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Jennifer A. Ligibel

Growing evidence suggests that physical activity may be an important part of survivorship care for women with a history of breast cancer. Observational evidence suggests that women who are physically active after breast cancer diagnosis have a 30% to 50% lower risk of breast cancer recurrence, breast cancer death, and overall death compared with sedentary individuals. Although randomized controlled trials have not been performed to test the ability of exercise to improve outcomes in women with early-stage breast cancer, many small intervention studies have shown the safety and potential benefits of exercise in the adjuvant and posttreatment settings. These studies have shown that physical activity can be performed safely both during and after adjuvant treatment for breast cancer, and that women who increase physical activity in these settings experience improvements in fitness, strength, quality of life, and other end points. Although more research is needed to fully define the role of exercise in breast cancer survivors, the many proven benefits of physical activity have led the American Cancer Society and American College of Sports Medicine to encourage regular participation in moderate-intensity recreational activity for most breast cancer survivors. This article reviews the growing evidence that exercise could be an important part of breast cancer survivorship, and describes current exercise guidelines for breast cancer survivors.

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Jennifer A. Ligibel and Eric P. Winer

Adjuvant hormonal therapy has been shown to decrease the risk of breast cancer recurrence and overall mortality in patients with hormone receptor-positive breast cancer. Tamoxifen has been used in this setting for many years, both in premenopausal and postmenopausal patients. Tamoxifen is not devoid of toxicity, and attempts have been made to develop newer hormonal agents with better efficacy and less toxicity. The aromatase inhibitors have shown equivalent or superior efficacy to tamoxifen in the treatment of metastatic breast cancer, and efforts are underway to determine the role of these agents in early breast cancer. The ATAC trial recently showed that use of the third-generation aromatase inhibitor anastrozole in the adjuvant setting led to a modest improvement in relapse-free survival as compared with tamoxifen. Patients treated with anastrozole were also less likely to develop uterine cancer or experience a thromboembolic event. However, patients treated with anastrozole were more likely than those treated with tamoxifen to suffer a fracture or other musculosketal problem. An ASCO technology assessment panel reviewed the relevant data and issued a consensus statement regarding the use of aromatase inhibitors in the adjuvant setting. In general, the panel favored the continued use of tamoxifen as adjuvant hormonal therapy for most postmenopausal women. Within the next few years, further data from the ATAC trial and from other trials of aromatase inhibitors in the adjuvant setting should be available to guide treatment recommendations for this patient population.

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Jennifer A. Ligibel and Crystal S. Denlinger

Survivorship is a stage in the cancer journey like diagnosis and treatment, but it tends to be somewhat neglected in the quiet afterthoughts of treatment completion. Although cancer recurrence, second cancers, and late side effects of treatment are major concerns for survivors, survivors also may experience a variety of long-term physical and psychological sequelae of a cancer diagnosis and treatment. Oncology professionals may be ill-prepared to tackle these topics, and they have few guidelines for meeting these patient needs. In this article, Dr. Jennifer A. Ligibel and Dr. Crystal S. Denlinger present highlights from the inaugural NCCN Clinical Practice Guidelines in Oncology on survivorship care, focusing on the subtopics of exercise, cognitive function, immunization, and sexual function. They also discuss implementing new recommendations on survivorship assessment in the clinic.

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Ann M. Berger, Amy Pickar Abernethy, Ashley Atkinson, Andrea M. Barsevick, William S. Breitbart, David Cella, Bernadine Cimprich, Charles Cleeland, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Phyllis Kaldor, Jennifer A. Ligibel, Barbara A. Murphy, Tracey O'Connor, William F. Pirl, Eve Rodler, Hope S. Rugo, Jay Thomas and Lynne I. Wagner

