Challenges of Intraoperative Cancer Diagnosis
Intraoperative cancer detection has been a major challenge for accurate determination of surgical margin and early diagnosis of cancers. Since only a limited number of fluorescent probes or organic dye molecules have been approved by the FDA for human use, cancer and nerve tissues are not usually distinguishable from normal tissue structures using conventional light microscopy, posing the main obstacle to the identification of different tissue types. As a result, definitive diagnosis is only accessible after tissue biopsy, sectioning, and staining, a lengthy process that is incompatible with the on-the-spot requirement of surgical interventions. In addition, clinicians have long realized that cancer represents a heterogeneous population of diverse diseases. This heterogeneity could lead to ample opportunity for subpopulations of cancer cells to evade monotherapy. Deferential diagnosis of cancer subtypes thus becomes critical to improve treatment efficacy of individualized treatment. Targeting this problem, substantial research efforts have been allocated to provide real-time diagnostic capability [1,2]. Among imaging modalities, molecular vibrational imaging methods are normally preferred, given their cellular resolution, a condition precedent to effective diagnostic judgment.
BREAST CANCER
Breast cancer is perhaps the single most important medical concern women face today. Although there has been an overall decrease in breast caner rates in the United States in recent decades, in 2007 there were greater than 180,000 new cases of invasive breast cancer and 40,910 breast cancer-related deaths. This is equivalent to a breast cancer diagnosis every 2 minutes.2 Breast cancer is the leading cause of cancer in women, accounting for one-third of all cancer cases.3 All women are affected by breast cancer—whether by literal diagnosis or a lifetime of worry about whether they will experience this disease.2 It has been estimated that 50% of all women in the United States at some point in their lives will ask their physicians about a concerning lump or other worrisome breast finding with the anxiety that they have breast cancer. Many have known a friend, relative, or colleague who has gone through a possible or actual breast cancer diagnosis.
Breast cancer, from etiology to treatment, is a vast and complex topic with an enormous literature. There is controversy over screening methods, treatments, and the role of complementary and alternative therapies in the care of women with breast cancer. There are still many unknowns in cancer diagnosis, prevention, and treatment. It would be impossible to elucidate the entire topic of breast cancer, or even that of breast cancer and CAM, within the confines of a single chapter. It is hoped that this chapter will help the reader begin to understand the magnitude of breast cancer as a disease that effects all women, whether as a direct clinical reality or a lifelong concern, to understand nonmodifiable and modifiable breast cancer risk factors, to gain perspective on the complexity of issues women must sort through regarding screening and, if diagnosed, choices regarding their treatment, including whether and how to use CAM therapies. This chapter does not provide guidelines for the botanical treatment of breast cancer, although does direct readers to additional resources on evidence for botanicals commonly used in cancer treatment protocol.
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Breast Cancer
DAVID HEBER, GEORGE BLACKBURN, in Nutritional Oncology (Second Edition), 2006
INTRODUCTION
Breast cancer is the most common form of cancer in women and is the second most common cause of cancer-related deaths among women. In fact, breast cancer accounts for 22% of all female cancers and 15% of cancer deaths among women (Edwards et al., 2002; Stewart et al., 2004). In the United States, which currently accounts for ∼20% of the one million cases occurring worldwide, there has been an increase in breast cancer incidence over the past 20 years with an overall slight decrease in mortality. Therefore, although treatment and early diagnosis has made some modest inroads, much more needs to be done in primary breast cancer prevention and prevention of breast cancer recurrence in the breast cancer survivor. Gene–nutrient interaction plays a key role in breast cancer, and the factors that influence susceptibility to breast cancer from an environmental and genetic standpoint remain poorly understood. There is an urgency to this research because there is a global trend in developing countries of an increase in breast cancer incidence as Western diets and lifestyles are spreading around the world.
