Search

e21603 Background: Insomnia is prevalent among cancer survivors. However, screening and treatment is inconsistent across U.S. cancer centers. We sought to identify factors associated with moderate to severe insomnia (MSI) to inform the development of a screening and treatment program for survivors. Methods: As part of a comprehensive supportive care needs assessment, we evaluated the prevalence and correlates of insomnia among patients receiving follow-up cancer care. Patients reported on a 5 point Likert scale (0 = never to 5 = always) how often they have “problems falling or staying asleep”. MSI was defined as those who endorsed “4 = very often” or “5 = always,” and remaining responses were characterized as “No Insomnia” (NI). Descriptive statistics summarized patterns of insomnia and sleep hygiene. Chi-square and Fisher’s exact tests compared differences in sleep hygiene, fatigue, anxiety, depression, and other clinical and demographic characteristics between patients with and without insomnia. Results: Among 312 respondents, 83 (27%) endorsed MSI. Women were more likely to endorse MSI compared to men (32% vs. 19%, p = 0.02). Age was not associated with MSI. MSI was most common among patients with hematologic malignancy (36%), breast cancer (32%), gynecologic cancer (31%), and melanoma (29%). Regarding sleep hygiene: Most reported frequent exposure to bright light before sleep (89% MSI vs. 85% NI). Patients with MSI, compared to NI, were more likely to report watching the clock (86% vs. 75%, p = 0.04) and an irregular sleep schedule (47% vs. 32%, p = 0.02). Patients with MSI were also less likely to meet exercise guidelines (31% vs. 45% NI, p = 0.03) and more likely to report fatigue (29% vs. 14%, p = 0.004). Further, those with MSI were more likely to report anxiety (40% vs. 8%), fear of recurrence (74% vs. 46%), and financial concerns (35% vs. 15%) (all p < 0.001). 67% of patients with MSI were interested in supportive care to address insomnia. Conclusions: A simple one-item screener identified survivors susceptible to moderate to severe insomnia. Interventions beyond attention to sleep hygiene are needed to improve insomnia and its impact on fatigue and emotional distress. The relationships between insomnia, fitness, anxiety and distress merit further evaluation.

9 Background: Optimal follow up care for the 3.1 million breast cancer (BC) survivors in the United States has not been definitively determined. ASCO and NCCN recommend that early stage BC patients have a history and physical by their oncology or primary care provider every 3 to 6 months in the first three years post treatment. Additional visits have not been shown to improve outcomes. However, many patients are seen more frequently, leading to increased healthcare costs. In this context, we developed and implemented a BC care redesign algorithm (BCCRA) to reduce redundant follow up. Methods: The BCCRA multidisciplinary team recommended BC survivors be seen by an oncology provider every 6 months for the first five years post treatment and annually thereafter. Retrospective chart review was conducted to evaluate BCCRA adherence from November 2014 to November of 2015. Patients were deemed ineligible if there was a medically necessary reason for visits outside of the BCCRA such as reconstruction, ongoing treatment or clinical trial participation. Eligible charts were analyzed for adherence. For survivors who did not adhere, charts were analyzed for outcome of additional visits. Results: 116 patient charts reviewed and 72 (62.1%) were deemed ineligible. Of the remaining 44 survivors, 26 (59.1 %) adhered and 18 (40.91%) did not adhere. Of the 18 survivors who did not adhere, six had visits due to clinical concern and 12 had visits due to patient or provider preference. Of the 6 patients who had visits for clinical concern, 4 resulted in a change in the patient’s medical management (CMM). Of the 12 patients who had visits due to patient/provider preference, 2 resulted in a CMM. Conclusions: Despite buy-in from a motivated multidisciplinary team, there were challenges to implementing the BCCRA. 62.1% of patients were ineligible and there was a significant proportion of patients/providers who chose more frequent visit schedules. However, the BCCRA had 59.1% adherence which could result in cost reduction and increased flexibility in oncologists’ schedules. Further evaluation of the model is needed to validate these claims.

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.

Patients in the USA face potentially high financial burdens from the costs of cancer care, distinct from the challenges of societal costs and the economic impact of the disease itself. Survey data suggest that many physicians, let alone many patients, are uninformed about the costs of cancer care. Greater cost transparency and both physician and patient education will be necessary to improve patient understanding of costs and to reduce financial burdens. While many patients wish to discuss costs of care, few report such conversations, and there is no consensus on the optimal setting, timing, content or goals for such discussions. This paper reviews the challenge of appropriately educating patients regarding financial burdens of cancer.

Cancer survivors are at an elevated risk for infection because of immune suppression associated with prior cancer treatments, and they are at increased risk of complications from vaccine-preventable diseases. This section of the NCCN Guidelines for Survivorship provides recommendations for the prevention of infections in survivors through education, antimicrobial prophylaxis, and the judicious use of vaccines. These guidelines provide information about travel and gardening precautions and safe pet care/avoidance of zoonosis, and include detailed recommendations regarding vaccinations that should be considered and encouraged in cancer and transplant survivors.

Comparative effectiveness research aims to inform health-care decisions by patients, clinicians, and policy makers. However, questions related to what information is relevant, and how to view the relative attributes of alternative interventions have political, social, and medical considerations. In particular, questions about whether cost is a relevant factor, and whether cost-effectiveness is a desirable or necessary component of such research, have become increasingly controversial as the area has gained prominence. Debate has emerged about whether comparative effectiveness research promotes rationing of cancer care. At the heart of this debate are questions related to the role and limits of patient autonomy, physician discretion in health-care decision making, and the nature of scientific knowledge as an objective good. In this article, we examine the role of comparative effectiveness research in the USA, UK, Canada, and other health-care systems, and the relation between research and policy. As we show, all health systems struggle to balance access to cancer care and control of costs; comparative effectiveness data can clarify choices, but does not itself determine policy or promote rationing of care.

Overview: The Affordable Care Act (ACA) contains many provisions that affect cancer care. The provisions of health care reform aim to improve access to quality cancer care, particularly among the most vulnerable Americans. However, health care reform also offers many challenges and opportunities that affect every stakeholder in oncology. This article summarizes the ACA provisions relevant to oncology, discusses the ethical implications for the oncology caregiver, and describes the effects on specific oncology stakeholders.

Adjuvant endocrine therapy improves overall survival for women with breast cancer. However, side effects may compromise patients' quality of life (QOL). This study examined how two communication variables (self-efficacy for symptom communication [SE] and holding back from discussing cancer-related concerns [HB]) relate to QOL, pain and menopausal symptoms. Participants with breast cancer (N = 61) completed questionnaires regarding symptoms, communication, and QOL. SE was positively related to QOL and negatively related to pain interference. HB from discussing cancer-related concerns was related negatively to QOL and positively to pain interference. HB mediated the relationship between SE and QOL as well as between SE and pain interference. Increased SE is beneficial among women on endocrine therapy for breast cancer. Future research should determine if interventions to improve SE are feasible and can improve QOL and symptom tolerability.

