Stephanie Melissa Smith

All Publications

• Minding the Gap for Survivors of Childhood Cancer. JAMA oncology Smith, S. M., Link, M. P., Effinger, K. E. 2020

  View details for DOI 10.1001/jamaoncol.2019.5556

  View details for PubMedID 31895404

• Barriers and facilitators of risk-based health care for adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Cancer Ford, J. S., Tonorezos, E. S., Mertens, A. C., Hudson, M. M., Casillas, J., Foster, B. M., Moskowitz, C. S., Smith, S. M., Chou, J. F., Buchanan, G., Robison, L. L., Oeffinger, K. C. 2019

  Abstract

  BACKGROUND: Optimal risk-based survivor health care includes surveillance for late effects and education targeted at reducing or preventing risky health behaviors. Understanding the reasons for a lack of risk-based follow-up care is essential.METHODS: Adult participants from the Childhood Cancer Survivor Study were surveyed about having a cancer-related visit in the past 2years and the likelihood of having a cancer-related visit in the future. Additional factors thought to be related to the primary outcomes were also assessed.RESULTS: Nine hundred seventy-five survivors completed the survey. Twenty-seven percent (95% confidence interval [CI], 24%-30%) had a cancer-related medical visit in the previous 2years, and 41% (95% CI, 38%-44%) planned to have such a visit within the next 2years. The likelihood of having had a cancer-related visit within the last 2years was higher among survivors assigning greater importance to these visits (relative risk [RR], 1.2; 95% CI, 1.1-1.3), perceiving greater susceptibility to health problems (RR, 1.2; 95% CI, 1.1-1.3), having a moderate to life-threatening chronic health problem related to their cancer (RR, 2.1; 95% CI, 1.7-2.7), seeing a primary care provider for a cancer-related problem (RR, 1.3; 95% CI, 1.0-1.6), having a cancer treatment summary (RR, 1.3; 95% CI, 1.0-1.6), and endorsing greater confidence in physicians' abilities to address questions and concerns (RR, 1.2; 95% CI, 1.0-1.3).CONCLUSIONS: Educational interventions improving awareness of treatment history and susceptibility to cancer-related late effects and corresponding risk-based care are likely to be beneficial for survivors of childhood cancers.

  View details for DOI 10.1002/cncr.32568

  View details for PubMedID 31626337

• Creating a Culture of Wellness in Residency. Academic medicine : journal of the Association of American Medical Colleges Edmondson, E. K., Kumar, A. A., Smith, S. M. 2018

  Abstract

  Despite increased awareness and recognition of the prevalence of physician burnout and the associated risks of depression and suicide, there is a paucity of actionable guidelines for residency programs to mitigate these risks for their residents. In this Invited Commentary, the authors acknowledge that, although there are inherent barriers to resident wellness, there are numerous modifiable barriers that present opportunities for programs to enable culture change and improve resident wellbeing. The authors frame the discussion with a personal narrative written by a resident in their internal medicine program who experienced burnout, depression, and suicidality during his intern year. They aim to inspire residency programs and hospital leadership to identify and intervene upon the modifiable barriers to wellness for residents in their programs in order to shape meaningful cultural change.

  View details for DOI 10.1097/ACM.0000000000002250

  View details for PubMedID 29668521

• Effect of Population Socioeconomic and Health System Factors on Medical Care of Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Caplin, D. A., Smith, K. R., Ness, K. K., Hanson, H. A., Smith, S. M., Nathan, P. C., Hudson, M. M., Leisenring, W. M., Robison, L. L., Oeffinger, K. C. 2017; 6 (1): 74?82

