Breast Cancer Metastasis and Drug Resistance

Aamir AhmadEditor

Breast Cancer Metastasisand Drug Resistance

Progress and Prospects

123

EditorAamir AhmadSchool of MedicineKarmanos Cancer InstituteWayne State UniversityDetroit, MIUSA

ISBN 978-1-4614-5646-9 ISBN 978-1-4614-5647-6 (eBook)DOI 10.1007/978-1-4614-5647-6Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012952583

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Preface

Breast cancer is a deadly disease that continues to disrupt the lives of millions ofwomen and their families worldwide, and it is the second leading cause of cancer-related deaths in women in the United States. Breast cancer affects one in eightwomen in the United States. These statistics are frightening despite decades ofinnovative research that led to the development of newer targeted therapies. Thisbook attempts to comprehensively summarize breast cancer as a disease, thefactors that make it particularly lethal, and the current state of breast cancerresearch. The contents are broadly divided into five informal sections as outlinedin the next few paragraphs.

One factor that particularly makes breast cancer deadly is the enormous heter-ogeneity associated with it. Cell surface receptors, such as estrogen receptor (ER),progesterone receptor (PR), or HER2/neu (ErbB2) receptor, have been targeted fortherapeutic intervention in breast cancers with significant success. However, eventhis highly successful targeted approach has not been useful for treating ‘all’ breastcancers, especially those that are negative for these receptors, the triple-negativebreast cancers. Chapters 1 through 6 form the first section of this book. Thesechapters introduce readers to the most up-to-date statistics (Chap. 1) and epidemi-ological data (Chap. 2) on breast cancer; summarize our current understanding ofracial disparity in breast cancer (Chap. 3); introduce the signaling pathways beingpursued (Chap. 4); comment on the heterogeneity in breast cancer (Chap. 5) and alsobrief the readers on the challenges posed by triple-negative breast cancers (Chap. 6).

Not much is known about the factors that may predispose individuals to breastcancer and this has also resulted in debate on the models systems to be evaluated inmodern day breast cancer research. The second section in this book, Chaps. 7through 10, touches upon some of these topics. Included in this section is a chapterthat links obesity and diabetes to breast cancer (Chap. 7), followed by a chapterthat discusses the clinical and pathological progression of early breast cancer intoan invasive disease (Chap. 8). The final two chapters in this section summarize themodels available to breast cancer researchers (Chap. 9) and also introduce readersto the state-of-the-art 4-dimensional culture models that have been proposedrecently (Chap. 10).

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Although the rate of mortality from breast cancer has decreased in developedcountries, the incidence of breast cancer has actually risen, all due to earlydetection. It is estimated that more than 90 % cancer-related deaths are due,directly or indirectly, to cancer metastasis. Bone is one of the earliest and mostcommon sites of breast cancer metastasis. Breast cancer metastasizes to bones inapproximately 70–80 % of patients with advanced disease, and similarly brainmetastasis of breast cancer is also a very challenging clinical problem. It isbelieved that 20–40 % of all patients with metastatic cancer end up with brainmetastases. We cover these topics in the third section of this book (Chaps. 11, 12).These chapters provide detailed information on our current understanding of theprocesses of bone (Chap. 11) and brain (Chap. 12) metastases of breast cancer.

In addition to metastatic disease, drug resistance is a major concern forresearchers and clinicians, because it is a big hindrance in the successfulmanagement of cancer patients. A number of targeted therapies are available forcancer subtypes that are marked by the expression of ER, PR, and overexpression ofHER2. Some cancers do not respond to the therapy at all, right from the beginning,and others eventually develop resistance to the targeted therapy. Breast cancers thathave acquired drug resistance are usually far more aggressive and difficult to treat.Section 4 of this book, Chaps. 13 through 15, deals with this clinical problemassociated with breast cancer. Here, readers are first introduced to clinical problemsassociated with the resistance to taxanes and anthracyclines in invasive breastcancers (Chap. 13); followed by the problems and current research on tamoxifenresistance in ER expressing breast cancers (Chap. 14), and finally we discuss theresistance mechanisms in HER2 overexpressing breast cancers (Chap. 15).

With a better understanding of breast cancer as a disease and the various chal-lenges it poses, as detailed in the first four sections of this book, we finally showcasethe current state of breast cancer research in Sect. 5 (Chaps. 16 through 22). We lookat the novel molecular targets/signaling pathways being pursued, and also presentthe cutting edge approaches to better understand and tackle this disease. We startwith a look at some promising novel chemical compounds for therapy (Chap. 16),and then summarize our understanding of Notch signaling pathway in breast cancer(Chap. 17). The next two chapters introduce readers to systems biology approach(Chap. 18) and epigenetics approach (Chap. 19), the two upcoming areas of breastcancer research. We round off by discussing the current understanding of cancerstem cells and miRNAs in breast cancer progression and therapeutics. Chapter 20introduces readers to these two exciting areas of research, and finally readers arebriefed on the therapeutic potential of cancer stem cells (Chap. 21) and miRNAs(Chap. 22) with particular note on how these fields of breast cancer research haveadvanced in last few years.