Overview Fatigue is a common symptom in patients with cancer and is nearly universal in those undergoing cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biologic response modifiers.1–10 The symptom is experienced by 70% to 100% of patients with cancer who undergo multi-modal treatments and dose–dense, dose-intense protocols.11 In patients with metastatic disease, the prevalence of cancer-related fatigue exceeds 75%. Cancer survivors report that fatigue is a disruptive symptom months or even years after treatment ends.12–21 The distinction between tiredness, fatigue, and exhaustion has not been made, despite conceptual differences.22,23 Patients perceive fatigue to be the most distressing symptom associated with cancer and its treatment, more distressing even than pain or nausea and vomiting, which, for most patients, can generally be managed with medications.24,25 Fatigue in patients with cancer has been underreported, underdiagnosed, and undertreated. Persistent cancer-related fatigue affects quality of life (QOL), because patients become too tired to fully participate in the roles and activities that make their lives meaningful.16,26–28 Health care professionals have been challenged in their efforts to help patients manage this distressful symptom and remain as fully engaged in life as possible. Because of the successes in cancer treatment, health care professionals are now likely to see patients with prolonged states of fatigue related to the late effects of treatment. Disability-related issues are relevant and often challenging, especially for patients who are cured of their malignancy but experience continued fatigue.29 Despite biomedical literature documenting this entity, patients with cancer-related fatigue often have difficulty obtaining...
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Ann M. Berger, Kathi Mooney, Amy Alvarez-Perez, William S. Breitbart, Kristen M. Carpenter, David Cella, Charles Cleeland, Efrat Dotan, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Catherine Jankowski, Thomas LeBlanc, Jennifer A. Ligibel, Elizabeth Trice Loggers, Belinda Mandrell, Barbara A. Murphy, Oxana Palesh, William F. Pirl, Steven C. Plaxe, Michelle B. Riba, Hope S. Rugo, Carolina Salvador, Lynne I. Wagner, Nina D. Wagner-Johnston, Finly J. Zachariah, Mary Anne Bergman and Courtney Smith

Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer.

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Crystal S. Denlinger, Robert W. Carlson, Madhuri Are, K. Scott Baker, Elizabeth Davis, Stephen B. Edge, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Elizabeth Kvale, Terry S. Langbaum, Jennifer A. Ligibel, Mary S. McCabe, Kevin T. McVary, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Tracey O’Connor, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian and Deborah Freedman-Cass

Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel’s definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.

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Crystal S. Denlinger, Robert W. Carlson, Madhuri Are, K. Scott Baker, Elizabeth Davis, Stephen B. Edge, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Elizabeth Kvale, Terry S. Langbaum, Jennifer A. Ligibel, Mary S. McCabe, Kevin T. McVary, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Tracey O’Connor, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian and Deborah Freedman-Cass

Cancer treatment, especially hormonal therapy and therapy directed toward the pelvis, can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. Thus, sexual dysfunction is common in survivors and can cause increased distress and have a significant negative impact on quality of life. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for female sexual problems, including those related to sexual desire, arousal, orgasm, and pain.

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Crystal S. Denlinger, Robert W. Carlson, Madhuri Are, K. Scott Baker, Elizabeth Davis, Stephen B. Edge, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Elizabeth Kvale, Terry S. Langbaum, Jennifer A. Ligibel, Mary S. McCabe, Kevin T. McVary, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Tracey O’Connor, Electra D. Paskett, Muhammad Raza, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole McMillian and Deborah Freedman-Cass

Various anticancer treatments, especially those directed toward the pelvis, can damage blood vessels and reduce circulation of blood to the penis and/or damage the autonomic nervous system, resulting in higher rates of erectile dysfunction in survivors than in the general population. In addition, hormonal therapy can contribute to sexual problems, as can depression and anxiety, which are common in cancer survivors. This section of the NCCN Guidelines for Survivorship provides screening, evaluation, and treatment recommendations for male sexual problems, namely erectile dysfunction.

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Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Don Dizon, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Jeffrey Peppercorn, Muhammad Raza, M. Alma Rodriguez, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian and Deborah A. Freedman-Cass

Healthy lifestyle habits have been associated with improved health outcomes and quality of life and, for some cancers, a reduced risk of recurrence and death. The NCCN Guidelines for Survivorship therefore recommend that cancer survivors be encouraged to achieve and maintain a healthy lifestyle, including attention to weight management, physical activity, and dietary habits. This section of the NCCN Guidelines focuses on recommendations regarding nutrition, weight management, and supplement use in survivors. Weight management recommendations are based on the survivor’s body mass index and include discussions of nutritional, weight management, and physical activity principles, with referral to community resources, dietitians, and/or weight management programs as needed.

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Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Don Dizon, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Jeffrey Peppercorn, Muhammad Raza, M. Alma Rodriguez, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment. This portion of the guidelines describes recommendations regarding screening for the effects of cancer and its treatment. The panel created a sample screening tool, specifically for use in combination with the NCCN Guidelines for Survivorship, to guide providers to topics that require more in-depth assessment. Effective screening and assessment can help providers deliver necessary and comprehensive survivorship care.