  Abstract

  To determine the independent contribution of population socioeconomic and health system factors on childhood cancer survivors' medical care and screening.7899 childhood cancer survivors in the United States and Canada enrolled in the Childhood Cancer Survivor Study (CCSS). Population-level factors were derived from U.S. Area Health Resource File or 201 Canadian Census. Health service utilization and individual-level factors were self-reported. Multivariable logistic regression was used to calculate the effect of population factors on medical care (any care vs. no care; risk-based care vs. general care) and indicated echocardiogram or mammogram, adjusting for individual sociodemographic and health status.After adjusting for individual factors, population factors had a nominal impact on childhood cancer survivors' medical care and screening. Higher population median income was associated with risk-based survivor-focused care versus general care (odds ratio [OR] 1.05, 95% confidence interval [CI], 1.01-1.09) among all participants, but not among U.S. residents only (OR 1.03, 95% CI, 0.99-1.07). For U.S. residents, the number of CCSS centers within the geographic area was associated with greater odds of receiving risk-based survivor-focused medical care (OR 1.12, 95% CI, 1.04-1.20). Areas with higher median income had higher rates of echocardiogram screening among survivors at risk of cardiomyopathy (for every $10,000 increase in median income, there is a 12% increase in odds of echocardiogram screening; 95% CI 1.05-1.20). A positive relationship was identified between greater number of physicians and surgeons in the county of residence and recommended echocardiogram (for every additional 1000 physicians and surgeons: OR 1.12, 95% CI, 1.01-1.23). We found no association between population-level factors and mammography screening.Population socioeconomic disparities moderately affect childhood cancer survivors' risk-based medical care and screening after accounting for individual sociodemographic and health factors.

  View details for DOI 10.1089/jayao.2016.0016

  View details for Web of Science ID 000395765800009

  View details for PubMedID 27754726

  View details for PubMedCentralID PMC5346913

• Exercise intensity in cancer survivors: A matter of the heart Cardio-Oncology Smith, S. M., Carver, J. R. 2017; 3

  View details for DOI 10.1186/s40959-017-0022-x

• Web Exclusives. Annals Story Slam - A Long Stay. Annals of internal medicine Smith, S. 2017; 167 (12): SS1

  View details for DOI 10.7326/W17-0075

  View details for PubMedID 29255880

• Health Care Utilization, Lifestyle, and Emotional Factors and Mammography Practices in the Childhood Cancer Survivor Study CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Rosenberg, S. M., Moskowitz, C. S., Ford, J. S., Henderson, T. O., Frazier, A. L., Diller, L. R., Hudson, M. M., Stanton, A. L., Chou, J. F., Smith, S., Leisenring, W. M., Mertens, A. C., Cox, C. L., Nathan, P. C., Krull, K. R., Robison, L. L., Oeffinger, K. C. 2015; 24 (11): 1699-1706

  Abstract

  Women with a history of chest radiotherapy have an increased risk of breast cancer; however, many do not undergo annual recommended screening mammography. We sought to characterize the relationship between mammography and potentially modifiable factors, with the goal of identifying targets for intervention to improve utilization.Of 625 female participants sampled from the Childhood Cancer Survivor Study, who were treated with chest radiotherapy, 551 responded to a survey about breast cancer screening practices. We used multivariate Poisson regression to assess several lifestyle and emotional factors, health care practices, and perceived breast cancer risk, in relation to reporting a screening mammogram within the last two years.Women who had a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI) 1.26-2.49], and who perceived their breast cancer risk as higher than the average woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09-1.46). We detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52-0.95)] on having a mammogram among older women compared with younger women. Smoking, obesity, physical activity, coping, and symptoms of depression and somatization were not associated with mammographic screening.Our findings suggest that compliance with routine and risk-based screening can be an important indicator of mammography in childhood cancer survivors. In addition, there is a need to ensure women understand their increased breast cancer risk, as a means to encouraging them to follow breast surveillance guidelines.Screening encounters could be used to promote mammography compliance in this population.

  View details for DOI 10.1158/1055-9965.EPI-14-1377

  View details for Web of Science ID 000365598600008

  View details for PubMedID 26304504

  View details for PubMedCentralID PMC4633330

• Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia PEDIATRIC BLOOD & CANCER Tonorezos, E. S., Snell, P. G., Moskowitz, C. S., Eshelman-Kent, D. A., Liu, J. E., Chou, J. F., Smith, S. M., Dunn, A. L., Church, T. S., Oeffinger, K. C. 2013; 60 (8): 1358-1364