It has long been observed that young women with breast cancer are more likely to suffer from recurrence and death than older women after diagnosis. In this issue, Anders et al explore the potential biologic basis for differences in outcomes and argue that breast cancer in younger women is a unique biologic entity. Their study confirms prior work demonstrating that breast cancers in young women are characterized by lower levels of estrogen receptor (ER) expression and higher grade. In addition, through analysis of both immunohistochemistry (IHC) and mean mRNA levels, they found that breast cancers in younger women, defined in this study as age 45 years, have higher levels of human epidermal growth factor receptor 2 (HER-2) expression compared with women age 65 years, a correlation not found consistently in prior population-based studies. Although this work confirms that the distribution of breast cancer characteristics varies based on age at presentation, to this point, there would be little basis to claim that breast cancer in younger women is a separate disease. However, in addition to exploring differences among these wellcharacterized features of breast cancer, these investigators also explored differences in gene expression for thousands of genes that might distinguish one tumor from another in this combined data set. Using single-gene analysis and focusing on the 50 genes with greatest differences among tumor samples, they were unable to identify additional features that consistently distinguished tumors from younger versus older women. However, Anders et al also used gene set enrichment analysis, which is a technique specifically designed to evaluate groups of genes with common function or from common pathways to identify similarities that may not emerge with single-gene analysis. Using this forest versus trees approach, Anders et al found overexpression of multiple gene sets involved in immune function, cell signaling, survival, and several other pathways of interest that could reliably differentiate tumors in younger women at the molecular level from tumors of older women. On the basis of these admittedly exploratory findings, the authors contend that breast cancer in young women has unique biologic features and, by extension, deserves consideration as a distinct form of breast cancer. This research joins a rapidly expanding body of literature revealing the heterogeneity of breast cancer at the molecular level. Although there are many possible explanations for differences in outcomes among patients, it is clear that underlying differences in tumor biology play a large role. The question then becomes how we can best use this information to characterize the disease in individual patients to inform prognosis and choice of therapy, as well as to focus future research. This also raises more general questions confronting breast cancer clinicians and researchers regarding how many discrete forms of breast cancer exist and consideration of the value and potential costs in distinguishing them. It is important to note that initial progress in development of medical therapy arose from the recognition of discrete diseases that were fundamentally similar from patient to patient, allowing meaningful comparisons of outcomes and, later, development of clinical trials. The conceptual shift in viewing disease as a specific entity comparable across patients, rather than a personal state of underlying imbalance in humors or other elements varying from patient to patient, coupled with the rise of hospitals where similar patients were clustered and development of biostatistics, which provided the tools for comparison, was fundamental to what historian Charles Rosenberg has termed the Therapeutic Revolution. The pioneering work of Pierre Louis in 1836 in recognizing that blood letting was no more effective than diet and rest for treatment of pneumonia could not occur until pneumonia was recognized as sufficiently similar from one patient to the next to justify comparing outcomes. It should also be noted that much of the initial benefit from this conceptual advance was not in developing new therapies but, instead, in abandoning those that did not work. It was during this period of first evaluating established interventions in newly defined diseases that Oliver Wendell Holmes famously remarked to his students at Harvard that “if the whole materia medica [standard medical therapies] could be sunk to the bottom of the sea, it would be all the better for mankind and all the worse for the fishes.” Although recognition of discrete subtypes of breast cancer need not induce a similar state of therapeutic nihilism, it is important to consider how and when we know we are dealing with a distinct disease and what the consequences of this for both current practice and research may be. Until relatively recently, breast cancer was viewed as one disease, albeit with variable features that could affect prognosis and treatment options. Differences between ER-positive disease and ER-negative disease in terms of both natural history and response to therapy have been well documented, but studies demonstrating the potential for changes in receptor expression over time contributed to the notion that there was one underlying condition. Even when the importance of HER-2 overexpression leading to inferior outcomes in a subset of breast cancers was first recognized in 1987, this was essentially considered a poor-prognosis feature of the disease, rather than a discrete entity. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 20 JULY 1

Costs of cancer care in the United States are projected to rise from $124.6 billion in 2010 to approximately $174 billion in 2020, contributing to an emerging consensus that health care spending is on an unsustainable trajectory. With the annual cost of novel therapies often exceeding twice the US median household income of $50,000, access to quality care for individual patients is threatened. Costs of care can lead to financial distress and even bankruptcy. For the health system as a whole, health care spending consumes a growing proportion of federal and state budgets. Rising costs threaten the viability of public health insurance programs, including Medicare and Medicaid, as well as spending on other social priorities, including cancer research. Controlling costs while improving access to quality care and continuing to support innovation thus poses a critical challenge. In considering this problem, it is important to recognize that concerns over cost and access to health care are not new. These concerns were behind efforts at reform under Presidents Nixon in the 1970s and Clinton in the 1990s. Previous reform efforts have been subject to labels of socialized medicine and branded anti-American. Recent efforts to expand access and control costs under the Affordable Care Act have met the same discord and demagoguery. The US public has long endorsed the concept of health care reform, but it has been divided over the nature of reform and how it should be achieved. Writing in 1984 about the “schizophrenia” of the nation over health care costs, and summarizing multiple public opinion polls from that time, Blendon and Altman explained that although controlling costs was viewed as the number one health care priority for the nation, it was not viewed as a top national priority, compared with unemployment, government spending, defense, and other areas. Furthermore, they found that although Americans were deeply concerned with the rising costs of health care for themselves as individual patients, they were not particularly troubled by rising societal spending on health care, and some favored greater national spending on health. We hope to control costs along with improving access and quality; however, it is not clear that cost control can be achieved without facing hard choices. The proportion of the US gross domestic product spent on health care costs has been steadily rising since the enactment of Medicare in 1965. This rise has been driven by multiple factors, including the growth and development of new technologies, an aging population, increased use of tests and scans, and reimbursement policies for physicians, hospitals, and other providers that incentivize delivery of more services. Although many countries struggle with high costs of health care, the United States is somewhat unique in that we prohibit consideration of cost effectiveness in our public health insurance system. At its inception, Medicare was established with a statutory obligation to cover any care deemed reasonable and necessary, but precisely how this should be defined is the subject of ongoing political debate. In this context, Gogineni et al sought to understand current concerns over health care costs among physicians, patients with cancer, and members of the general public, with a focus on Medicare and potential methods to control Medicare spending. They achieved response rates consistent with expectations in similar populations (at roughly three quarters of eligible patients and 50% of selected oncologists and members of public). Some response bias must be considered when interpreting results, with 50% of patients and oncologists self-identifying as Democrats versus roughly one third identifying as Republicans. Approximately three quarters of respondents agreed that Medicare spending was a substantial national problem, and roughly two thirds thought Medicare spending could be reduced without harming health outcomes. The vast majority of each group felt that both pharmaceutical industry and private health insurance company behaviors contributed to high costs. Roughly 80% of the public and approximately 70% of patients and oncologists also believed that unnecessary treatments contributed to high costs. Not surprisingly, larger differences emerged over the question of excessive physician charges, with approximately 80% of the public, 67% of patients with cancer, and only 19% of oncologists viewing this as an important factor. These data highlight the extent to which multiple stakeholders are concerned about costs of care and suggest that there is consensus on potential to reduce unnecessary health care spending without restricting high-value care. Indeed, this is the premise behind the American Board of Internal Medicine Choosing Wisely campaign, through which the American Society of Clinical Oncology and other specialty organizations have identified practices that should be eliminated to lower costs with no adverse impact on quality (and, in some cases, improvement). The challenge of drawing firm policy conclusions from survey work becomes apparent when considering the question of Medicare adopting reference pricing for cancer drugs. Gogineni et al found that 75% of respondents agreed that Medicare should not pay for more expensive treatments when equally effective alternatives were available. They then argue that this indicates widespread support for reference pricing, in which reimbursement for an intervention is set at the rate of the lowest cost equivalent. One might question why 100% JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 8 MARCH 1