The etiology of breast cancer has been studied extensively using several different but complementary approaches. Our understanding of the possible etiological factors has been obtained by considering information derived from epidemiological studies, including genetic epidemiology studies and information derived over 7 decades on the basic physiology, anatomy, and cellular signaling within the cellular matrix of breast tissue. Intraductal epithelial cells account for the vast majority of breast cancer (Russo et al., 2001). Physiological studies in animals and humans have provided a valuable framework in which to consider the etiology of breast cancer by describing the growth, differentiation, and involution of breast tissue at menopause and the critical role of the breast ductal cell microenvironment.
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Breast Cancer
Philip S. Bernard, in Genomic and Personalized Medicine (Second Edition), 2013
Introduction
Breast cancer is the most prevalent cancer in the world (~4.4 million) with a high yearly incidence (~1.15 million newly diagnosed) and relatively lower death rate (~465,000) (Parkin et al., 2005). Predicting who will develop breast cancer and who will survive breast cancer continues to be challenging for modern medicine. Even in an era in which we know the sequence of all genes (coding and non-coding), and can decipher many of the protein interactions and regulatory mechanisms, there are many unknown factors that can lead to the development, resistance, and progression of the disease.
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Breast Cancer
M. Porteous, D. Stirling, in Brenner's Encyclopedia of Genetics (Second Edition), 2013
Introduction
Breast cancer is now the commonest cancer in the United Kingdom with incidence rates in women increased by 50% over the past 25 years. General population lifetime risk for a woman of developing breast cancer is between 1 in 8 and 1 in 12. However, the bulk of this risk is skewed toward the sixth decade and beyond with age the main risk factor for the development of breast cancer. Factors such as early menarche, late menopause, postmenopausal obesity, dense breasts, and a history of benign proliferative breast disease also contribute to overall risk. The main risk factor after increasing age is a family history of breast cancer and Table 1 shows the characteristic features of familial breast cancer.
Table 1. Features of a family history suggestive of genetic predisposition to cancer
• More cancers than you would expect to see by chance.• Affected relatives are closely related and span more than one generation.• Cancers are diagnosed at an earlier age than expected for that particular cancer.• A close relative that has developed more than one primary cancer.• Relatives are affected by the same types of cancers or cancers that are part of a known cancer syndrome.• Ethnic origin in which founder mutations are recognized.
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Breast Cancer
Tieraona Low Dog MD, in Women's Health in Complementary and Integrative Medicine, 2005
Acupuncture
Acupuncture is often used by cancer patients to obtain relief from the nausea and vomiting associated with chemotherapy.112 The National Institutes of Health Consensus Development Conference on Acupuncture in 1997 stated that "there is clear evidence that needle acupuncture treatment is effective for postoperative and chemotherapy-induced nausea and vomiting, and for nausea of pregnancy and postoperative dental pain." The antiemetic effects of acupuncture may stem from an increase in hypophyseal secretion of β-endorphins and adrenocorticotrophic hormone, with subsequent inhibition of the chemoreceptor trigger zone and vomiting center. Acupuncture also affects the upper gastrointestinal tract, decreasing acid secretion and repressing gastric arrhythmias.113
A three-arm, randomized, controlled trial of 104 women (mean age 46 years) with breast cancer compared the effectiveness of electroacupuncture with minimal needling and mock electrical stimulation or antiemetic medications alone in the control of emesis among patients undergoing a highly emetogenic chemotherapy regimen. Among women receiving high-dose chemotherapy, adjunct electroacupuncture was more effective in controlling emesis than was minimal needling or antiemetic pharmacotherapy alone, although the observed effect was of limited duration.114
Some oncology centers are making the services of licensed acupuncturists available on-site, and an increasing number of managed-care organizations and insurance companies are reimbursing for treatment.
BREAST CANCER/BREAST HEALTH RESOURCES
Adapted from Conry C: Evaluation of a breast complaint: Is it cancer? Am Fam Phys 49(2):445-450, 1994.Copyright © 1994
•
Cancer Information Service of the National Cancer Institute
800-4-CANCER (toll-free)
http://cis.nci.nih.gov
•
National Institutes of Health National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse
888-644-6226 (toll-free); international 1-301-519-3153
www.nccam.nih.gov
•
National Breast Cancer Coalition
202-296-7477
www.stopbreastcancer.org
•
SHARE (Self-help for women with breast cancer)
English, 212-382-2111; Spanish, 212-719-4454
www.sharecancersupport.org
•
Y-ME National Breast Cancer Organization, Inc.