  Abstract

  Adult survivors of childhood acute lymphoblastic leukemia (ALL) are at increased cardiovascular risk. Studies of factors including treatment exposures that may modify risk of low cardiorespiratory fitness in this population have been limited.To assess cardiorespiratory fitness, maximal oxygen uptake (VO2 max) was measured in 115 ALL survivors (median age, 23.5 years; range 18-37). We compared VO2 max measurements for ALL survivors to those estimated from submaximal testing in a frequency-matched (age, gender, race/ethnicity) 2003-2004 National Health and Nutritional Examination Survey (NHANES) cohort. Multivariable linear regression models were constructed to evaluate the association between therapeutic exposures and outcomes of interest.Compared to NHANES participants, ALL survivors had a substantially lower VO2 max (mean 30.7 vs. 39.9 ml/kg/min; adjusted P < 0.0001). For any given percent total body fat, ALL survivors had an 8.9 ml/kg/min lower VO2 max than NHANES participants. For key treatment exposure groups (cranial radiotherapy [CRT], anthracycline chemotherapy, or neither), ALL survivors had substantially lower VO2 max compared with NHANES participants (all comparisons, P < 0.001). Almost two-thirds (66.7%) of ALL survivors were classified as low cardiorespiratory fitness compared with 26.3% of NHANES participants (adjusted P < 0.0001). In multivariable models including only ALL survivors, treatment exposures were modestly associated with VO2 max. Among females, CRT was associated with low VO2 max (P = 0.02), but anthracycline exposure was not (P = 0.58). In contrast, among males, anthracycline exposure ? 100 mg/m(2) was associated with low VO2 max (P = 0.03), but CRT was not (P = 0.54).Adult survivors of childhood ALL have substantially lower levels of cardiorespiratory fitness compared with a similarly aged non-cancer population.

  View details for DOI 10.1002/pbc.24492

  View details for Web of Science ID 000320399800025

  View details for PubMedID 23418044

  View details for PubMedCentralID PMC3725590

• Acute Cardiovascular Toxicity of Low-Dose Intrathecal Ziconotide. Pain medicine (Malden, Mass.) Heifets, B. D., Smith, S. M., Leong, M. S. 2013

  View details for PubMedID 23855951

• A feasibility study to evaluate breast cancer patients' knowledge of their diagnosis and treatment PATIENT EDUCATION AND COUNSELING Smith, S. M., Balise, R. R., Norton, C., Chen, M. M., Flesher, A. N., Guardino, A. E. 2012; 89 (2): 321-329

  Abstract

  To evaluate the feasibility of an electronic survey to assess patients' knowledge of their breast cancer and treatment, and interest in receiving a medical summary.Women undergoing breast cancer treatment completed an interviewer-administered electronic survey in person or by telephone. Medical records were abstracted to evaluate knowledge accuracy.Among 38 eligible patients approached for the study, 35 (92%) participated and 33 (94%) completed the survey. Participants' perceived knowledge tended to be greater than their actual knowledge. Reporting of clinicopathologic features was most accurate for stage (91%) and lymph node status (88%), and least accurate for tumor size (61%), type (61%), and grade (33%). Accurate reporting of tumor receptor over-expression varied from 76% (estrogen receptor) to 39% (progesterone receptor). Many patients correctly recalled general treatment modalities and details of surgery; fewer recalled details of radiation and chemotherapy. Importantly, nearly all (32/33) were interested in receiving a breast cancer medical summary.An electronic survey is feasible to assess breast cancer patients' knowledge. This data suggest that patients have gaps in knowledge and would like a personalized medical summary.Larger studies are needed to validate and characterize knowledge gaps, and test interventions to improve physician-patient information sharing.

  View details for DOI 10.1016/j.pec.2012.08.015

  View details for Web of Science ID 000311766700016

  View details for PubMedID 23031612

  View details for PubMedCentralID PMC5310250

• Increasing Rates of Breast Cancer and Cardiac Surveillance Among High-Risk Survivors of Childhood Hodgkin Lymphoma Following a Mailed, One-Page Survivorship Care Plan PEDIATRIC BLOOD & CANCER Oeffinger, K. C., Hudson, M. M., Mertens, A. C., Smith, S. M., Mitby, P. A., Eshelman-Kent, D. A., Ford, J. S., Jones, J. K., Kamani, S., Robison, L. L. 2011; 56 (5): 818-824