Background Research studies involving human tissue are increasingly common. However, patients' attitudes toward research biopsies are not well characterized, particularly when the biopsies are carried out outside the context of therapeutic trials. Patients and methods One hundred sixty patients with metastatic breast cancer (MBC) from two academic (n = 80) and two community (n = 80) hospitals completed a 29-item self-administered survey to evaluate their willingness to consider providing research purposes only biopsies (RPOBs) (as a stand-alone procedure) and additional biopsies (ABs) (additional needle passes at the time of a clinically indicated biopsy). Results Eighty-two (51%) of 160 patients would consider having RPOBs, of which 42 (53%) and 40 (50%) patients were from academic and community hospitals, respectively. Patients who had more prior biopsies were less likely to consider RPOBs (RR = 0.6, 95% CI: 0.4–1.0, P = 0.03). Of 160 patients, 115 (72%) patients would consider having ABs. Of these, 64 (80%) and 51 (64%) patients from academic and community hospitals, respectively, would consider ABs (RR = 1.2, 95% CI: 1.0–1.5, P = 0.03). Conclusions Many patients with MBC in both academic and community settings report willingness to consider undergoing biopsies for research. Further research is needed to understand ethical, logistical and provider-based barriers to broader participation in such studies.

Learning Objectives Describe the experiences of insured cancer patients requesting copayment assistance in order to better understand the challenges of underinsurance. Describe the impact of costs on the well being of insured cancer patients. Evaluate the impact of costs on the treatment received by insured cancer patients. Purpose. Cancer patients carry rising burdens of health care-related out-of-pocket expenses, and a growing number of patients are considered “underinsured.” Our objective was to describe experiences of insured cancer patients requesting copayment assistance and to describe the impact of health care expenses on well-being and treatment. Methods. We conducted baseline and follow-up surveys regarding the impact of health care costs on well-being and treatment among cancer patients who contacted a national copayment assistance foundation along with a comparison sample of patients treated at an academic medical center. Results. Among 254 participants, 75% applied for drug copayment assistance. Forty-two percent of participants reported a significant or catastrophic subjective financial burden; 68% cut back on leisure activities, 46% reduced spending on food and clothing, and 46% used savings to defray out-of-pocket expenses. To save money, 20% took less than the prescribed amount of medication, 19% partially filled prescriptions, and 24% avoided filling prescriptions altogether. Copayment assistance applicants were more likely than nonapplicants to employ at least one of these strategies to defray costs (98% vs. 78%). In an adjusted analysis, younger age, larger household size, applying for copayment assistance, and communicating with physicians about costs were associated with greater subjective financial burden. Conclusion. Insured patients undergoing cancer treatment and seeking copayment assistance experience considerable subjective financial burden, and they may alter their care to defray out-of-pocket expenses. Health insurance does not eliminate financial distress or health disparities among cancer patients. Future research should investigate coverage thresholds that minimize adverse financial outcomes and identify cancer patients at greatest risk for financial toxicity.

We examined cardiorespiratory fitness (CRF) levels in early stage breast cancer patients and determined whether CRF differs as a function of adjuvant therapy regimen. A total of 180 early breast cancer patients representing three treatment groups (surgery only, single-, and multi-modality adjuvant therapy) in the Cooper Center Longitudinal Study (CCLS) were studied. A non-cancer control group (n = 180) matched by sex, age, and date of the CCLS visit was included. All subjects underwent an incremental exercise tolerance test to symptom limitation to assess CRF (i.e., peak metabolic equivalents [METs] and time to exhaustion). The mean time from breast cancer diagnosis to exercise tolerance testing was 7.4 ± 6.2 years. In adjusted analyses, time to exhaustion and peak METs were incrementally impaired with the addition of surgery, single-, and multi-modality adjuvant therapy compared to those of matched controls (p = 0.006 and 0.028, respectively). CRF was lowest in the multi-modality group compared to all other groups (all p's < 0.05). Despite being 7 years post-diagnosis, asymptomatic early breast cancer survivors have marked reductions in CRF. Patients treated with multi-modal adjuvant therapy have the greatest impairment in CRF.

Purpose The landscape of managing potential conflicts of interest (COIs) has evolved substantially across many disciplines in recent years, but rarely are the issues more intertwined with financial and ethical implications than in the health care setting. Cancer care is a highly technologic arena, with numerous physician-industry interactions. The American Society of Clinical Oncology (ASCO) recognizes the role of a professional organization to facilitate management of these interactions and the need for periodic review of its COI policy (Policy). Methods To gauge the sentiments of ASCO members and nonphysician stakeholders, two surveys were performed. The first asked ASCO members to estimate opinions of the Policy as it relates to presentation of industry-sponsored research. Respondents were classified as consumers or producers of research material based on demographic responses. A similar survey solicited opinions of nonphysician stakeholders, including patients with cancer, survivors, family members, and advocates. Results The ASCO survey was responded to by 1,967 members (1% of those solicited); 80% were producers, and 20% were consumers. Most respondents (93% of producers; 66% of consumers) reported familiarity with the Policy. Only a small proportion regularly evaluated COIs for presented research. Members favored increased transparency about relationships over restrictions on presentations of research. Stakeholders (n = 264) indicated that disclosure was “very important” to “extremely important” and preferred written disclosure (77%) over other methods. Conclusion COI policies are an important and relevant topic among physicians and patient advocates. Methods to simplify the disclosure process, improve transparency, and facilitate responsiveness are critical for COI management.

