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Improving the Use of Intravenous Bisphosphonates in Women With Breast Cancer Metastatic to Bone

Joanne Mortimer and Mary Mendelsohn

The City of Hope Comprehensive Cancer Center has a long commitment to the creation of and adherence to treatment guidelines. The NCCN Opportunities for Improvement project provided the institution with a report card for adherence to the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer and the opportunity to determine reasons for nonconcurrence and improve concurrence rates. The institution focused on improving compliance with the use of intravenous bisphosphonates in women with metastatic bone disease.

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Socioeconomic and Clinical Factors Are Key To Uncovering Disparity in Accrual Onto Therapeutic Trials for Breast Cancer

Carolyn E. Behrendt, Arti Hurria, Lusine Tumyan, Joyce C. Niland, and Joanne E. Mortimer

To monitor and address disparity in accrual, patient participation in cancer clinical trials is routinely summarized by race/ethnicity. To investigate whether confounding obscures racial/ethnic disparity in participation, all women with breast cancer treated by medical oncologists at City of Hope Comprehensive Cancer Center from 2004 through 2009 were classified by birthplace and self-reported race/ethnicity, and followed for accrual onto therapeutic trials through 2010. Undetectable on univariate analysis, significantly reduced participation by subjects of African, Asian, Eastern European, Latin American, and Middle Eastern ancestries was revealed after accounting for age, socioeconomic factors, tumor and oncologist characteristics, and intrapractice clustering of patients.

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Serial Assessment of Urinary Incontinence in Breast Cancer Survivors Undergoing (Neo)Adjuvant Therapy

Christopher P. Chung, Carolyn Behrendt, Louise Wong, Sarah Flores, and Joanne E. Mortimer

Background: Among breast cancer survivors, urinary incontinence (UI) is often attributed to cancer therapy. We prospectively assessed urinary symptoms before and after (neo)adjuvant treatment of early-stage breast cancer. Methods: With consent, women with stage I–III breast cancer completed the Urogenital Distress Inventory and the Incontinence Impact Questionnaire before and 3 months after initiating (neo)adjuvant therapy. Patients with UI were at least slightly bothered by urinary symptoms. If UI was present pretreatment, it was considered prevalent; if UI was new or worse at 3 months posttreatment, it was considered incident; if prevalent UI was no worse at 3 months posttreatment, it was considered stable. Ordinal logistic regression models identified characteristics associated with the level of prevalent UI and with the degree of UI impact on quality of life (QoL). Results: On pretreatment surveys, participants (N=203; age 54.5 ± 11.4 years) reported 79.8% prevalence of UI, including overactive bladder (29.1%), stress incontinence (10.8%), or both (39.9%). The level of prevalent UI increased with body mass index (BMI; P<.05). Of 163 participants assessed at both time points, incident UI developed in 12 of 32 patients without prevalent UI and 27 of 131 patients with prevalent UI. Regardless of whether UI was prevalent (n=162), incident (n=39), or stable (n=94) at QoL assessment, the impact of UI increased (P<.01) with the number and severity of UI symptoms, subjective urinary retention, and BMI. Adjusted for those characteristics, incident UI had less impact on QoL (P<.05) than did prevalent or stable UI. Conclusions: We found that UI is highly prevalent at breast cancer diagnosis and that new or worsened UI is common after (neo)adjuvant therapy. Because UI often impairs QoL, appropriate treatment strategies are needed.

