Publications by authors named "Patricia A Ganz"

424 Publications

The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

Genet Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.

Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.

Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS and CBC risk.

Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.

Conclusion: The PRS can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
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http://dx.doi.org/10.1038/s41436-021-01198-7DOI Listing
June 2021

Adjuvant Olaparib for Patients with - or -Mutated Breast Cancer.

N Engl J Med 2021 Jun 3. Epub 2021 Jun 3.

From the Breast Cancer Now Toby Robins Research Centre, the Institute of Cancer Research (A.N.J.T.), and the Breast Cancer Now Unit, Guy's Hospital Cancer Centre, King's College London (A.N.J.T.), London, AstraZeneca, Cambridge (S.J.H., N.B.), and Frontier Science (Scotland), Kincraig (R.M.C., E.M.F., C.C.) - all in the United Kingdom; Dana-Farber Cancer Institute, Harvard Medical School (J.E.G., R.D.G.), Frontier Science Foundation (R.D.G.), and Harvard T.H. Chan School of Public Health (R.D.G.) - all in Boston; the Breast Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (B.K.); the University of Milan, European Institute of Oncology IRCCS, Milan (G.V.); Breast International Group (D.F., A.A.) and Institut Jules Bordet, l'Université Libre de Bruxelles (E.A., M.P.), Brussels; NRG Oncology (P.R., H.B., P.C.L., N.W., G.Y., C.E.G.) and the Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania (S.M.D.), Philadelphia, and the UPMC Hillman Cancer Center (P.R., P.C.L., N.W.) and the Department of Biostatistics (H.B., J.P.C., G.Y.), University of Pittsburgh, and the NSABP Foundation (N.W.), Pittsburgh - all in Pennsylvania; AstraZeneca, Gaithersburg (A.F.), and the National Cancer Institute, Rockville (L.A.K.) - both in Maryland; Vall d'Hebron Institute of Oncology and Vall d'Hebron University Hospital (J.B.) - both in Barcelona; BC Cancer, Vancouver, BC, Canada (K.A.G.); Sahlgrenska University Hospital (B.L.) and the Institute of Clinical Sciences, Department of Oncology, Sahlgrenska Academy, Gothenburg University (B.L.) - both in Gothenburg, Sweden; the Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk (E.S.), the Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw (Z.N.), the International Hereditary Cancer Center, Pomeranian Medical University, Szczecin (T.H.), and Read-Gene, Grzepnica (T.H.) - all in Poland; Kaiser Permanente Vallejo Medical Center, Vallejo (J.M.S.), and the UCLA Fielding School of Public Health, David Geffen School of Medicine at UCLA (P.A.G.), and the UCLA Jonsson Comprehensive Cancer Center (P.A.G.), Los Angeles - all in California; Fudan University Shanghai Cancer Center, Shanghai, China, (Z.S.); Georgia NCORP, Northside Hospital Cancer Institute (A.W.P.), and Piedmont Healthcare (A.W.P.) - both in Atlanta; German Breast Group, Neu-Isenburg (S.L.), the Center for Hematology and Oncology Bethanien and Goethe University, Frankfurt (S.L.), and the Center for Familial Breast and Ovarian Cancer and the Center for Integrated Oncology, Faculty of Medicine, University Hospital Cologne, Cologne (R.S.) - all in Germany; the Department of Internal Medicine I and Gaston H. Glock Research Center, Medical University of Vienna, Vienna (G.G.S.); Merck, Kenilworth, NJ (V.K.); the University of Queensland Centre for Clinical Research and Pathology Queensland (S.R.L.) - both in Brisbane, QLD, Australia; and Houston Methodist Cancer Center (C.E.G.) and Weill Cornell Medical College (C.E.G.) - both in Houston.

Background: Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with or germline mutation-associated early breast cancer.

Methods: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with or germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival.

Results: A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest.

Conclusions: Among patients with high-risk, HER2-negative early breast cancer and germline or pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).
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http://dx.doi.org/10.1056/NEJMoa2105215DOI Listing
June 2021

NRG Oncology/NSABP B-47 menstrual history study: impact of adjuvant chemotherapy with and without trastuzumab.

