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HER2 Testing in Breast Cancer: NCCN Task Force Report and Recommendations

Robert W. Carlson, Susan J. Moench, M. Elizabeth H. Hammond, Edith A. Perez, Harold J. Burstein, D. Craig Allred, Charles L. Vogel, Lori J. Goldstein, George Somlo, William J. Gradishar, Clifford A. Hudis, Mohammad Jahanzeb, Azadeh Stark, Antonio C. Wolff, Michael F. Press, Eric P. Winer, Soonmyung Paik, Britt-Marie Ljung, and for the NCCN HER2 Testing in Breast Cancer Task Force

NSABP B-31 and NCCTG N9831 trials of adjuvant therapy in breast cancer. From Romond et al. 19 ; with permission. HER2 Testing: Summary of Clinical Issues The use of HER2 tumor biomarker status in clinical decision-making ( Figure 1 ) has been limited by

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Controversies in the Surgical Management of Gastric Cancer

David A. Kooby and Daniel G. Coit

Although the incidence of gastric adenocarcinoma in the United States has declined steadily since the early 1900s, it remains a significant health problem. Progress has been made during the past few decades in several areas: Lymph node staging has been refined, perioperative mortality has fallen, and plausible adjuvant therapy has emerged. Currently, complete surgical resection is the mainstay of therapy because it is the only potentially curative option; however, considerable controversy remains regarding the specifics of a surgical approach. This article examines 4 major controversies in the management of gastric cancer: extent of gastric resection, role of extended lymph node dissection, value of elective splenectomy for proximal gastric lesions, and current state of adjuvant therapy. Pertinent retrospective and prospective studies are reviewed to help formulate meaningful conclusions.

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Liver Transplantation for Hepatocellular Carcinoma: An Update

Jean F. Botha and Alan N. Langnas

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and the most common primary hepatic malignancy. It arises on a background of hepatic cirrhosis in approximately 95% of the cases in the United States. A wide variety of treatment modalities have been applied in the treatment of HCC. Liver transplantation has emerged as the preferred treatment for patients with small HCC. Transplantation for patients whose tumors do not exceed the Milan criteria yields results equivalent to those of transplantation for non-HCC indications. Controversy now exists regarding the use of living donors, expansion of selection criteria, and role of adjuvant therapy.

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Biologics in Cervical Cancer Therapy

Lyndsay J. Willmott, Daniele A. Sumner, and Bradley J. Monk

Though cervical cancer incidence and prevalence have decreased in the United States, the disease remains a very important cause of morbidity and mortality worldwide. Current therapy for early-stage disease is surgical with adjuvant therapy being administered according to histopathologic findings. Pelvic radiation with concomitant platinum-based chemotherapy is used to treat locally advanced disease, whereas metastatic and recurrent lesions continue to be difficult to effectively treat and cure. Clinical trials in this latter scenario have suggested that clinical benefit may be associated with biologic therapies. This article focuses on the use of targeted therapies in cervical cancer, specifically evaluating antiangiogenesis and endothelial growth factor receptor–related treatments.

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Bone Mineral Density Testing Disparities Among Patients With Breast Cancer Prescribed Aromatase Inhibitors

John Charlson, Elizabeth C. Smith, Alicia J. Smallwood, Purushottam W. Laud, and Joan M. Neuner

Objectives: Aromatase inhibitors (AIs) are standard adjuvant therapy for postmenopausal women with early-stage, estrogen receptor–positive breast cancer. We designed our study to determine whether women initiating adjuvant therapy with an AI underwent baseline bone mineral density testing, as well as what factors predicted adherence with testing guidelines. Methods: Medicare Parts A, B, and D claims were used to identify a cohort of women aged 67 years and older with incident breast cancer in 2006 and 2007 who started AI therapy. Medicare claims provided information about bone density testing, as well as demographic and other treatment data through 2012. We also ascertained which patients were treated with bisphosphonates and studied the relationship of bisphosphonate therapy with bone density testing. Results: Approximately two-thirds of patients had baseline bone density testing. Older age, comorbidity, low income, and black race were associated with lower rates of baseline bone density testing. Testing rates decreased substantially with increasing age from 73% for women aged 67 to 70 years to 51% for those 85 years of age and older (adjusted odds ratio for not being tested, 2.48 [Cl, 2.17–2.82]). The proportion of women who had neither bone density testing nor bisphosphonate therapy increased with age as well. Conclusions: Despite the importance of age as a risk factor for fractures, older women starting treatment with AIs for treatment of breast cancer are less likely to undergo recommended bone density assessment.

