A Brief Overview of the WHO Classification of Breast Tumors, 4th Edition, Focusing on Issues and Updates from the 3rd Edition
TL;DR: This review of the WHO classification of Tumors of the Breast has focused on invasive carcinomas, precursor lesions, and some benign epithelial proliferations.
Abstract: The WHO Classification of Tumors of the Breast, 4th edition, is an update to the 3rd edition that was published in 2003, and covers all neoplastic and preneoplastic lesions of the breast. Changes to the 4th edition include new aspects and changes to the terminology that reflect our present-day knowledge of these lesions. Definitions for histopathological diagnosis are complemented by a description of clinical features, epidemiology, macroscopy, genetics, and prognostic and predictive features. In this review of the WHO classification, we have focused on invasive carcinomas, precursor lesions, and some benign epithelial proliferations.
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TL;DR: In this article, the authors presented a new version of the版 format, called新版, which was used for the first time in 2003 and 2012, and showed that it was more effective than the previous versions.
Abstract: 与2003年WHO乳腺肿瘤第3版分类（简称旧版分类）相比［1］，国际癌症研究机构（IARC）近期发表的2012年WHO乳腺肿瘤组织学第4版分类（简称新版分类）充分体现了近10年来乳腺肿瘤病理学的发展［2］。新版分类仍以形态学特征为骨架，但更加注重病理类型、分子生物学和临床治疗的关系。我们对新、旧版分类方法的一些要点和变化试谈几点体会，供同道参考。
258 citations
TL;DR: The notion that cancer cells are able to switch between different modes of migration asks for a thorough review of the actual relevance of EMT in cancer metastasis.
176 citations
Cites background from "A Brief Overview of the WHO Classif..."
...special type (previously termed invasive ductal carcinoma) [112]....
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TL;DR: The understanding of breast cancer has evolved from the early description of the disease around 460 BCE as “black bile-containing crab-like tumors” to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients.
Abstract: Background Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an “excess of black bile” and treatment options including the use of opium and castor oil, prevailed. Surgical resection was introduced in the 18th century. The advent of modern medicine led to the development of novel treatment options that include hormonal, targeted and chemo-therapies. There are still several therapeutic challenges including the treatment of triple negative breast cancer (TNBC), and overcoming drug resistance. Scope of review The increased incidence and awareness of breast cancer has led to significant changes in diagnosis and treatment in recent decades. But, mankind has come a long way. Herein, I have traced how our understanding of breast cancer has evolved from the early description of the disease around 460 BCE as “black bile-containing crab-like tumors” to the conventional as a heterogeneous disease with high degree of diversity between and within tumors, as well as among breast cancer patients. How is breast cancer treated today and how do risk factors, breast cancer subtype and drug resistance contribute to the therapeutic challenges at the turn of the 21st century? Major conclusions Breast cancer remains a serious public health issue worldwide. However, appreciable growth in our understanding of breast cancer in the past century has led to remarkable progress in the early detection, treatment and prevention of the disease. The clinical focus is shifting more towards tailored therapy as more targets are characterized and novel highly innovative approaches are developed. General significance Tracing the history of breast cancer, highlights how increased awareness of the disease, and progress in research and development have enhance our understanding of the disease.
158 citations
TL;DR: The 2013 update of the AGO Breast Committee guidelines has downgraded the available version 8.0 of Adjuvant! online and recommends the clinical use of Ki-67 under the prerequisite of meticulous quality control.
Abstract: For the last 12 years, the Breast Committee of the Arbeitsgemeinschaft Gynakologische Onkologie (German Gynaecological Oncology Group, AGO) has been preparing and updating evidence-based recommendations for the diagnosis and treatment of patients with early and metastatic breast cancer. The AGO Breast Committee consists of 43 gynaecological oncologists specialized in breast cancer and interdisciplinary members specialized in pathology, radiological diagnostics, medical oncology and radiotherapy. The update is performed according to documented rules by thoroughly reviewing and scoring chapter by chapter the recent publications for their scientific validity (Oxford Level of Evidence, LoE; www.cebm.net[1]) and clinical relevance (AGO Grades of Recommendation; table table1).1). Here we present the 2013 update of these guidelines focussing on the modifications that were performed this year. The full version of the update is available online as a PDF file in an English and a German version [2].
Table 1
AGO grades of recommendation
Prognostic and Predictive Factors
Currently, the indication for adjuvant chemotherapy is mainly driven by prognosis and to a much lesser extent by prediction. Since the publication of the molecular classification of breast cancer, the role of classical pathology and immunohistochemistry (IHC) has been questioned as a sole instrument for adjuvant decision making. According to ASCO-CAP guidelines, discordances for central versus local immunohistochemical staining of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) are reported in about 20%, major discrepancies in grading for 40% [3,4,5]. Furthermore, in 2012, Mirror trialists reported an upgrade of 22% of pN0 cases to pN1 in central pathology [6]. In the context of these data, and because of the lack of consideration of HER2 over-expression as a prognostic and predictive factor, the AGO guidelines have downgraded the available version 8.0 of Adjuvant! online (LoE 2bB; AGO+/-). Considering immunohistochemical tumour markers, Ki-67 is a reliable prognostic factor especially after neoadjuvant chemotherapy (NACT)/short-term endocrine treatment. Data for prediction of chemotherapy outcome are less convincing. The committee nevertheless recommends the clinical use of Ki-67 under the prerequisite of meticulous quality control (LoE 1aA; AGO+). As long as nationwide standardization and quality assurance are not implemented, cut-off levels cannot be reliably defined for routine use.
uPA/PAI was tested in prospective trials and is suggested as a reliable prognostic marker and a predictive marker for the usefulness of chemotherapy in N0 cases (LoE 1aA; AGO+).