6542Background: Mammography screening reduces breast cancer mortality, but there is ongoing controversy over optimal target population and interval. We sought to explore the association between scr...

e18269Background: Limited transparency exists regarding eligibility and benefits for PAPs. Little is known about the extent of financial assistance provided by PAPs to reduce costs for prescription...

In an era of guideline propagation, this case helps raise the question, Does quality cancer care now require that we always follow guidelines exactly, or do some circumstances still require a more individualized approach?

Purpose An American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This PCO addresses the integration of palliative care services into standard oncology practice at the time a person is diagnosed with metastatic or advanced cancer. Clinical Context Palliative care is frequently misconstrued as synonymous with end-of-life care. Palliative care is focused on the relief of suffering, in all of its dimensions, throughout the course of a patient's illness. Although the use of hospice and other palliative care services at the end of life has increased, many patients are enrolled in hospice less than 3 weeks before their death, which limits the benefit they may gain from these services. By potentially improving quality of life (QOL), cost of care, and even survival in patients with metastatic cancer, palliative care has increasing relevance for the care of patients with cancer. Until recently, data from randomized controlled trials (RCTs) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving standard oncology care have not been available. Recent Data Seven published RCTs form the basis of this PCO. Provisional Clinical Opinion Based on strong evidence from a phase III RCT, patients with metastatic non–small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care—when combined with standard cancer care or as the main focus of care—leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. NOTE. ASCO's provisional clinical opinions (PCOs) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and settings for further research. Because of the rapid flow of scientific information in oncology, new evidence may have emerged since the time a PCO was submitted for publication. PCOs are not continually updated and may not reflect the most recent evidence. PCOs cannot account for individual variation among patients and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It is the responsibility of the treating physician or other health care provider, relying on independent experience and knowledge of the patient, to determine the best course of treatment for the patient. Accordingly, adherence to any PCO is voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. ASCO PCOs describe the use of procedures and therapies in clinical trials and cannot be assumed to apply to the use of these interventions in the context of clinical practice. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO's PCOs, or for any errors or omissions.

BACKGROUND: The rapid pace of genetics research, coupled with evolving standards for informed consent, can create ethical challenges regarding future use of tissue or information from completed clinical trials. The Cancer and Leukemia Group B (CALGB) Oncology Cooperative Group was faced with an ethical dilemma regarding sharing genetic data from a completed genome-wide association study (GWAS) that was conducted as part of a large, multicenter breast cancer clinical trial with a national database: the Database of Genotypes and Phenotypes National Center for Biotechnology Information (dbGaP). METHODS: The CALGB Ethics Committee conducted a series of multidisciplinary meetings and teleconferences involving patient advocates, bioethicists, clinical researchers, and clinical oncologists to evaluate the ethical issues raised by this case and to identify lessons for improving informed consent to future genetics research in oncology trials. RESULTS: The Ethics Committee recommended that GWAS data be provided to dbGaP consistent with documented consent for future use of tissue among trial participants. Ethical issues, including adequacy of informed consent to future research, limitations of privacy in modern genetics research, the potential impact of population-based genetics research on health disparities, and recontact of research participants for clinical care or further research, were identified as major ethical considerations in this area. CONCLUSIONS: Although modern standards for informed consent should not prohibit research or sharing of data consistent with participant's intent and the public interest, there is an urgent need for national consensus on the appropriate use of archived tissue and standardized informed consent for future research among cancer clinical trial participants. Cancer 2012. © 2012 American Cancer Society.

Observed racial/ethnic disparities in the process and outcomes of breast cancer care may be explained, in part, by structural/organizational characteristics of health care systems. We examined the role of surgical facility characteristics and distance to care in explaining racial/ethnic variation in timing of initiation of guideline-recommended radiation therapy (RT) after breast conserving surgery (BCS). We used Surveillance Epidemiology and End Results-Medicare data to identify women ages 65 and older diagnosed with stages I-III breast cancer and treated with BCS in 1994-2002. We used stepwise multivariate logistic regression to examine the interactive effects of race/ethnicity and facility profit status, teaching status, size, and institutional affiliations, and distance to nearest RT on timing of RT initiation, controlling for known covariates. Among 38,574 eligible women who received BCS, 39% received RT within 2 months, 52% received RT within 6 months, and 57% received RT within 12 months post-diagnosis, with significant variation by race/ethnicity. In multivariate models, women attending smaller surgical facilities and those with on-site radiation had higher odds of RT at each time interval, and women attending governmental facilities had lower odds of RT at each time interval (P < 0.05). Increasing distance between patients' residence and nearest RT provider was associated with lower overall odds of RT, particularly among Hispanic women (P < 0.05). In fully adjusted models including race-by-distance interaction terms, racial/ethnic disparities disappeared in RT initiation within 6 and 12 months. Racial/ethnic disparities in timing of RT for breast cancer can be partially explained by structural/organizational health system characteristics. Identifying modifiable system-level factors associated with quality cancer care may help us target policy interventions that can reduce disparities in outcomes.

BACKGROUND:Patient advocates are increasingly involved in cooperative group trials, single-institution cancer programs, and peer-review of research applications. The purpose of this study was to evaluate the role and value of patient advocates from the perspective of Cancer and Leukemia Group B (CALGB) advocates and investigators.METHODS:An online survey was sent to current and past (within 5 years) patient advocates and investigators.RESULTS.Response rates were 72.7% (16 of 22) for advocates and 56.4% (102 of 181) for investigators. Patient advocates were more likely than investigators to report the following: the clinical trial process benefited from advocate involvement on committees (100% of advocates vs 72.1% of investigators;P

The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.

Adherence to consensus guidelines for cancer care may vary widely across health care settings and contribute to differences in cancer outcomes. For some women with breast cancer, omission of adjuvant chemotherapy or delays in its initiation may contribute to differences in cancer recurrence and mortality. We studied adjuvant chemotherapy use among women with stage II or stage III, hormone receptor–negative breast cancer to understand health system and socio-demographic correlates of under-use and delayed adjuvant chemotherapy. We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to examine the patterns of care for 6,678 women aged 65 and older diagnosed with stage II or stage III hormone receptor–negative breast cancer in 1994–2002, with claims data through 2007. Age-stratified logistic regression was employed to examine the potential role of socio-demographic and structural/organizational health services characteristics in explaining differences in adjuvant chemotherapy initiation. Overall utilization of guideline-recommended adjuvant chemotherapy peaked at 43% in this population. Increasing age, higher co-morbidity burden, and low-income status were associated with lower odds of chemotherapy initiation within 4 months, whereas having positive lymph nodes, more advanced disease, and being married were associated with higher odds (P < 0.05). Health system–related structural/organizational characteristics and race/ethnicity offered little explanatory insight. Timely initiation of guideline-recommended adjuvant chemotherapy was low, with significant variation by age, income, and co-morbidity status. Based on these findings, future studies should seek to explore the more nuanced reasons why older women do not receive chemotherapy and why delays in care occur.