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Non–Small Cell Lung Cancer

UCSF Helen Diller Family Comprehensive Cancer Center

Lung cancer is the leading cause of cancer-related death in both men and women in the United States. An estimated 213,380 new cases (114,760 men and 98,620 women) of lung and bronchus cancer will be diagnosed in 2007, and 160,390 deaths (89,510 in men, 70,880 in women) are estimated to occur because of the disease. Non-small cell lung cancer (NSCLC) accounts for 80% to 85% of all lung cancer cases and includes 3 major types: (1) adenocarcinoma; (2) squamous cell (epidermoid) carcinoma; and (3) large-cell carcinoma. Adenocarcinoma is the most common type of lung cancer seen in the United States and is also the most frequently occurring cell type in nonsmokers. Important updates to the 2008 guidelines on NSCLC include the addition of tables on drugs and dosing information on chemotherapy regimens for adjuvant therapy.

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

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Risk Reduction Strategies for Ductal Carcinoma In Situ

Adam L. Cohen and John H. Ward

Ductal carcinoma in situ (DCIS) is a premalignant condition that, if left untreated, may progress to invasive breast cancer. After lumpectomy, DCIS can recur, and about half of recurrences are invasive. In 4 randomized trials, radiation has been shown to decrease the local recurrence rate by about half, though it does not change survival. Based on the results of 3 randomized trials, tamoxifen probably decreases cancer recurrence by about 30%, particularly in young women. Low fat diets, weight loss, and physical activity decrease invasive breast cancer recurrence and may be recommended to certain women with DCIS. Prognostic factors include age, extent of DCIS, margin status, grade, and presence of necrosis, although how these affect adjuvant therapy is unclear. Research evaluating other drugs to reduce recurrence risk and on different ways of delivering radiation continues.

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Using Imatinib as Neoadjuvant Therapy in Dermatofibrosarcoma Protuberans: Potential Pluses and Minuses

Hillary Johnson-Jahangir, William Sherman, and Désirée Ratner

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.

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Role of Dermatologists in Treating Melanoma

Allan C. Halpern and Sanjay K. Mandal

Melanoma is a major focus of dermatology training and practice, with dermatologists playing a central role in managing melanoma through primary prevention, secondary prevention, diagnosis, and treatment of thinner tumors. Dermatologists have led public health efforts to raise melanoma awareness, promulgate the early warning signs of melanoma, and promote melanoma prevention through sun protection. Dermatologists have unique expertise in melanoma risk assessment and the clinical diagnosis of melanoma through visual inspection and the use of diagnostic aids, including dermoscopy and photographically assisted follow-up. Increasing incidence of melanoma, earlier melanoma detection, narrower excision margins, and improved surgical training in dermatology have recently combined to enhance the role of dermatologists in melanoma care. For patients with thin primary melanomas, dermatologists are increasingly assuming complete care, including wide local excision and long-term surveillance for both disease recurrence and detection of new primary melanoma. Conversely, the advent of sentinel lymph node biopsy and adjuvant therapy has made melanoma management more complex and has intensified the need for a multidisciplinary approach to the disease. In this context, dermatologists contribute significantly to the formation, administration, and implementation of multidisciplinary melanoma programs.

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Larotrectinib in a Patient With Advanced Pleomorphic Liposarcoma of the Uterus

Anisley Valenciaga, O. Hans Iwenofu, and Gabriel Tinoco

Pleomorphic liposarcoma of the uterus (PLU) is an extremely rare disease with poor prognosis. Limited treatment options exist for these patients, and disease recurrence usually occurs rapidly within months of initial diagnosis. Few case reports of metastatic PLU are available in the literature. We describe a 70-year-old woman who presented with a large uterus and ovarian mass on imaging and negative serum tumor markers and endometrial biopsy. Staging revealed localized disease. Surgical resection revealed PLU on pathology. Immunohistochemistry was negative for smooth muscle actin (SMA), S100, and MDM2, and positive for CD10 and cyclin-D1. She was treated with adjuvant therapy and experienced disease recurrence in the liver at 15 months from surgery. Genetic testing of the metastasis showed IQGAP-NTRK3 gene fusion. She was given entrectinib but continued to show progression in the liver. Right partial hepatectomy was performed, showing positivity for CD10, BCL-1, MDM2, and SMA on tumor staining. Treatment was switched to pazopanib with disease progression in the neck. She was treated with larotrectinib last, showing no disease progression and adequate tolerance of therapy after 18 months of this treatment. This is the first case in the literature of metastatic PLU with NRTK3 fusion treated with sequential first-generation NRTK inhibitors. More case reports are needed to identify commonalities and therapeutic options. Genetic testing in all PLU cases is needed for targeted therapy approaches.