Antineoplastics, Alkylating
Alkylating agents constitute one of the earliest classes of antineoplastic agents used to treat cancer. They work by cross-linking DNA, which impedes cellular growth. They can be used alone or in combination with other chemotherapeutic agents.
Carboplatin
Carboplatin is an analogue of cisplatin. It is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing the SH group. Cytotoxicity can occur at any stage of the cell cycle, but the cell is most vulnerable to the action of these drugs in the G1 and S phases.
Carboplatin has the same efficacy as cisplatin but a better toxicity profile. Its main advantages over cisplatin include less nephrotoxicity and ototoxicity, absence of a need for extensive prehydration, and reduced likelihood of inducing nausea and vomiting; however, it is more likely to induce myelotoxicity.
Cyclophosphamide (Cytoxan)
Cyclophosphamide is chemically related to nitrogen mustards. It can be used as a single agent or in various combination chemotherapy regimens for recurrent or metastatic breast cancer.
Cyclophosphamide is activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type of reaction. The mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
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Anatomy of the breast.
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Intrinsic subtypes of breast cancer.
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Breast cancer. Intraductal carcinoma, comedo type. Distended duct with intact basement membrane and central tumor necrosis.
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Breast cancer. Intraductal carcinoma, noncomedo type. Distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern.
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Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
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Breast cancer. Lobular carcinoma in situ. Enlargement and expansion of lobule with monotonous population of neoplastic cells.
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Breast cancer. Infiltrating ductal carcinoma. Low-grade carcinoma with well-developed glands invading fibrous stroma.
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Breast cancer. Colloid (mucinous) carcinoma. Nests of tumor cells in pool of extracellular mucin.
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Breast cancer. Papillary carcinoma. Solid papillary growth pattern with early cribriform and well-developed thin papillary fronds.
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Anatomy of the breast. Courtesy of Wikimedia Commons (Patrick J Lynch, medical illustrator).
Tables
Pavani Chalasani, MD, MPH Assistant Professor of Medicine, Section of Hematology/Oncology, Department of Medicine, Arizona Health Sciences Center, University of Arizona College of Medicine
Pavani Chalasani, MD, MPH is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Hemostasis and Thrombosis Research Society, SWOG
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bayer, Heron, Amgen, Athenex, Novartis, Eisai<br/>Received research grant from: Pfizer.
John V Kiluk, MD, FACS Associate Professor, Department of Oncologic Sciences, Department of Surgery (Joint Appointment), University of South Florida Morsani College of Medicine; Clinical Director, Breast Surgical Oncology, Associate Member, Comprehensive Breast Program, Department of Women's Oncology, H Lee Moffitt Cancer Center and Research Institute
John V Kiluk, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, Moretz Surgical Society, Society of Surgical Oncology, Southeastern Surgical Congress
Disclosure: Nothing to disclose.
Alison T Stopeck, MD Professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center; Director of Clinical Breast Cancer Program, Arizona Cancer Center; Medical Director of Coagulation Laboratory, University Medical Center; Director of Arizona Hemophilia and Thrombosis Center
Alison T Stopeck, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology, SWOG, American Society of Clinical Oncology, Hemophilia and Thrombosis Research Society
Disclosure: Received honoraria from Genentech for speaking and teaching; Received honoraria from AstraZeneca for speaking and teaching; Received grant/research funds from AstraZeneca for other.
Patricia A Thompson, PhD Assistant Professor, Department of Pathology, University of Arizona College of Medicine
Disclosure: Nothing to disclose.
Kathy D Miller, MD Professor of Medicine, Indiana University School of Medicine; Co-Director, Breast Cancer Program, Indiana University Simon Cancer Center
Kathy D Miller, MD is a member of the following medical societies: American Association for Cancer Research, European Society for Medical Oncology, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, Hoosier Cancer Research Network, Indiana Oncology Society
Disclosure: Nothing to disclose.
Leona Downey, MD Assistant Professor of Internal Medicine, Section of Oncology and Hematology, University of Arizona, Arizona Cancer Center
Leona Downey, MD is a member of the following medical societies: American Geriatrics Society, American Society of Clinical Oncology, and Southwest Oncology Group
Disclosure: Nothing to disclose.
Manjit Singh Gohel, MD, MRCS, MB, ChB Specialist Registrar, Division of Breast and Endocrine Surgery, Northwick Park Hospital
Disclosure: Nothing to disclose.
Harold Harvey, MD Professor, Department of Medicine, Pennsylvania State University
Disclosure: Nothing to disclose.
Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed) Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India
Disclosure: Nothing to disclose.
Julie Lang, MD Assistant Professor of Surgery and the BIO5 Institute, Director of Breast Surgical Oncology, University of Arizona College of Medicine
Julie Lang, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Clinical Oncology, Association for Academic Surgery, and Society of Surgical Oncology
Disclosure: Genomic Health Grant/research funds Speaking and teaching; Agendia Grant/research funds Speaking and teaching; Surgical Tools Grant/research funds Research; Sysmex Grant/research funds Research
Robert B Livingston, MD Professor of Clinical Medicine and Director, Clinical Research Shared Services, Arizona Cancer Center
Robert B Livingston, MD is a member of the following medical societies: American Association for Cancer Research, American Federation for Clinical Research, and American Society of Clinical Oncology
Disclosure: Nothing to disclose.
Hanan Makhoul, MD Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine
Disclosure: Nothing to disclose.
Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences
Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.
Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International
Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy
Disclosure: Nothing to disclose.
Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK
Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.
Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center
Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine
Disclosure: Nothing to disclose.
Wiley Souba, MD Chairman, Professor, Department of General Surgery, Pennsylvania State College of Medicine; Chief Surgeon, The Milton S Hershey Medical Center
Disclosure: Nothing to disclose.
Rachel Swart, MD, PhD Assistant Professor of Medicine, Department of Hematology and Oncology, Arizona Cancer Center, University of Arizona
Rachel Swart, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Arizona Medical Association, and Southwest Oncology Group
Disclosure: Roche Grant/research funds Other
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Simon Thomson, MB, BCh, MD, FRCS Specialist Registrar, Department of Breast and Endocrine Surgery, Northwick Park Hospital, UK
Simon Thomson, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association
Disclosure: Nothing to disclose.