Purpose We examined the feasibility of using CYP2D6 genotyping to determine optimal tamoxifen dose and investigated whether the key active tamoxifen metabolite, endoxifen, could be increased by genotype-guided tamoxifen dosing in patients with intermediate CYP2D6 metabolism. Patients and Methods One hundred nineteen patients on tamoxifen 20 mg daily ≥ 4 months and not on any strong CYP2D6 inhibiting medications were assayed for CYP2D6 genotype and plasma tamoxifen metabolite concentrations. Patients found to be CYP2D6 extensive metabolizers (EM) remained on 20 mg and those found to be intermediate (IM) or poor (PM) metabolizers were increased to 40 mg daily. Eighty-nine evaluable patients had tamoxifen metabolite measurements repeated 4 months later. Results As expected, the median baseline endoxifen concentration was higher in EM (34.3 ng/mL) compared with either IM (18.5 ng/mL; P = .0045) or PM (4.2 ng/mL; P < .001). When the dose was increased from 20 mg to 40 mg in IM and PM patients, the endoxifen concentration rose significantly; in IM there was a median intrapatient change from baseline of +7.6 ng/mL (−0.6 to 23.9; P < .001), and in PM there was a change of +6.1 ng/mL (2.6 to 12.5; P = .020). After the dose increase, there was no longer a significant difference in endoxifen concentrations between EM and IM patients (P = .84); however, the PM endoxifen concentration was still significantly lower. Conclusion This study demonstrates the feasibility of genotype-driven tamoxifen dosing and demonstrates that doubling the tamoxifen dose can increase endoxifen concentrations in IM and PM patients.

Inherited or Familial Alzheimer's Disease (FAD) has clearly been shown to be a genetically heterogeneous disorder. Mutations in the gene on chromosome 21 encoding the beta-amyloid protein precursor (APP) have been shown to be linked to 2-3% of FAD kindreds examined around the world. A late onset FAD locus has been mapped to a region of chromosome 19 in which a recently isolated APP-like gene, APLP1 has also been localized, making this gene a strong candidate to harbor a late-onset FAD defect. More recently, a major FAD locus has been mapped to the long arm of chromosome 14. The chromosome 14 locus appears to be mainly linked to the gene defect in early onset FAD pedigrees. Besides the FAD loci on chromosome 21, 19, and 14, at least two other loci must exist since the gene defect in some early- and late-onset FAD pedigrees do not appear to segregate with markers from any of these autosomes. As different gene defects responsible for various forms of FAD are discovered, perhaps, a common basis for the etiology of this devastating disorder can be discerned.

As health care and immigration policies evolve, oncologists may be faced with challenges regarding care for undocumented immigrants, and must stay abreast of changes in federal and state legal statutes as well as medical ethics guidelines.

Over the past decade, research and clinical interest in the therapeutic effectiveness of exercise after cancer diagnosis has greatly increased.1 Positive findings from the first generation of exercise oncology studies, and growing patient demand led the American College of Sports Medicine (ACSM) to assemble an expert panel to formulate exercise guidelines for patients with cancer.2 This comment presents a practical approach to screening and prescribing exercise for patients with cancer. Systematic reviews indicate that exercise is a safe, well-tolerated intervention for patients with curative disease, both during and after adjuvant therapy.3 However, patients with cancer are often older, have a range of comorbid diseases, and receive a diverse range of locoregional and systemic cytotoxic therapies that could increase the risk of exercise-related complications, particularly in sedentary individuals. By incorporating formalised pre-exercise screening into standard practice, oncologists can provide safe and more accurate exercise guidance for patients. A careful history and physical examination of cardiac, pulmonary, neurological, and musculoskeletal signs and symptoms can be used to assess the safety of exercise in patients, or the need for further evaluation. Procedures such as the Physical Activity Readiness Questionnaire or PARmed-X can facilitate the screening process. Patients at moderate or high-risk and those with a positive initial screen should be referred for a symptom-limited exercise stress testing with electrocardiograph diagnostics. ACSM guidelines recommend that patients with cancer should participate in at least 150 min of moderate exercise (eg, brisk walking, light swimming) or 75 min per week of vigorous exercise (eg, jogging, running, hard swimming).2 However, this recommendation is a long-term goal and is not advised as an initial prescription for most sedentary patients either during or immediately after cytotoxic therapy. The key to safe and effective exercise prescriptions is individualisation of the programme to patients’ needs. Providing cancer patients with individually tailored exercise prescriptions is challenging given the considerable variation in pathophysiology, therapeutic management, and prognosis between malignancies and individual patients. Nevertheless, individualised prescriptions can be provided in most scenarios if the fundamental principles of exercise prescription are followed: frequency (sessions per week), intensity (how hard per session), time (session duration), and type (exercise modality)—or the F.I.T.T principle. For individualised exercise prescriptions (figure), the first question should focus on present exercise behaviour. Patients who meet the ACSM guidelines can maintain present behaviour, but 150 min of moderate or 75 min of vigorous exercise per week should be the minimal amount of exercise needed to gain health benefits. Increases in exercise beyond these minimal amounts can lead to further health benefits. Such benefits can be achieved by varying the intensity, frequency, duration, and type of exercise every 2–3 weeks to reduce boredom and ensure continuous improvements in cardiorespiratory fitness. For sedentary patients or those who do not meet the ACSM guidelines, the figure presents a progressive exercise prescription that can be discussed in routine clinical visits. Whether one type of exercise is more effective than another at improving exercise tolerance or symptoms in patients with cancer is not known. Walking is often the preferred choice for most patients, although stationary cycling might be more appropriate for older patients and those who have gait or coordination difficulties. Prescription of the appropriate intensity of exercise is challenging. Intensity of exercise can be explained practically to patients with the talk-test whereby moderate exercise is activity during which one can comfortably hold a conversation, and vigorous exercise is defined as activity that precludes comfortable conversation. More accurate methods are available that use ratings for perceived exertion or heart-rate training zones. Such training zones can be calculated with either age-sex-predicted equations or, preferably, heart-rate responses obtained from the exercise stress test. The addition of resistance training to comprehensive exercise prescription is crucial to increase muscle mass and prevent deterioration in all patients with cancer. The decision of when to include resistance training in the exercise prescription depends on the patient’s needs. In patients with cancer or treatment-related cachexia, or in those whose aerobic exercise is contraindicated, resistance training should be the central focus. In other scenarios, however, it might be more appropriate to start resistance training once aerobic training is part of a patient’s habitual activity. Figure A general approach to individualised exercise prescriptions4 In summary, findings indicate that sedentary behaviour and decreased exercise levels are associated with de-conditioning, poor symptom control, and possibly a poor clinical outcome after cancer diagnosis. Exercise tolerance and several patient-reported outcomes can be improved with structured exercise training across a range of oncological settings. Oncology professionals have a considerable influence on the levels of patient exercise5 and we emphasise the importance of exercise counselling with frequent follow-up whenever appropriate. The ASCM exercise guidelines represent a major benchmark in exercise-oncology research and oncology management. The steps that we describe can help oncology professionals to integrate exercise therapy into their practice. Advancements in the field will continue to modify and refine these guidelines to ensure optimum safety and efficiency of exercise for patients with cancer.