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Barriers to Treatment in Patients With Locally Advanced Breast Cancer

Laura Bourdeanu, Thehang Luu, Norma Baker, Suzanne Swain-Cabriales, Cathie T. Chung, Joanne Mortimer, Arti Hurria, Sandra Helton, David Smith, Betty Ferrell, Gloria Juarez, and George Somlo

Delays between presentation and treatment could have a significant effect on breast cancer mortality. The authors hypothesized that patient, physician, and system barriers are all responsible for treatment delays. Therefore, a study was conducted to define prevalent barriers to treatment from the patient’s perspective. A modified 43-item Likert-scale questionnaire was administered to patients with clinical stage III locally advanced breast cancer (LABC) who had experienced a delay in treatment of 3 months or more. Between October 2008 and January 2010, 153 patients presented with LABC; 43 patients (28.1%) met eligibility, and 40 completed the questionnaire. Among the patient barriers reported, 38% of patients delayed care for fear of losing their breast and 47% awaited previously scheduled routine appointments instead of seeking care. Among the physician barriers reported, 20% of physicians of initial contact did not believe the breast lump/symptom was related to cancer and 15% did not believe it needed a biopsy. Among the system barriers reported, the most prevalent were delays in performing diagnostic tests and obtaining insurance authorization for tests, treatment, or physician visits. Substantial delays were seen in 28.1% of patients from presentation to when they sought therapy at City of Hope Comprehensive Cancer Center. The high prevalence of patient barriers versus physician/system barriers suggests that increased educational efforts for patients and health care professionals are needed.

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Studying Cancer-Related Fatigue: Report of the NCCN Scientific Research Committee

Joanne E. Mortimer, Andrea M. Barsevick, Charles L. Bennett, Ann M. Berger, Charles Cleeland, Shannon R. DeVader, Carmen Escalante, Jeffrey Gilreath, Arti Hurria, Tito R. Mendoza, and Hope S. Rugo

NCCN convened a committee of experts to make recommendations for future studies of cancer-related fatigue (CRF). The committee reviewed the current data on the incidence, clinical measurement, and treatment of CRF. The assessment of fatigue is largely derived from self-report questionnaires that address the symptom of fatigue, and do not correlate the presence of fatigue with change in physical activity. The committee developed a self-report questionnaire, NCCN Fatigue and Contributing Factors Inventory, which incorporates assessments of fatigue, pain, difficulty sleeping, distress, physical activity, and concurrent medications. A clinical research study using this measure in conjunction with the NCCN Breast Cancer Outcomes Database Project is planned. The committee noted a strong interaction among fatigue, pain, difficulty sleeping, and distress and recommended that future clinical research address these interactions.

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Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women’s Health Initiative Study

Rebecca A. Nelson, Enrique Soto-Perez-de-Celis, Rowan T. Chlebowski, Mara Schonberg, Joanne Mortimer, Kathy Pan, Lifang Hou, Marian L. Neuhouser, Kerryn W. Reding, Nazmus Saquib, Jean Wactawski-Wende, Emily Wolfson, Mina S. Sedrak, and Laura Kruper

Background: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality. We investigated the use of this index in women aged ≥65 years with breast cancer in the Women’s Health Initiative (WHI). Methods: We calculated 10-year mortality risk scores for 2,549 WHI participants with breast cancer (“cases”) and 2,549 age-matched breast cancer–free participants (“controls”) using Schonberg index risk scoring. Risk scores were grouped into quintiles for comparisons. Risk-stratified observed mortality rates and 95% confidence intervals were compared across cases and controls. Observed 10-year mortality rates in cases and controls were also compared with Schonberg index–based predicted 10-year mortality rates. Results: Compared with controls, cases were more often white (P=.005), had higher income and education levels (P<.001 for both), more often lived with their husband/partner (P<.001), scored higher on subjective health/happiness (P<.001), and needed less assistance in activities of daily living (P<.001). Participants with breast cancer had similar risk-stratified 10-year mortality rates compared with controls (34% vs 33%, respectively). Stratified results showed that cases had slightly higher mortality rates than controls in the lowest risk quintile and lower mortality rates in the 2 highest risk quintiles. Observed mortality rates in cases and controls were similar to Schonberg index–predicted mortality, with model c-indexes of 0.71 and 0.76, respectively. Conclusions: Among women aged ≥65 years with incident breast cancer, the Schonberg index–based risk-stratified 10-year mortality rates were similar to those in women without breast cancer, demonstrating a similar performance of the index among both populations. Along with other health measures, prognostic indexes can help predict survival among older women with breast cancer and support geriatric oncology guidelines that promote using life expectancy calculation tools for shared decision-making.