  Abstract

  Hodgkin lymphoma (HL) survivors face substantially elevated risks of breast cancer and cardiovascular disease. They and their physicians are often unaware of these risks and surveillance recommendations.A prospective one-arm study was conducted among a random sample of 72 HL survivors, ages 27-55 years, participating in the Childhood Cancer Survivor Study (CCSS) who were at increased risk for breast cancer and/or cardiomyopathy and had not had a screening mammogram or echocardiogram, respectively, within the prior 2 years. A one-page survivorship care plan with recommendations for surveillance was mailed to participants. In addition, survivors' primary physicians were contacted and provided patient-specific information and a web-based Virtual Information Center was made available for both survivors and physicians. Outcomes were assessed by telephone 6 months after the intervention.The survivor participation (62/72; 86%) and 6-month retention (56/61; 92%) rates were high. Tension and anxiety, measured by the Profile of Mood States, did not increase following risk notification; 91% of survivors described their reactions to receiving the information in positive terms. At 6 months, 41% of survivors reported having completed the recommended mammogram; 20% reported having an echocardiogram (females 30%, males 10%). Only 29% of survivors visited the website. Nine physicians enrolled, and none used the study resources.A mailed, personalized survivorship care plan was effective in communicating risk and increasing compliance with recommended medical surveillance. Internet- and telephone-based strategies to communicate risk were not utilized by survivors or physicians.

  View details for DOI 10.1002/pbc.22696

  View details for Web of Science ID 000288132100020

  View details for PubMedID 21370417

• Inconsistent mammography perceptions and practices among women at risk of breast cancer following a pediatric malignancy: a report from the Childhood Cancer Survivor Study CANCER CAUSES & CONTROL Smith, S. M., Ford, J. S., Rakowski, W., Moskowitz, C. S., Diller, L., Hudson, M. M., Mertens, A. C., Stanton, A. L., Henderson, T. O., Leisenring, W. M., Robison, L. L., Oeffinger, K. C. 2010; 21 (10): 1585-1595

  Abstract

  Women treated with chest radiation for a pediatric cancer have low mammography screening rates despite their high risk for breast cancer. This study characterized the relationship between perceptions of mammography and screening practices. A cross-sectional survey was administered to 523 women in North America who were treated with chest radiation before 21 years of age. Women with inconsistent mammography perceptions and practices were identified using the Pros and Cons of Mammography for perceptions and Transtheoretical Model stages of adoption for prior and intended screening practices. Classification and regression tree (CART) analysis was used to identify barriers to and facilitators of screening among women with positive and negative perceptions. Nearly one-third of the cohort had inconsistent perceptions and practices: 37.4% had positive perceptions and were not having mammograms; 27.6% had negative/neutral perceptions and were having mammograms. Regardless of perceptions, a recent physician's recommendation for mammography, age ? 40, and interest in routine health care were universally associated with mammography practices. For women with positive perceptions and a physician's recommendation, barriers to screening included high acceptance coping, low active-planning coping, and high internal health locus of control. For women with negative perceptions, acknowledging the importance of asymptomatic screening was associated with mammography.

  View details for DOI 10.1007/s10552-010-9587-5

  View details for Web of Science ID 000281934800006

  View details for PubMedID 20506037

  View details for PubMedCentralID PMC2941535

• Long-term Survivors of Childhood Ewing Sarcoma: Report From the Childhood Cancer Survivor Study JOURNAL OF THE NATIONAL CANCER INSTITUTE Ginsberg, J. P., Goodman, P., Leisenring, W., Ness, K. K., Meyers, P. A., Wolden, S. L., Smith, S. M., Stovall, M., Hammond, S., Robison, L. L., Oeffinger, K. C. 2010; 102 (16): 1272-1283