OPThe benefits of exercise in patients with chronic disease have been studied extensively over the last half century. In contrast, investigation of the role of exercise following a diagnosis of cancer has received comparably less attention. In this article, we review the efficacy of exercise training in specific areas across the cancer survivorship continuum [i.e., pre-surgery, post-surgery during adjuvant therapy, following the completion of primary adjuvant therapy (survivorship), and palliation], with a view toward future research. The current evidence base provides strong but preliminary evidence that exercise training is a well-tolerated and safe adjunct therapy that can mitigate several common treatment-related side-effects among cancer patients with early disease both during and following adjuvant therapy although many questions remain unanswered. Preliminary evidence in this area supports that exercise therapy may be an important consideration in multidisciplinary management of patients following a cancer diagnosis.

Clinical investigators in oncology are increasingly interested in using molecular analysis of cancer tissue to understand the biologic bases of response or resistance to novel interventions and to develop prognostic and predictive biomarkers that will guide clinical decision making. Some scientific questions of this nature can only be addressed, or may best be addressed, through the conduct of a clinical trial in which research biopsies are obtained from all participants. However, trial designs with mandatory research biopsies have raised ethical concerns related to the risk of harm to participants, the adequacy of voluntary informed consent, and the potential for misunderstanding among research participants when access to an experimental intervention is linked to the requirement to undergo a research biopsy. In consideration of the ethical and scientific issues at stake in this debate, the Cancer and Leukemia Group B Ethics Committee proposes guidelines for clinical trials involving mandatory research biopsies. Any cancer clinical trial that requires research biopsies of participants must be well designed to address the scientific question, obtain the biopsy in a way that minimizes risk, and ensure that research participants are fully informed of the risks, rationale, and requirements of the study, as well as of treatment alternatives. Further guidelines and discussions of this issue are specified in this position paper. We feel that if these principles are respected, an informed adult with cancer can both understand and voluntarily consent to participation in a clinical trial involving mandatory research biopsy for scientific end points.

The history of clinical trials and the pharmaceutical industry is closely tied to the history of bioethics, which shape the regulation of clinical research and pharmaceutical development. The history of clinical trials begins with the recognition of disease as a discrete condition that is similar enough from patient to patient to allow the rational application of the experimental method to determine which therapies work and which do not. This article presents an overview of some of the key developments and ongoing issues that should serve as an introduction to the rich history of clinical trials and the rise of the pharmaceutical industry. Keywords: clinical trials; pharmaceutical industry; therapeutics; bioethics

Despite recent advances in hormonal therapy for breast cancer, tamoxifen remains a major therapeutic option, with indications ranging from primary prevention to metastatic disease. Understanding the variation in response to tamoxifen may significantly improve our ability to personalize cancer care and maximize therapeutic efficacy. One area of particular interest is the impact of cytochrome P450 CYP2D6 genetic polymorphisms on tamoxifen metabolism. Tamoxifen is considered a prodrug, whose efficacy may be dependent on active metabolites, including endoxifen. Patients with reduced CYP2D6 enzymatic activity tend to have lower endoxifen levels, but clinical relevance of reduced endoxifen levels remains to be determined. Several small to moderately sized retrospective studies have suggested an intriguing association between poor metabolizer status and increased disease recurrence. However, these data are limited by sample size and methodologic challenges, including the inability to adjust for major prognostic and confounding factors. Several subsequent studies have failed to find an association or found improved outcomes among reduced CYP2D6 metabolizers. Therefore, current findings are conflicting and should be considered preliminary. Nevertheless, the CYP2D6 test is commercially available, making clinical use possible even as evidence in this area is still evolving. More definitive clinical research is needed before routine CYP2D6 testing can be recommended and considered standard of care. Anticipated data from retrospective analysis of large adjuvant randomized trials of tamoxifen should help address the clinical utility of CYP2D6 testing.

Breast cancer among young women is rare and often associated with high-risk features. Age alone has been shown to be an independent risk factor for recurrence, although the biologic explanation for the increased risk among younger women remains unknown. Due to the higher risk of recurrence and otherwise typically good health of young women with breast cancer, one must carefully consider both the maximally effective approach to treatment and the potential long-term consequences of therapy. This manuscript focuses on the clinical decisions that we confront when considering systemic therapy for young women with early-stage breast cancer and the evolving data to guide the care of these patients.

Breast cancer remains the most common malignancy diagnosed among women with 182,460 cases estimated in the United States during the year 2008. Although the incidence of breast cancer appears to be ...

Background. As new genomic technology expands the number of medical tests available to physicians and patients, identifying gaps in our understanding of how best to communicate risk is increasingly important. We examined how health literacy informs breast cancer survivors' understanding of and meaning assigned to recurrence risks yielded by genomic tests. Methods. Study participants were posttreatment female breast cancer survivors (N =163 ) recruited at a university breast cancer clinic. We assessed their health literacy (using REALM) and their interpretation of hypothetical recurrence risk results from a genomic test, presented in several verbal and numerical formats. Analyses controlled for women's objective recurrence risk, age, income, and race. Results. Women with lower health literacy gave higher mean estimates of recurrence risk for a hypothetical group of women with early-stage breast cancer than did women with higher health literacy (52% v. 30%, P < 0:001 ). Women with lower health literacy also gave more variable estimates in this and several other tasks. When making chemotherapy decisions using risks presented in verbal formats, decisions by women with lower health literacy were less sensitive to the difference between low and high recurrence risk. Ease of understanding of risk formats differed by health literacy. Conclusions. Health literacy affected the meanings women assigned to recurrence risk when presented in certain formats. The greater variability in responding by women with lower health literacy supports the hypothesis that they have less precise mental representations of risk, but more research is needed to rule out other possible explanations.

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment.