New molecular tools (mRNA, DNA level) have the advantage of higher accuracy, reproducibility and lower inter-observer variability compared to IHC. To allow for adequate evaluation of available molecular markers/genomic signatures, the AGO Breast Committee valued prospective-retrospective evidence, generated by retrospective analyses using archived tissue from prospective trials, to LoE IB as proposed by Simon et al. in 2009 [7]. Validated molecular signatures may be used in individual cases in which classical prognostic factors provide contradictory results; however, a general recommendation cannot be given for lack of prospective data (LoE 2bB; AGO+/-). The largest prospective-retrospective body of evidence exists for Oncotype DX® (Genomic Health Inc., Redwood City, CA, USA) (LoE IB, prognostic and predictive for chemotherapy) in HR+/N0-1 breast cancer [8,9]. Endopredict® (Sividon Diagnostics GmbH, Cologne, Germany) (LoE IB for prognosis) was evaluated in HR-positive postmenopausal patients receiving endocrine therapy only and cannot be used for prediction of chemotherapy outcome [10]. Mammaprint® (Agendia BV, Amsterdam, Netherlands) has been evaluated in N0-1 breast cancer (LoE IIC for prognosis) [11]. Additionally, PAM50, a gene expression signature which reproduces molecular subtypes (LoE IIB for prognosis), will soon be commercially available in Germany [12].
141 citations
TL;DR: An overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting is given, then the latest important trends in designing breast cancer nanomedICine are discussed, including passive and active cancer cell targeting, breast cancer stem celltargeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer.
Abstract: Breast cancer is the most common malignant disease in women worldwide, but the current drug therapy is far from optimal as indicated by the high death rate of breast cancer patients. Nanomedicine is a promising alternative for breast cancer treatment. Nanomedicine products such as Doxil® and Abraxane® have already been extensively used for breast cancer adjuvant therapy with favorable clinical outcomes. However, these products were originally designed for generic anticancer purpose and not specifically for breast cancer treatment. With better understanding of the molecular biology of breast cancer, a number of novel promising nanotherapeutic strategies and devices have been developed in recent years. In this review, we will first give an overview of the current breast cancer treatment and the updated status of nanomedicine use in clinical setting, then discuss the latest important trends in designing breast cancer nanomedicine, including passive and active cancer cell targeting, breast cancer stem cell targeting, tumor microenvironment-based nanotherapy and combination nanotherapy of drug-resistant breast cancer. Researchers may get insight from these strategies to design and develop nanomedicine that is more tailored for breast cancer to achieve further improvements in cancer specificity, antitumorigenic effect, antimetastasis effect and drug resistance reversal effect.
127 citations
Cites background from "A Brief Overview of the WHO Classif..."
...In addition, breast cancer is also classified based on the grade and the molecular subtypes, including luminal A, luminal B, HER2 type and triple-negative type.(4) It should be noted that the various classification parameters are not independent from one another....
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...Consequently, breast cancer has fairly complex classifications.(4,5) As of today, breast cancer is often first classified...
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...(stage 1) frequently spreads to the tissues and lymph nodes nearby (stage 2–3) or the distant organs (distant metastasis, ie, stage 4).(4) Lung, bone, liver and brain are the most Correspondence: Hui-Yi Xue; Ho-Lun wong Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA Tel +1 215 707 8173; +1 215 707 7447 Fax +1 215 707 3678; +1 215 707 3678 email ho-lun....
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References
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01 Jan 2003
2,911 citations
TL;DR: This study showed poor long-term results of the posterior bone block procedure for posterior instability and a high rate of glenohumeral osteoarthritis although three patients with post-traumatic instability were pleased with the result of their operations.
Abstract: J Bone Joint Surg [Br] 2010;92-B:651-5. Received 30 September 2009; Accepted after revision 26 January 2010 We present the long-term outcome, at a median of 18 years (12.8 to 23.5) of open posterior bone block stabilisation for recurrent posterior instability of the shoulder in a heterogenous group of 11 patients previously reported on in 2001 at a median follow-up of six years. We found that five (45%) would not have chosen the operation again, and that four (36%) had further posterior dislocation. Clinical outcome was significantly worse after 18 years than after six years of follow-up (median Rowe score of 60 versus 90 (p = 0.027)). The median Western Ontario Shoulder Index was 60% (37% to 100%) at 18 years’ follow-up, which is a moderate score. At the time of surgery four (36%) had glenohumeral radiological osteoarthritis, which was present in all after 18 years. This study showed poor long-term results of the posterior bone block procedure for posterior instability and a high rate of glenohumeral osteoarthritis although three patients with post-traumatic instability were pleased with the result of their operations.
1,329 citations
01 Jan 2010
937 citations
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...New York, Springer, 2010....
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TL;DR: The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk.
Abstract: A total of 10,542 breast biopsy specimens obtained between 1950 and 1968 were studied. Examples of atypical "ductal" (ADH) and atypical lobular hyperplasia (ALH), defined as having only some features of carcinoma in situ (CIS), were diagnosed in 3.6% of these specimens. In the same series, CIS was diagnosed in 1.7% of biopsy specimens excluding those with invasive cancer. The subsequent risk of invasive breast carcinoma after ALH or ADH was 4-5 times that of the general population. Follow-up was 90% successful and extended 17 years after biopsy. History of breast cancer in a mother, sister, or daughter doubled the risk of subsequent invasive carcinoma development (to 8 times for ALH and 10 times for ADH). The authors conclude that among the epithelial hyperplastic lesions of the human breast, a minority may be recognized by their resemblance to CIS which have a clinically significant elevation of subsequent breast cancer risk. This risk is one-half that of CIS.
894 citations