  Abstract

  The survival of Ewing sarcoma (ES) patients has improved since the 1970s but is associated with considerable future health risks.The study population consisted of long-term (> or =5-year) survivors of childhood ES diagnosed before age 21 from 1970 to 1986. Cause-specific mortality was evaluated in eligible survivors (n = 568), and subsequent malignant neoplasms, chronic health conditions, infertility, and health status were evaluated in the subset participating in the Childhood Cancer Survivor Study (n = 403). Outcomes were compared with the US population and sibling control subjects (n = 3899). Logistic, Poisson, or Cox proportional hazards models, with adjustments for sex, age, race/ethnicity, and potential intrafamily correlation, were used. Statistical tests were two-sided.Cumulative mortality of ES survivors was 25.0% (95% confidence interval [CI] = 21.1 to 28.9) 25 years after diagnosis. The all-cause standardized mortality ratio was 13.3 (95% CI = 11.2 to 15.8) overall, 23.1 (95% CI = 17.6 to 29.7) for women, and 10.0 (95% CI = 7.9 to 12.5) for men. The nonrecurrence-progression non-external cause standardized mortality ratio (subsequent non-ES malignant neoplasms and cardiac and pulmonary causes potentially attributable to ES treatment) was 8.7 (95% CI = 6.2 to 12.0). Twenty-five years after ES diagnosis, cumulative incidence of subsequent malignant neoplasms, excluding nonmelanoma skin cancers, was 9.0% (95% CI = 5.8 to 12.2). Compared with siblings, survivors had an increased risk of severe, life-threatening, or disabling chronic health conditions (relative risk = 6.0, 95% CI = 4.1 to 9.0). Survivors had lower fertility rates (women: P = .005; men: P < .001) and higher rates of moderate to extreme adverse health status (P < .001).Long-term survivors of childhood ES exhibit excess mortality and morbidity.

  View details for DOI 10.1093/jnci/djq278

  View details for Web of Science ID 000281182500011

  View details for PubMedID 20656964

  View details for PubMedCentralID PMC2948841

• Systematic Review: Surveillance for Breast Cancer in Women Treated With Chest Radiation for Childhood, Adolescent, or Young Adult Cancer ANNALS OF INTERNAL MEDICINE Henderson, T. O., Amsterdam, A., Bhatia, S., Hudson, M. M., Meadows, A. T., Neglia, J. P., Diller, L. R., Constine, L. S., Smith, R. A., Mahoney, M. C., Morris, E. A., Montgomery, L. L., Landier, W., Smith, S. M., Robison, L. L., Oeffinger, K. C. 2010; 152 (7): 444?W154

  Abstract

  Women treated with therapeutic chest radiation may develop breast cancer.To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer.Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008).Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation?Three investigators independently extracted data and assessed study quality.Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited.The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size.Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance.

  View details for DOI 10.7326/0003-4819-152-7-201004060-00009

  View details for Web of Science ID 000276386900005

  View details for PubMedID 20368650

  View details for PubMedCentralID PMC2857928

• Knowledge of Hepatitis C Virus Screening in Long-Term Pediatric Cancer Survivors A Report From the Childhood Cancer Survivor Study CANCER Lansdale, M., Castellino, S., Marina, N., Goodman, P., Hudson, M. M., Mertens, A. C., Smith, S. M., Leisenring, W., Robison, L. L., Oeffinger, K. C. 2010; 116 (4): 974-982

  Abstract

  Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV.To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986.More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment-related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5-1.0).Many pediatric cancer survivors at risk for transfusion-acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening.

  View details for DOI 10.1002/cncr.24810

  View details for Web of Science ID 000274315800027

  View details for PubMedID 20041485

  View details for PubMedCentralID PMC2819650

• Stathmin and Tubulin Expression and Survival of Ovarian Cancer Patients Receiving Platinum Treatment With and Without Paclitaxel CANCER Su, D., Smith, S. M., Preti, M., Schwartz, P., Rutherford, T. J., Menato, G., Danese, S., Ma, S., Yu, H., Katsaros, D. 2009; 115 (11): 2453?63

  Abstract

  Paclitaxel interacts with microtubules to exert therapeutic effects. Molecules that affect microtubule activity, such as betaIII-tubulin and stathmin, may interfere with the treatment. In this study, the authors analyzed betaIII-tubulin and stathmin expression in ovarian tumors and examined their associations with treatment response and patient survival.The study included 178 patients with epithelial ovarian cancer who underwent cytoreductive surgery followed by platinum-based chemotherapy; of these patients, 75 also received paclitaxel. Fresh tumor samples that were collected at surgery were analyzed for messenger RNA expression of betaIII-tubulin and stathmin using real-time polymerase chain reaction analysis. Associations of these molecules with treatment response, disease progression, and overall survival were evaluated.High stathmin expression was associated with worse disease progression-free and overall survival compared with low stathmin expression. This association was independent of patient age, disease stage, tumor grade, histology, and residual tumor size and was observed in patients who received platinum plus paclitaxel, but not in patients who received platinum without paclitaxel, suggesting that stathmin expression in tumor tissue may interfere with paclitaxel treatment. Similar effects were not observed for betaIII-tubulin, although high betaIII-tubulin expression was associated with disease progression among patients who received platinum without paclitaxel. No associations were observed between treatment response and tubulin or stathmin expression. Expression levels of betaIII-tubulin and stathmin were correlated significantly.High stathmin expression predicted an unfavorable prognosis in patients with ovarian cancer who received paclitaxel and platinum chemotherapy. This finding supports the possibility that stathmin may interfere with paclitaxel treatment, leading to a poor prognosis for patients with ovarian cancer.