9557 Background: Patients undergoinghematopoietic stem cell transplantation (HCT) experience a steep deterioration in quality of life (QOL) and mood during hospitalization for HCT. The impact of this deterioration on patients’ long-term QOL and post-traumatic stress disorder (PTSD) symptoms is unknown. Methods: We conducted a prospective longitudinal study of patients hospitalized for HCT. At baseline (day-6), day+1, day+8, and 6 months post-HCT, we assessed QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]) and mood (Hospital Anxiety and Depression Scale [HADS]). We used the PTSD Checklist to assess for PTSD symptoms at 6 months. We used multivariable linear regression models to identify predictors of QOL and PTSD symptoms at 6 months post-HCT. Results: We enrolled 97% (90/93) of consecutively eligible patients undergoing autologous (n = 30), myeloablative allogeneic (n = 30), or reduced intensity allogeneic (n = 30) HCT. Overall, patients’ QOL at 6 months (mean FACT-BMT...

e20645 Background: Adjuvant endocrine therapy (ET) plays an important role in reducing risk of recurrence among women with hormone receptor positive breast cancer. Although the literature suggests ...

Introduction: Zoledronic acid (ZA) in combination with endocrine therapy (ET) and ovarian ablation yielded a disease-free survival and overall survival advantage in women with estrogen receptor+ early stage breast cancer (EBC). Evidence from preclinical studies suggests that ZA increases gamma/delta T cells (GDT). Materials and Methods: We examined immune responses following ZA in 24 BC patients by collecting peripheral blood mononuclear cells at day 0, 1, 7, and 28. GDT population and cytokine responses were assayed using flow cytometry and multi-analyte profiling beads (Luminex), respectively, and relative changes from baseline were analyzed using the Wilcoxon signed-rank test. Results: In total, 18 (75%) patients had metastatic breast cancer (MBC), 6 (25%) had EBC, 18 (75%) received ET, 4 (17%) chemotherapy (C), and 2 (8%) no concurrent therapy. Following ZA, an increase in both effector (CD3+/Vdelta2+/CD45RA−/CD27−) ( P = 0.0005) and central memory GDT (CD3+/Vdelta2+/CD45RA−/CD27+) ( P = 0.006), as well as a decrease in naive GDT (CD3+/Vdelta2+/CD45RA+/CD27+) ( P = 0.003) were observed at day 7. Cytokines, including interleukin-1 (IL-1) receptor antagonist ( P P P P P Conclusion: In both EBC and MBC patients, ZA appears to induce a significant change in GDTs and cytokines associated with cell-mediated immunity offering a possible biologic mechanism for ZA's anticancer activity. Further studies are necessary to determine which BC patients might achieve clinically meaningful anticancer benefits from ZA.

161 Background: Growing evidence suggests that financial distress is a side effect of cancer care needing attention. Little is known about how patients cope with treatment-related financial distress. This study describes how patients with cancer cope with treatment-related costs and identifies those at greatest risk for using potentially harmful cost-coping strategies. Methods: Eligible patients for this cross-sectional, survey study were adults being treated for solid malignancies enrolled June 2010 to May 2011 in a national copay assistance program. Coping strategies were grouped as lifestyle-altering or care-altering. Descriptive statistics and analysis of variance assessed coping strategies and relationships between covariates. Results: Among 174 participants, 89% used at least one lifestyle-altering strategy to cope with costs, while 39% used a care-altering strategy. Most common care-altering coping strategies included: not filling a prescription (28%); and taking less medication than prescribed (23%). Lifestyle-altering strategies included: spending less on leisure activities (77%); spending less on basics (57%); borrowing money (54%); and spending savings (50%). The mean number of coping strategies was higher for patients < 65 than for those ≥ 65 (Table). Lower-income patients used more care-altering strategies than higher-income patients. Patients with more education and shorter duration of chemotherapy adopted more lifestyle-altering strategies than their counterparts. Conclusions: Patients were generally more likely to use lifestyle-altering approaches to cope with treatment-related financial burden, but more than one-third adopted care-altering strategies. Younger patients and those with lower incomes were more likely to alter their care. Screening for and anticipating potentially harmful cost-coping behavior in the oncology clinic is important to reduce patient distress and promote optimal care. [Table: see text]

To date, the terms of the debate, occurring within scientific meetings and the literature, have focused on the presumed scientific necessity for mandatory research biopsies versus the rights of prospective trial participants to freely consider consent to a research biopsy separately from consent to a clinical trial. Proponents argue that some important scientific questions can only be addressed by evaluation of tumor tissue from all trial participants. They claim that in the era of molecular medicine, clinical researchers frequently need to understand not just who benefits or fails to benefit from a drug, but why benefit has occurred as assessed by whether the drug reached its intended target, and whether there are molecular factors that can predict response or guide further therapy. They assume that clinical samples will be unavailable or inappropriate to address some questions, that participation rates in optional research biopsies will be inadequate, and that biopsies can be conducted safely, with informed consent, and yield meaningful knowledge to advance the field. Opponents of mandatory research biopsies do not dispute the need for research biopsies in some settings. However, they argue that linking consent to a biopsy to trial participation is at minimum unfair, and at worst coercive. Access to promising, if unproven, experimental therapy within a trial is viewed by many as an important component of quality cancer care. It is clear that patients in some settings feel that they will be harmed, through loss of access to the experimental intervention, if they fail to pursue trial care. This arguably creates a sense of coercion that violates the principle of voluntarily informed consent to the research biopsy. Further, some trial participants mistakenly assume that all aspects of trial care and procedures are intended to provide direct clinical benefit. This therapeutic misconception complicates achieving informed consent in this setting. In addition, some argue that technical limitations in our ability to conduct meaningful correlative science make requirements for universal biopsies within a trial inappropriate at this time. Achievement of evaluable molecular analysis on all patients is rareevenwhenallarerequiredtoparticipate,andevaluationofasubsetof participants can be achieved through optional biopsies. The science, according to this view, should be improved before mandatory research biopsies are considered. It should be noted that no one supports asking trial participants to undergo a biopsy for research purposes in the absence of a strong scientific rationale, meaningful informed consent, and a low to minimal risk of expected complications. In addition, there is very little, if any, debate over trials that require a biopsy to guide management within the study, such as dose of a drug or choice of intervention, termed “integral biomarker” trials. Concerns arise when the purpose of the mandatory research biopsy is correlative science, or, most controversially, when a research biopsy is planned for purely exploratory purposes or for collection for future unspecified research. Acknowledged in most of the policy statements and position papers on this subject is a relative lack of data to inform discussions of the strength of the scientific rationale used to justify inclusion of mandatory research biopsies in a protocol, the quality of informed consent, participation rates and efficiency of accrual, safety, and outcomes of the procedures. Into this relative void, and a debate that at times brings more heat than light, step Overman et al, with a welcome report on the experience with mandatory research biopsies at a single institution over a recent 5-year period. The authors conducted a retrospective analysis of clinical trials contained in the MD Anderson interventional radiology database. They identified 19 clinical trials involving mandatory research biopsies conducted for purely correlative or exploratory purposes. For these trials, they reviewed the protocol, the informed consent document, and the medical record. Overman et al found that in the trial protocols the rationale for the biopsy was inconsistently explained and a statistical plan justifying the collectionofmandatorybiopsieswasfoundinonly30%oftrials involving correlativescience.Consentdocumentswerealsoproblematic.Only40% of informed consent documents for studies using mandatory research biopsies for correlative purposes explained the research nature of the biopsy, 70% explained the scientific rationale for the biopsy, and 30% addressed biopsy safety. With regard to safety, in analysis that included trials with optional biopsies and integral biomarker studies, the investigators reported an overall complication rate of 5.2% and a major complication rate (indicating need for hospitalization or surgery) of 0.8%. When considering intrathoracic and abdominal biopsies alone the overall complication rate rose to 9.8% with a major complication rate of 1.5%. They reported no biopsy-related deaths. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 1 JANUARY 1 2013