NPJ Breast Cancer 2021 May 20;7(1):55. Epub 2021 May 20.

NSABP/NRG Oncology, Pittsburgh, PA, USA.

The NRG Oncology/NSABP B-47 menstrual history (MH) study examined trastuzumab effects on menstrual status and associated circulating reproductive hormones. MH was evaluated by questions related to hysterectomy, oophorectomy, and reported menstrual changes. Pre/perimenopausal women were assessed at entry, 3, 6, 12, 18, 24, 30, and 36 months. Consenting women had estradiol and FSH measurement at entry, 3, 6, 12, 18, and 24 months. Logistic regression determined predictors of amenorrhea and hormone levels at 12, 24, and 36 months. Between 2/8/2011 and 2/10/2015, 3270 women with node-positive/high-risk node-negative HER2-low breast cancer were enrolled. There were 1,458 women enrolled in the MH study; 1231 consented to baseline blood samples. Trastuzumab did not contribute to a higher amenorrhea rate. Amenorrhea predictors were consistent with earlier studies; however, to our knowledge, this is the largest prospective study to include serial reproductive hormone measurements to 24 months and clinical amenorrhea reports to 36 months. These data can help to counsel patients regarding premature menopause risk.
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http://dx.doi.org/10.1038/s41523-021-00264-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137688PMC
May 2021

The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age.

Cancer Epidemiol Biomarkers Prev 2021 Jun 26;30(6):1241-1249. Epub 2021 Mar 26.

Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.

Background: Estrogens are thought to contribute to breast cancer risk through cell cycling and accelerated breast aging. We hypothesize that lifetime estrogen exposure drives early epigenetic breast aging observed in healthy women. In this study, we examined associations between hormonal factors and epigenetic aging measures in healthy breast tissues.

Methods: We extracted DNA from breast tissue specimens from 192 healthy female donors to the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Methylation experiments were performed using the Illumina EPIC 850K array platform. Age-adjusted regression models were used to examine for associations between factors related to estrogen exposure and five DNA methylation-based estimates: Grim age, pan-tissue age, Hannum age, phenotypic age, and skin and blood clock age.

Results: Women were aged 19-90 years, with 95 premenopausal, and 97 nulliparous women. The age difference (Grim age - chronologic age) was higher at earlier ages close to menarche. We found significant associations between earlier age at menarche and age-adjusted accelerations according to the Grim clock, the skin and blood clock, and between higher body mass index (BMI) and age-adjusted accelerations in the Grim clock, Hannum clock, phenotypic clock, and skin and blood clock.

Conclusions: Earlier age at menarche and higher BMI are associated with elevations in DNA methylation-based age estimates in healthy breast tissues, suggesting that cumulative estrogen exposure drives breast epigenetic aging.

Impact: Epigenetic clock measures may help advance inquiry into the relationship between accelerated breast tissue aging and an elevated incidence of breast cancer in younger women.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172523PMC
June 2021

A qualitative study to evaluate physician attitudes regarding omission of surgery among exceptional responders to neoadjuvant systemic therapy for breast cancer (NRG-CC006).

Breast Cancer Res Treat 2021 Jun 19;187(3):777-784. Epub 2021 Mar 19.

Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, USA.

Purpose: Accrual to clinical trials that challenge well-established treatment paradigms represents a unique challenge. Physician opinions on investigation of a novel approach to breast cancer treatment, in which patients with complete response to neoadjuvant chemotherapy are offered omission of lumpectomy, are unknown. NRG-CC006 sought to describe physician attitudes toward a novel approach to breast cancer treatment.

Methods: We recruited 18 participants in the fields of surgery, medical oncology, and radiation oncology to participate in the semi-structured telephone interviews. Main outcomes are qualitative themes associated with omission of surgery.