800-221-2141 (toll-free)
www.y-me.org
•
Lesbian Community Cancer Project
4753 North Broadway, Suite 602
Chicago, IL 60640
773-561-4662
www.lccp.org
•
Breast Cancer Action
1280 Columbus Ave., Suite 204
San Francisco, CA 94133
415-243-9301
www.bcaction.org
•
National Women's Health Network
202-628-7814, 202-347-1140
www.nwhn.org
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Breast Cancer
Umberto Veronesi, Peter Boyle, in International Encyclopedia of Public Health (Second Edition), 2017
Conclusions
Breast cancer is the most common type of tumor in women in most parts of the world. Although stabilized in Western countries, its incidence is increasing in other continents. Prevention of breast cancer is difficult because the causes are not well known. We know of many risk factors such as nulliparity, late age at first pregnancy, little or no breastfeeding, which, however, are linked to the historic development of human society. On the contrary, a great effort is needed to improve early detection of the tumor. Screening programs among the female population should therefore be implemented. The early discovery of a small breast carcinoma leads to a very high rate of curability and entails very mild types of treatment, with preservation of the body image. Treatments are improving, but a strict interdisciplinary approach is essential. It is conceivable that in all countries specialized centers or units for breast cancer management should be set up.
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Breast Cancer
Alireza Rezaee, ... Mohsen Beheshti, in PET/CT in Cancer: An Interdisciplinary Approach to Individualized Imaging, 2018
Abstract
Breast cancer is the most common type of invasive cancer and the second cause of cancer-related death in women. In addition to clinical information, benign findings and pitfalls in fludeoxyglucose (FDG) PET/CT reading, and teaching cases, this chapter reviews evidence-based recommendations regarding PET/CT examination in breast cancer and compares them with statements in major clinical guidelines. According to evidence-based data, FDG PET/CT can potentially replace conventional imaging modalities in staging of locally advanced breast cancer and is recommended for the evaluation of response to chemotherapy or radiation therapy. Interestingly, FDG uptake is higher in patients with triple-negative or HER2-positive malignant lesions and inversely correlates with prognosis.
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Breast cancer
Nancy M Hardy, Michael R Bishop, in Hematopoietic Stem Cell Transplantation in Clinical Practice, 2009
Introduction: background and conventional treatment options
Breast cancer is the most common cancer in women and the leading cause of cancer deaths in women worldwide. More than 1.15 million cases of breast cancer are diagnosed annually, and in 2002 there were over 410,000 deaths due to this disease.1,2 While breast cancer with limited spread is potentially curable, prognosis is heavily dependent on the degree of involvement of the axillary lymph nodes:3 nearly 100% of women without lymph node involvement (stage I/IIA) are alive 10 years after diagnosis as compared to 45–59% of those with 4–9 involved lymph nodes (stage II/III), and 68–77% with 10 or more involved lymph nodes.4 Locally advanced and inflammatory breast cancers are a heterogeneous group of tumors; as a consequence, prognosis is difficult to predict and is influenced largely by biologic characteristics of individual tumors.5 Inflammatory breast cancers are an uncommon subtype characterized by dermal lymphatic invasion, often extensive local involvement, and aggressive behavior. Even with combined modality therapy, the 5-year disease-free survival (DFS) is approximately 30%.6
Fewer than 6% of women who are diagnosed with breast cancer present with distant metastases;7 however, once there is metastatic spread, breast cancer is a chronic, virtually incurable disease, with 20% surviving 5 years, and a median survival of 2–3 years.8 The high rate of recurrence after conventional therapy in patients with stage III disease, particularly in patients with 10 or more positive axillary nodes, and the poor prognosis after metastatic spread prompted evaluation of novel forms of therapy. High-dose chemotherapy (HDT) with autologous hematopoietic stem cell (AHSC) support and cellular immunotherapy using allogeneic lymphocyte-based or vaccine-based strategies have each been employed in the treatment of breast cancer.