Purpose Young women with breast cancer often seek advice about whether treatment will affect their fertility. We sought to gain a better understanding of women’s attitudes about fertility and how these concerns affect decision making. Patients and Methods We developed a survey about fertility issues for young women with a history of early-stage breast cancer. The survey was e-mailed to all registered Young Survival Coalition survivor members (N = 1,702). E-mail reminders were used. Results Six hundred fifty-seven eligible respondents completed the survey. Mean age at breast cancer diagnosis was 32.9 years; mean current age was 35.8 years. Ninety percent of women were white; 62% were married; 76% were college graduates. Stages at diagnosis were as follows: 0, 10%; I, 27%; II, 47%; III, 13%. Sixty-two percent of women were within 2 years of diagnosis. Fifty-seven percent recalled substantial concern at diagnosis about becoming infertile with treatment. In multivariate logistic regression, greater concern about infertility was associated with wish for children/more children (odds ratio [OR], 120; P < .0001), number of prior pregnancies (OR, 0.78; P = .01), and prior difficulty conceiving (OR, 1.86; P = .08). Twenty-nine percent of women reported that infertility concerns influenced treatment decisions. Seventy-two percent of women reported discussing fertility concerns with their doctors; 51% felt their concerns were addressed adequately. Women seemed to overestimate their risk of becoming postmenopausal with treatment. Conclusion Fertility after treatment is a major concern for young women with breast cancer. There is a need to communicate with and educate young patients regarding fertility issues at diagnosis and a need for future research directed at preserving fertility for young breast cancer survivors.

Summary Background Many oncologists believe that patients with cancer who enrol in clinical trials have better outcomes than those who do not enrol. We aimed to assess the empirical evidence that such a trial effect exists. Methods We developed a conceptual framework for comparison of trial and non-trial patients. We then did a comprehensive literature search to identify studies that compared outcomes between these groups. We critically evaluated these studies to assess whether they provide valid and generalisable support for a trial effect. Findings We identified 26 comparisons, from 24 published articles, of outcomes among cancer patients enrolled and not enrolled in clinical trials. 21 comparisons used retrospective cohort designs. 14 comparisons provided some evidence that patients enrolled in trials have improved outcomes. However, strategies to control for potential confounding factors were inconsistent and frequently inadequate. Only eight comparisons restricted non-trial patients to those meeting trial eligibility criteria. Of these, three noted better outcomes in trial patients than in non-trial patients. Children with cancer, patients with haematological malignant disease, and patients treated before 1986 were disproportionately represented in positive studies. Interpretation Despite widespread belief that enrolment in clinical trials leads to improved outcomes in patients with cancer, there are insufficient data to conclude that such a trial effect exists. Until such data are available, patients with cancer should be encouraged to enrol in clinical trials on the basis of trials’ unquestioned role in improving treatment for future patients.

6559 Background: Patients with cancer are at risk for experiencing financial distress. Prior studies have indicated that objective financial burden follows trends associated with treatment course. However, little is known about whether patients’ subjective financial distress follows similar trends during the course of their treatment. The ability to predict risk of financial distress in relation to time on treatment may facilitate timing of interventions to alleviate financial distress. Methods: This was a cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about financial distress (via a validated measure) and out-of-pocket costs. Medical records were reviewed for disease and treatment data. We used the Spearman Rank Correlation Coefficient test and multivariable logistic regression to assess the correlation between months on treatment and fin...

QUESTION ASKED: Because the cost of oncologic care is perpetually rising, we wanted to know how often physicians who treat cancer discuss the cost of care (both out-of-pocket and societal) with their patients, what the nature of those discussions is, and whether such discussions affect treatment decisions. SUMMARY ANSWER: Sixty percent of responding physicians reported addressing costs frequently or always in clinic, 40% addressed costs rarely or never, and 36% did not believe it is the doctor’s responsibility to explain costs of care to patients. Additional responses are listed in Table 3 . The majority of physicians feel their patients are not well informed about costs. “I don’t know enough/lack of resources” is the largest reported barrier to cost discussions, and those who reported frequent discussions were significantly more likely to explain costs and to prioritize treatments in terms of cost. [Table: see text] METHODS: A 15-question, study-specific, self-administered anonymous survey was sent electronically to a randomly selected sample of 2,290 ASCO physician members. BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: Our overall response rate was somewhat low at 15%, with an adjusted response rate of 25% after adjusting for nonpracticing physician ASCO members. This increased the potential for selection bias, by which the respondents to this survey may not represent the true beliefs and practices of medical, radiation, and surgical oncologists. REAL-LIFE IMPLICATIONS: Our study offers a current snapshot of the frequency, nature, and attitudes toward cost discussions among medical, radiation, and surgical oncologists and their patients. Although the majority of responding physicians seem to agree that such discussions are legitimate—and arguably necessary—components of quality cancer care, there remains a substantial proportion who do not discuss costs nor feel it is their duty. Few believe they have adequate resources to discuss costs, suggesting that greater cost transparency, education concerning costs of care, tools to facilitate discussions, and validated interventions are needed.

1502 Background: The 2009 US Preventative Services Task Force (USPSTF) guidelines for breast cancer screening have proven controversial. Previously, annual screening was recommended for women over ...

6615 Background: Assuring treatment-related decision-making aligns with patients’ preferences is a critical component of quality care. Yet often patients’ preferred and actual treatment-related dec...

561 Background: Tamoxifen treated breast cancer patients with diminished CYP2D6 activity have lower endoxifen exposure, which may lead to inferior treatment outcomes. Increasing the daily tamoxifen...