Breast cancer stem cells

Breast cancer stem cells (BCSCs) constitute a subpopulation of tumor cells that express stem cell-associated markers and have a high capacity for tumor generation in vivo. Identification of BCSCs from tumor samples or breast cancer cell lines has been based mainly on CD44(+)/CD24(-/low) or ALDH(+) phenotypes. BCSCs isolation has allowed the analysis of the molecular mechanisms involved in their origin, self-renewal, differentiation into tumor cells, resistance to radiation therapy and chemotherapy, and invasiveness and metastatic ability. Molecular genetic analysis using knockout animals and inducible transgenics has identified NF-κB, c-Jun, p21(CIP1), and Forkhead-like-protein Dach1 involvement in BCSC expansion and fate. Clinical analyses of BCSCs in breast tumors have found a correlation between the proportion of BCSCs and poor prognosis. Therefore, new therapies that specifically target BCSCs are an urgent need. We summarize recent evidence that partially explain the biological characteristics of BCSCs.     

Breast cancer gene discovery

Many important advances have been made in the past decade in understanding breast cancer at the molecular level, and two important high-penetrance breast cancer genes--BRCA1 and BRCA2--have been identified. However, germline mutations in these two genes are responsible for only a minority (approximately 5%) of all breast carcinomas, and the genes responsible for the majority of breast cancer cases remain to be identified. There is evidence that there are additional high-to-moderate-penetrance breast cancer susceptibility genes but, given the high degree of molecular heterogeneity in breast carcinomas, it is likely that each of these genes is responsible for only a subset of cases. There are also many candidate low-penetrance breast cancer genes and many more are likely to be identified. In addition to germline, and somatic, sequence alterations, epigenetic changes in many genes are likely to play an important role in the pathobiology of breast cancer. Recently developed genomic technologies and the completion of the human genome sequence provide us with powerful tools to identify novel candidate breast cancer genes that could play an important role in breast tumourigenesis.     

Breast cancer in Poland syndrome

A 33-year-old African-American woman with a severe manifestation of Poland syndrome developed breast cancer in the ipsilateral breast. She had a severely hypoplastic upper extremity, including symbrachydactyly, and a hypoplastic forearm and upper arm. In addition, she lacked the sternal origin of the pectoralis muscle. She had a very small nipple-areola complex and no axillary hair. This is the first case report of breast cancer developing in the ipsilateral breast of a patient with Poland syndrome.     

Breast reconstruction after breast cancer

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Describe the mental, emotional, and physical benefits of reconstruction in breast cancer patients. 2. Compare the most common techniques of reconstruction in patients and detail benefits and risks associated with each. 3. Outline different methods of reconstruction and identify the method considered best for the patient based on timing of the procedures, body type, adjuvant therapies, and other coexisting conditions. 4. Distinguish between some of the different flaps that can be considered for autologous reconstruction. SUMMARY: Breast cancer is unfortunately a common disease affecting millions of women, often at a relatively young age. Reconstruction following mastectomy offers women an opportunity to mollify some of the emotional and aesthetic effects of this devastating disease. Although varying techniques of alloplastic and autologous techniques are available, all strive to achieve the same goal: the satisfactory reformation of a breast mound that appears as natural as possible without clothing and at the very least is normal in appearance under clothing. This article summarizes the various approaches to breast reconstruction and offers a balanced view of the risks and benefits of each, all of which in the end offer the opportunity for excellent and predictable results with a high degree of patient satisfaction.     

Breast cancer and the environment

The most recent estimate of the overall worldwide burden of cancer is that in the year 2000 more than 10 million new cancer cases occurred and approximately 6 million cancer deaths. Breast cancer accounts for about 1 in 10 cancers and is the most frequent cancer affecting women. Since 10% of all cancers in the world are breast cancer (only affecting half of the population as breast cancer almost exclusively concerns only women), it is being considered an epidemic. In terms of the absolute number of incident cases, breast cancer now ranks first not only in the industrialized world but also in the developing world. The worldwide mortality figure for the year 2000 was 370,000. However, there are marked geographical differences, with Africa and Asia currently having incidence rates some 10 times lower than those of North America and northern Europe. Studies of migrant populations have long indicated that the genetic background only plays a tiny, if any, role in these differences. Over time, clear increases have been seen in the global number of cases: from 572,000 in 1980 to 1,050,000 in 2000. This corresponds not only to a modest increase in incidence rates in countries with a long history of frequent breast cancer but also to marked increases in countries with previously low rates. The reasons for these increases are currently unexplained and a possible hypothesis relates to environmental factors. By contrast, in a number of countries in the western world mortality rates are stable, and, in the USA and the United Kingdom, even decreasing slightly. The aetiology of breast cancer has been the subject of hundreds of studies since the pioneering investigation of Lane Claypon in 1926. Risk factors belong to different domains: reproductive life, hormonal factors, diet, genetics (BRCA1, BRCA2) and exposure to radiation and selected chemicals. Yet, much breast cancer remains unexplained and new aetiological links must be sought such as occupational factors and exposure to pesticides and other endocrine disrupters. A recent international summit on breast cancer and the environment outlined the need for more research to be conducted into the effects of exposure in the vicinity of nuclear power plants or chemical landfill sites and, more generally, into contaminants in food, air, water and soil. This is particularly relevant in some parts of the world such as Africa.