surgical, medical, and radiation oncology fields related to breast cancer so they can give a better informed and educated opinion when discussing cases.The 5 stories on breast pathology in this issue of Archives of Pathology & Laboratory Medicine aim to give an overview of the changing field of breast pathology to practicing pathologists who are busy with their work, and this one-stop approach may be valuable to them. The senior authors of these 5 stories include experienced practicing pathologists with years of experience in the practice of breast pathology and molecular diagnostic oncology.Immunohistochemistry has become an integral part of diagnostic pathology, and so the first story in this series is on the role of immunohistochemistry in the diagnosis of breast lesions. The article draws evidence from published data and the authors' personal experience to review the importance of immunohistochemistry in the differential diagnosis of breast lesions, emphasizing the importance of various biomarkers with their potential pitfalls and limitations. This is followed by an article on fibroepithelial tumors of breast, including fibroadenoma and phyllodes tumor, covering diagnostic morphologic challenges in their differential diagnosis, especially on needle core biopsy, and the potential albeit limited role of immunohistochemistry that may aid in the pathologic diagnosis. Possible molecular mechanisms involved in the initiation and progression of phyllodes tumor are also discussed.Triple-negative breast cancer—that is, tumors negative for estrogen receptor, progesterone receptor, and HER2—is a small subset of breast cancer that has become important because of the lack of traditional hormonal modulation or HER2 targeting therapy and ongoing studies in search of a molecular target in controlling the growth of these tumors. This subgroup presents many faces (“The Good, the Bad, and the Ugly”) of triple-negative breast cancer, and although the majority are basal-like with an aggressive biology, some tumors, such as adenoid cystic carcinoma, have a better prognosis than the same stage of invasive ductal carcinoma not otherwise specified. The third article in the series elaborates the basal-like carcinoma in the subset of triple-negative breast cancer, emphasizing the importance of morphologic correlation with the immunophenotype in the subclassification of triple-negative breast cancer. The next paper in the series, titled “Theranostic and Molecular Classification of Breast Cancer,” discusses the predictive biomarkers in breast cancer along with the evolution of the field of molecular diagnostic oncology, which is beginning to dictate adjuvant treatment. The decade since the publication of the first paper1 on molecular portraits of breast cancer in 2000 has seen a flurry of activity in the publication of papers in the field of molecular classification of breast cancer. The article discusses various molecular-based tests that have now entered the arena of clinical practice, such as the 70-gene panel MammaPrint2 and the 21-gene reverse transcription-polymerase chain reaction–based Oncotype DX.3 The senior author of this article is a practicing pathologist and a director of molecular diagnostic oncology who, in addition to the published literature, has brought his own personal perspective to the discussion of the available tests. The paper also includes highly practical issues that have been discussed for many years in breast pathology, such as evaluation of estrogen receptor, progesterone receptor, and HER2. These tests have become the standard of care, and having a thorough understanding of the pitfalls in evaluation of these biomarkers is critical, as they not only serve as predictive markers, but also, in the case of HER2, have become one of the success stories in targeted cancer therapy. The College of American Pathologists/American Society of Clinical Oncology guidelines4,5 relating to the evaluation of estrogen receptor, progesterone receptor, and HER2 are discussed in this paper.Sentinel lymph node biopsy, introduced in the early 1990s for regional lymph node staging in breast cancer, has now become the standard of care. The past 2 decades have seen an increase in our experience in the technique of performing sentinel lymph node biopsy and histopathologic examination of lymph nodes, including intraoperative evaluation. The final story in this special section discusses the history of the evolution of sentinel lymph node biopsy in breast cancer and the changing practice, especially during the past couple of years, after the publication of 2 prospective clinical trials, the NSABP B326 and the American College of Surgeons Z0011 trial.7 Coauthors include a breast surgical oncologist and breast pathologists, and together they not only discuss the published data but also bring their perspective and outline their own practice with decreasing use of intraoperative evaluation of sentinel lymph node biopsy.The 5 articles in this special section present information that we hope will be valuable and of practical importance for the practicing pathologist. Breast cancers, like most tumors, are managed by a multidisciplinary approach, so it is important for the pathologist to be well versed in not only the advances in the pathology of breast cancer but also related fields such as surgical and medical oncology.