It is an honor to be able to work with the experts and leading scientists inindividual fields, and be able to compile this very comprehensive volume detailingalmost all the aspects of current breast cancer research. I take this opportunity tothank all the authors who, selflessly, worked hard and contributed their knowledgeto this book. My special thanks to the publisher, Springer, for entrusting me withthis project, with special mention of Fiona Sarne, the editor at the publishing office

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for helping me in every way possible. Finally, I cannot thank enough my wifeHuma and daughter Nuha for their unconditional love and support throughout.

It is my pleasure to present this volume to the scientific community for a betterunderstanding of breast cancer. I hope this will help spark new ideas and inno-vative research for the benefit of scores of patients dealing with this deadlydisease.

Aamir Ahmad

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Contents

1 Breast Cancer Statistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Jiemin Ma and Ahmedin Jemal

2 Epidemiology of Breast Cancer in Women . . . . . . . . . . . . . . . . . 19Steven S. Coughlin and Yasmin Cypel

3 The Complexities of Racial Disparity in Breast Cancer . . . . . . . . 35Joy Tang, Aamir Ahmad and Fazlul H. Sarkar

4 Major Signaling Pathways Involved in Breast Cancer . . . . . . . . . 47Saba Wasim Aziz and Moammir Hasan Aziz

5 Breast Cancer Heterogeneity in Primaryand Metastatic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65Jodi M. Saunus, Amy McCart-Reed, Majid Momeny,Margaret Cummings and Sunil R. Lakhani

6 Understanding Triple-Negative Breast Cancer . . . . . . . . . . . . . . . 97Ayca Gucalp and Tiffany A. Traina

7 The Biology of the Deadly Love Connection Between Obesity,Diabetes, and Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Bin Bao, Anthony Oraha, Aamir Ahmad, Shadan Ali, Yiwei Li,Asfar S. Azmi, Sanjeev Banerjee and Fazlul H. Sarkar

8 Progression of Early Breast Cancer to an Invasive Phenotype . . . 143Connor D. MacMillan, Ann F. Chambers and Alan B. Tuck

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9 Pre-Clinical Modeling of Breast Cancer:Which Model to Choose? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161Claire Nash and Valerie Speirs

10 Modeling Breast Cancer Progression in 4-D . . . . . . . . . . . . . . . . 177Mansoureh Sameni, Stefanie R. Mullins, Kamiar Moin,Bonnie F. Sloane and Kingsley Osuala

11 Bone Metastasis of Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . 189Takae M. Brewer, Richard L. Theriault and Naoto T. Ueno

12 Cellular and Molecular Mechanisms Involved in Breachingof the Blood–Brain Barrier by Circulating Breast Cancer Cells . . . 211Hava Karsenty Avraham, Shuxian Jiang, Lili Wang,Yigong Fu and Shalom Avraham

13 Resistance to Anthracyclines and Taxanes in Breast Cancer . . . . 227Derek Edwardson, Simon Chewchuk and Amadeo M. Parissenti

14 Understanding Tamoxifen Resistance of Breast CancerBased on Integrative Bioinformatics Approaches . . . . . . . . . . . . . 249Y. Dai and L. Huang

15 Current Understanding of Drug Resistance Mechanismsand Therapeutic Targets in HER2 OverexpressingBreast Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261Aamir Ahmad and Fazlul H. Sarkar

16 Platinum and Ruthenium Complexes for the Therapyof Breast Cancer Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275Bernhard Biersack and Rainer Schobert

17 Development of Notch Pathway Inhibitorsfor Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291Ingrid Espinoza and Lucio Miele

18 Systems Biology Approaches in Breast Cancer Studies. . . . . . . . . 329Zhiwei Wang, Shavali Shaik, Hiroyuki Inuzuka and Wenyi Wei

19 Epigenetic Factors in Breast Cancer Progression . . . . . . . . . . . . . 341Samriddhi Shukla and Syed Musthapa Meeran

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20 Breast Cancer Stem Cells and miRNAs . . . . . . . . . . . . . . . . . . . . 367Saurabh Singh

21 Breast Cancer Stem Cells: Responsible for TherapeuticResistance and Relapse? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 385Hasan Korkaya and Fayaz Malik

22 MicroRNAs in Breast Cancer Research:Progress and Promise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399Alia Ahmed, Ashhar S. Ali, Shadan Ali, Aamir Ahmad,Philip A. Philip and Fazlul H. Sarkar

23 Erratum to: Bone Metastasis of Breast Cancer . . . . . . . . . . . . . E1Takae M. Brewer, Richard L. Theriault and Naoto T. Ueno

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