  View details for DOI 10.1002/cncr.24282

  View details for Web of Science ID 000266300200012

  View details for PubMedID 19322891

• Peptide concentrations and mRNA expression of IGF-I, IGF-II and IGFBP-3 in breast cancer and their associations with disease characteristics BREAST CANCER RESEARCH AND TREATMENT Mu, L., Katsaros, D., Wiley, A., Lu, L., de la Longrais, I. A., Smith, S., Khubchandani, S., Sochirca, O., Arisio, R., Yu, H. 2009; 115 (1): 151-162

  Abstract

  To measure peptide concentrations and mRNA expression of the IGF Family in breast cancer and to examine their associations with the disease features.Fresh tumor samples were collected from 348 patients who underwent surgery for breast cancer. Tissue levels of mRNA and peptide of IGF-I, IGF-II, and IGFBP-3 were analyzed with real-time RT-PCR and ELISA, respectively. Cox proportional hazards regression model was used to examine the associations of IGF markers with patient survival.Age was inversely associated with IGF-I, IGF-II and IGFBP-3 at both mRNA and peptide levels. Small tumors, early TNM stages, or low grades were associated with high mRNA expression of IGFs and IGFBP-3. Hormone receptors were positively correlated with IGF-I and IGF-II expression. Survival analysis showed that patients with high expression of one of the IGF-I transcripts, IGF-IA, had lower risk of disease recurrence (HR = 0.47, 95%CI: 0.27-0.81) and death (HR = 0.35, 95%CI: 0.18-0.70) compared to those with low expression. High IGFBP-3 expression was also inversely associated with reduced risk of death (HR = 0.47, 95%CI: 0.23-0.95). Similar associations, however, were not observed when tissue levels of IGF-I peptide or IGFBP-3 protein were analyzed. High IGF-II peptide was related to increased risk of relapse (HR = 1.91, 95%CI: 1.12-3.27).Our findings of high mRNA expression of IGFs and IGFBP-3 being associated with less aggressive tumors and favorable prognosis were consistent with previous observations, but were not supported by the measurement of tissue levels of IGF-I peptide and IGFBP-3 protein, suggesting that IGF mRNA expression and tissue levels of IGF peptides are regulated by different mechanisms and assessing these molecules in tumor tissue may have different implications.

  View details for DOI 10.1007/s10549-008-0046-x

  View details for Web of Science ID 000265440400017

  View details for PubMedID 18481170

• Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Oeffinger, K. C., Ford, J. S., Moskowitz, C. S., Diller, L. R., Hudson, M. M., Chou, J. F., Smith, S. M., Mertens, A. C., Henderson, T. O., Friedman, D. L., Leisenring, W. M., Robison, L. L. 2009; 301 (4): 404-414