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NCCN Task Force Report: mTOR Inhibition in Solid Tumors

Robert A. Figlin, Elizabeth Brown, Andrew J. Armstrong, Wallace Akerley, Al B. Benson III, Harold J. Burstein, David S. Ettinger, Phillip G. Febbo, Matthew G. Fury, Gary R. Hudes, Merrill S. Kies, Eunice L. Kwak, Robert J. Morgan Jr., Joanne Mortimer, Karen Reckamp, Alan P. Venook, Frank Worden, and Yun Yen

The mammalian target of rapamycin (mTOR) protein complex functions as an integration center for various intracellular signaling pathways involving cell cycle progression, proliferation, and angiogenesis. These pathways are frequently dysregulated in cancer, and therefore mTOR inhibition is a potentially important antitumor target. Commercially available mTOR inhibitors include rapamycin (i.e., sirolimus) and temsirolimus. Other agents under investigation include everolimus and deforolimus. mTOR inhibition has been studied in various solid tumors, including breast, gynecologic, gastrointestinal, prostate, lung, and head and neck cancers. Studies have focused on mTOR inhibition as a monotherapy or in combination with other drugs based on the principle that inhibiting as many targets as possible reduces the emergence of drug resistance. Temsirolimus is currently the only mTOR inhibitor that is specifically labeled for treatment of solid tumors. However, preclinical studies and early-phase trials are rapidly evolving. Additionally, research is further defining the complicated mTOR pathways and how they may be disordered in specific malignancies. To address these issues, NCCN convened a task force to review the underlying physiology of mTOR and related cellular pathways, and to review the current status of research of mTOR inhibition in solid tumors. (JNCCN 2008;6[Suppl 5]:S1—S20)

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Breast Cancer Risk Reduction, Version 2.2015

Therese B. Bevers, John H. Ward, Banu K. Arun, Graham A. Colditz, Kenneth H. Cowan, Mary B. Daly, Judy E. Garber, Mary L. Gemignani, William J. Gradishar, Judith A. Jordan, Larissa A. Korde, Nicole Kounalakis, Helen Krontiras, Shicha Kumar, Allison Kurian, Christine Laronga, Rachel M. Layman, Loretta S. Loftus, Martin C. Mahoney, Sofia D. Merajver, Ingrid M. Meszoely, Joanne Mortimer, Lisa Newman, Elizabeth Pritchard, Sandhya Pruthi, Victoria Seewaldt, Michelle C. Specht, Kala Visvanathan, Anne Wallace, Mary Ann Bergman, and Rashmi Kumar

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.

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NCCN Guidelines® Insights: Breast Cancer, Version 4.2023

Featured Updates to the NCCN Guidelines

William J. Gradishar, Meena S. Moran, Jame Abraham, Vandana Abramson, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Bethany Anderson, Harold J. Burstein, Helen Chew, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Sara A. Hurvitz, Rachel C. Jankowitz, Sara H. Javid, Jairam Krishnamurthy, A. Marilyn Leitch, Janice Lyons, Joanne Mortimer, Sameer A. Patel, Lori J. Pierce, Laura H. Rosenberger, Hope S. Rugo, Bryan Schneider, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, Mei Wei, Kari B. Wisinski, Jessica S. Young, Kay Yeung, Mary A. Dwyer, and Rashmi Kumar

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.

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Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

William J. Gradishar, Benjamin O. Anderson, Jame Abraham, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Sarah L. Blair, Harold J. Burstein, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Steven J. Isakoff, Jairam Krishnamurthy, Janice Lyons, P. Kelly Marcom, Jennifer Matro, Ingrid A. Mayer, Meena S. Moran, Joanne Mortimer, Ruth M. O'Regan, Sameer A. Patel, Lori J. Pierce, Hope S. Rugo, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, John H. Ward, Jessica S. Young, Jennifer L. Burns, and Rashmi Kumar

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.