Breast cancer presenting with locoregional spread is conventionally treated with combined-modality therapy aimed at eliminating the primary tumor (surgery) and preventing local (radiation therapy) and metastatic (systemic therapy) recurrence. Adjuvant polychemotherapy improves DFS and overall survival (OS) in women with early breast cancer, most demonstrably in women aged less than 50 years and with use of anthracycline-containing regimens.9 Randomized, controlled trials suggest improved DFS and OS with both dose-escalated epirubicin10 and combined anthracycline-taxane10,11 regimens. Direct comparisons between these two approaches are limited, particularly for patients presenting with node-positive disease. However, an indirect comparison suggested that adjuvant therapy with six cycles of either docetaxel, doxorubicin and cyclophosphamide (TAC) or fluorouracil, epirubicin 100 mg/m2 and cyclophosphamide (FEC100) may offer survival advantages over conventionally dosed anthracycline-based therapy to this subgroup of patients.10 For patients whose tumors express estrogen and/or progesterone receptors or demonstrate in-creased expression of Her2/neu, therapy with estrogen antagonists8 and the monoclonal antibody trastuzumab,12,13 respectively, have shown DFS and OS benefits in the adjuvant setting. Conventional therapy for patients presenting with stage III breast cancer (including inflammatory breast cancer) involves aggressive treatment with neo-adjuvant chemotherapy, surgery and radiation therapy, and additional adjuvant systemic therapy.14 Recurrence rates remain high, and the ideal choice of therapeutic agents, the sequence of treatment modalities and the number of chemotherapy cycles administered remain areas of investigation, hampered by heterogeneity of the biology of locally advanced tumors.
Chemotherapy, hormonal therapy, radiotherapy, biologic therapy and limited surgery are all used in the treatment of women with metastatic breast cancer (MBC). Almost all women with MBC will eventually become refractory to hormonal therapy, necessitating the use of systemic chemotherapy. The two most active classes of chemotherapy against MBC are anthracyclines and taxanes; however, both of these are more commonly being used together as part of adjuvant therapy, potentially limiting their usefulness in the metastatic setting.15 A variety of second- and third-line chemotherapeutic agents is available, including vinorelbine, gemcitabine and capecitabine, either alone or in combination with biologic agents such as trastuzumab. Responses to these therapies are relatively consistent (15–30%), and median survival after their administration is generally less than 24 months.16 While aggressive treatment strategies for local disease have resulted in reduced recurrence rates, particularly in tumors with histologic or genetic features suggestive of a poor prognosis, the prognosis for women with metastatic disease has changed comparatively little, in spite of a steady stream of new cytotoxic and biologic agents with breast cancer activity.17 This failure has prompted continued search for alternative treatment paradigms to more effectively control advanced breast cancer.
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Breast Cancer
Paul K. Marcom, in Genomic and Precision Medicine (Third Edition), 2017
Abstract
Personalized breast cancer care has been greatly advanced by developments in genetics and genomics. Precision medicine approaches have led to a reduction in breast cancer mortality, while also decreasing morbidity from treatment. The advent of next-generation sequencing now allows for testing of a larger panel of germline mutations predisposing to breast cancer. This capacity has led to detection of changes sometimes of uncertain significance, and without clear clinical guidelines. However, germline testing results are now translating into tools for guiding therapy as well as assessing genetic risk. Early-stage breast cancer management is primarily guided by conventional markers such as estrogen receptor, progesterone receptor, and HER-2 amplification status; however, it is also increasingly guided by molecular classification, and gene expression profiling that provides prognostic and predictive information. For advanced, metastatic disease, detection of gene mutations also promises to guide therapy more precisely, although this concept is still very much in development.
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