  Abstract

  Women treated with chest radiation for a pediatric malignancy have a significantly increased risk of breast cancer at a young age and are recommended to have an annual screening mammogram starting at age 25 years or 8 years after radiation, whichever occurs last.To characterize the breast cancer surveillance practices among female pediatric cancer survivors who were treated with chest radiation and identify correlates of screening.Between June 2005 and August 2006, a 114-item questionnaire was administered to a random sample of 625 women aged 25 through 50 years who had survived pediatric cancer, who had been treated with chest radiation, and who were participating in the Childhood Cancer Survivor Study (CCSS), a North American cohort of long-term survivors diagnosed from 1970-1986. Comparisons were made with similarly aged pediatric cancer survivors not treated with chest radiation (n = 639) and the CCSS siblings cohort (n = 712).Screening mammogram within the previous 2 years.Of 1976 cancer survivors and siblings who were contacted, 87.9% participated. Among the 551 women with a history of chest radiation, 55% reported a screening mammogram in the past 2 years (ages 25-39 years, 36.5%; 95% confidence interval [CI], 31.0%-42.0%; ages 40-50 years, 76.5%; 95% CI, 71.3%-81.7%). In comparison, 40.5% of survivors without chest radiation and 37.0% of CCSS siblings reported a screening mammogram in the same time interval. Notably, among women with a history of chest radiation, 47.3% (95% CI; 41.6%-53.0%) of those younger than 40 years had never had a mammogram and only 52.6% (95% CI; 46.4%-58.8%) of women aged 40 through 50 years were being regularly screened (2 mammograms within 4 years). Screening rates were higher among women who reported a physician recommendation than those who did not (ages 25-39 years, 76.0% vs 17.6%; ages 40-50 years, 87.3% vs 58.3%). In multivariate models, the association was particularly strong for younger women (ages 25-39 years, prevalence ratio [PR], 3.0; 95% CI, 2.0-4.0; ages 40-50 years, PR, 1.3; 95% CI, 1.1-1.6).In this cohort of women who had childhood cancer treated with chest radiation, 63.5% of those aged 25 through 39 years and 23.5% of those aged 40 through 50 years had not had mammography screening for breast cancer within the previous 2 years despite a guideline recommendation that survivors of childhood cancer who were treated with chest radiation should undergo annual screening mammography.

  View details for Web of Science ID 000262777200020

  View details for PubMedID 19176442

• ERCC1 genotype and phenotype in epithelial ovarian cancer identify patients likely to benefit from paclitaxel treatment in addition to platinum-based therapy JOURNAL OF CLINICAL ONCOLOGY Smith, S., Su, D., de la Longrais, I. A., Schwartz, P., Puopolo, M., Rutherford, T. J., Mor, G., Yu, H., Katsaros, D. 2007; 25 (33): 5172-5179

  Abstract

  To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel.Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival.Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance.Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.

  View details for DOI 10.1200/JCO.2007.11.8547

  View details for Web of Science ID 000251074400008

  View details for PubMedID 18024864

• Genetic polymorphisms and treatment response in advanced non-small cell lung cancer LUNG CANCER Su, D., Ma, S., Liu, P., Jiang, Z., Lv, W., Zhang, Y., Deng, Q., Smith, S., Yu, H. 2007; 56 (2): 281-288

  Abstract

  Genetic polymorphisms involved in DNA repair and apoptosis are suspected to influence patient response to cancer treatment. To evaluate the effect of genetic variations on chemotherapy and/or radiotherapy, we genotyped four single nucleotide polymorphisms (SNPs) in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu), and iASPP (A67T), and examined their associations with treatment response among patients with advanced non-small cell lung cancer (NSCLC).Included in the study were 230 patients diagnosed with inoperable advanced NSCLC. Of these patients, 76 received platinum-based chemotherapy, 125 received chemotherapy plus radiation, and 29 received radiotherapy only. The SNPs were genotyped using the TaqMan methods.Among the patients who received chemotherapy only, ERCC1 (Asn118Asn) genotype was significantly associated with treatment response. Patients with either one or two T alleles (T/T+C/T) at Asn118Asn were more likely not to respond to platinum-based chemotherapy compared to those without the T allele (OR=4.10, 95% CI: 1.31-12.85). For patients who were treated with both chemotherapy and radiotherapy, treatment response seemed to differ substantially between patients with different genotypes of iASPP (A67T). Patients carrying an A allele (A/T+A/A) at A67T were more likely to respond to combined chemotherapy and radiotherapy compared to those not carrying the A allele (OR=0.25, 95% CI: 0.08-0.74). An association with treatment response was also suggested for the selected polymorphism in APE1, but no association was found for the ATM polymorphism.We found that SNPs in ERCC1 and iASPP were associated with response to chemotherapy or combined chemotherapy and radiotherapy in NSCLC patients. These findings support the notion that genetic variations related to DNA repair or apoptosis may affect the effect of chemotherapy or radiation on NSCLC.

  View details for DOI 10.1016/j.lungcan.2006.12.002

  View details for Web of Science ID 000246779600018

  View details for PubMedID 17222938