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Jacob P. Laubach, Constantine S. Mitsiades, Anuj Mahindra, Robert L. Schlossman, Teru Hideshima, Dharminder Chauhan, Nicole A. Carreau, Irene M. Ghobrial, Noopur Raje, Nikhil C. Munshi, Kenneth C. Anderson, and Paul G. Richardson

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by aberrant expansion of plasma cells within bone marrow and extramedullary sites. In 2009, 20,580 new cases of MM and 10,580 deaths from the disease occurred in the United States. Treatment traditionally consists of systemic chemotherapy, with adjunctive use of radiation or surgery in selected cases associated with extramedullary disease. The therapeutic landscape in MM has changed markedly in the past decade with the introduction of the novel immunomodulatory agents thalidomide and lenalidomide, and the first-in-class proteasome inhibitor bortezomib. Although MM remains an incurable malignancy, new approaches to therapy incorporating these agents have produced significantly higher response rates and improved intervals of both progression-free and overall survival in the context of randomized, controlled trials. In aggregate, the use of novel therapies in MM has been associated with substantial improvements in patient outcome.

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Andrew H. Ko and Margaret A. Tempero

Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a “fixed-dose rate” infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.

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Steven M. Blum, William R. Jeck, Lindsay Kipnis, Ronald Bleday, Jonathan A. Nowak, and Matthew B. Yurgelun

Two major molecular pathways of colorectal carcinogenesis, chromosomal instability (CIN) and microsatellite instability (MSI), are considered to be mutually exclusive. Distinguishing CIN from MSI-high tumors has considerable therapeutic implications, because patients with MSI-high tumors can derive considerable benefit from immune checkpoint inhibitors, and tumors that evolved through the CIN pathway do not respond to these agents. Familial adenomatous polyposis (FAP) is a genetic syndrome that is defined by a mutation in the APC gene and is thought to lead to carcinogenesis through the CIN pathway. Here, we report a case of a young woman with FAP who was treated for medulloblastoma as a child and developed advanced MSI-high colon cancer as a young adult. Her response to second-line immunotherapy enabled resection of her colon cancer, and she is free of disease >10 months after surgery. This case highlights the potential for overlap between the CIN and MSI carcinogenic pathways and associated therapeutic implications.

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Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Breast cancer is the most commonly diagnosed cancer in American women, with an estimated 214,640 cases and 41,430 deaths occurring in 2006. Estimating breast cancer risk for individual women is difficult, and most breast cancers are not attributable to risk factors other than female gender and increased age. Developing effective strategies for reducing breast cancer incidence is also difficult because few existing risk factors are modifiable and some potentially modifiable risk factors have social implications. Nevertheless, effective breast cancer risk reduction agents and strategies, such as tamoxifen, raloxifene, and risk reduction surgery, have been identified. These guidelines were developed to help women at increased risk for breast cancer and their physicians apply individualized strategies to reduce breast cancer risk.

For the most recent version of the guidelines, please visit NCCN.org

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Therese B. Bevers

The 1998 approval of tamoxifen for breast cancer risk reduction opened the era of breast cancer chemoprevention. Women at increased risk for breast cancer now had an option other than healthy lifestyle and prophylactic surgery to reduce risk. However, women and their physicians were reluctant to use tamoxifen because of associated risks. Several trials investigating raloxifene suggested it may reduce breast cancer risk without having an apparent effect on the endometrium. The Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer trial opened in 1999 to directly compare raloxifene to tamoxifen for breast cancer risk reduction. Since the unblinding of the STAR trial in 2006, raloxifene has emerged as an option for reducing breast cancer risk for postmenopausal women at increased risk for the disease.

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Mary K. Hayes, Mayra Frau, Erica Bloomquist, and Heather Wright

Background: Accurate axillary lymph node (LN) staging impacts prognosis and treatment. Breast surgeons use pre- and post neoadjuvant chemotherapy (NACT) findings to plan extent of axillary LN surgery. NACT confers an excellent treatment response in

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Adam C. Powell, Christopher T Lugo, Jeremy T Pickerell, James W Long, Bryan A Loy, and Amin J Mirhadi

Background : In the 1990s, it was demonstrated that Black patients were less likely to receive lung surgery for the treatment of Stage 1 lung cancer than White patients, and that Black patients were treated with greater delay. We examined

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Rodger J. Winn

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Christopher E. Desch

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Michael S. Sabel and Sandra L. Wong

Edited by Kerrin G. Robinson

When making a new diagnosis of melanoma, clinicians often obtain imaging studies to rule out clinically occult distant disease. These studies range from inexpensive tests, such as chest radiographs, to more expensive studies, such as PET/CT. The impetus for ordering these studies is usually the desire to identify potentially resectable distant disease, avoid surgery when curative resection is not possible, and assuage patient anxiety by showing that no evidence of distant disease is present. However, some detrimental aspects to these studies are less apparent, including cost and potential for false-positive findings. Although routine use seems reasonable, the true benefit of these studies depends on the probability of clinically occult disease being present, likelihood that disease will be detected with the available technology, and impact of earlier detection on outcome. Contrary to current practice patterns, available evidence suggests that preoperative imaging studies are associated with significant costs and minimal benefit in most patients with melanoma. This article reviews available literature on the role of pretreatment imaging in patients with newly diagnosed cutaneous melanoma.