Results: Of 18 interview participants, specialty and gender were evenly represented across surgery, medical oncology, and radiation oncology. Qualitative themes included general attitudes toward treatment de-escalation, stakeholder considerations, and trial/protocol considerations. The vast majority of participants expressed interest in investigation of omission of surgery, with all participants endorsing need for further investigation into treatment de-escalation. Stakeholder considerations in opening such a trial emphasized need for multidisciplinary involvement and, particularly, the unique role of surgeons as gatekeepers in breast cancer treatment. Finally, participants endorsed a need for further foundational studies to develop ways to predict complete pathologic response to chemotherapy without surgical intervention.

Conclusions: Physicians expressed interest in investigating a novel approach to breast cancer treatment that would omit surgery in complete responders to neoadjuvant chemotherapy. Multidisciplinary input, and specifically surgeon engagement, will be key to the success of future investigations. Ongoing work to develop approaches to predict pathologic complete response accurately is needed to achieve the promise of this idea. ClinTrials #: BR005: NCT03188393 June 13, 2017.
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http://dx.doi.org/10.1007/s10549-021-06172-0DOI Listing
June 2021

Vulnerability to inflammation-related depressive symptoms: Moderation by stress in women with breast cancer.

Brain Behav Immun 2021 05 9;94:71-78. Epub 2021 Mar 9.

Department of Psychology, UCLA, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, United States; Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, United States.

Background: Stress precipitates depression and may do so in part by increasing susceptibility to inflammation-induced depressive symptoms. However, this has not been examined among individuals facing a major life stressor. Accordingly, the present study tested the moderating role of stress on the longitudinal association between inflammation and depressive symptoms among women with breast cancer.

Methods: Women recently diagnosed with early-stage breast cancer (N = 187) were enrolled before starting adjuvant/neoadjuvant treatment. Blood draws and self-reported depressive symptoms were collected pre-treatment, post-treatment, and at 6, 12, and 18-month post-treatment follow ups. C-reactive protein (CRP) was used to index inflammation. Measures of psychological stress, including cancer-related stress, general stress perceptions, and childhood stress, were administered pre-treatment.

Results: Stress moderated the association between CRP and depressive symptoms, such that higher levels of CRP were associated with elevated depressive symptoms only among women who reported high cancer-related stress (β = 0.080, p = .002) and perceived stress (β = 0.053, p = .044); childhood stress effects were non-significant. Moreover, elevated CRP was associated with increased odds of exhibiting clinically significant depressive symptoms (OR = 1.64, p < .001) among women who reported high cancer-related stress. Results were independent of age, BMI, race and cancer-related covariates.

Conclusions: Stress was found to heighten sensitivity to inflammation-associated depressive symptoms over a 2-year period, with notably stronger effects for subjective stress responses to a concurrent life event. Individuals who are most distressed following a major life event may exhibit the greatest risk for inflammation-induced depression.
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http://dx.doi.org/10.1016/j.bbi.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058308PMC
May 2021

Executive Functioning and Depressive Symptoms After Cancer: The Mediating Role of Coping.

Psychosom Med 2021 Apr;83(3):291-299

From the Department of Psychology (Radin, Stanton, Bower), Schools of Medicine and Public Health (Ganz), Jonsson Comprehensive Cancer Center (Ganz, Van Dyk, Stanton, Bower), Department of Psychiatry and Biobehavioral Sciences (Van Dyk, Stanton, Bower), and Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior (Stanton, Bower), University of California, Los Angeles, Los Angeles, California.

Objective: Cognitive difficulties are a common complaint among patients with breast cancer and may adversely affect psychological well-being. In particular, problems with executive functioning (EF) may interfere with coping, which is known to influence depressive symptoms. The current study was designed to examine correlations between EF, coping, and depressive symptoms in breast cancer survivors and to longitudinally test the hypothesis that coping mediates the relationship between EF and depressive symptoms.

Methods: Participants included 171 women with early-stage breast cancer assessed at the end of primary treatment with surgery, radiation, and/or chemotherapy and at 6 months, 1 year, and 2 years after treatment follow-ups as part of the Mind-Body Study. Participants completed questionnaires to assess subjective EF, approach and avoidant coping, and depressive symptoms, and neuropsychological testing was conducted to assess objective EF. Bivariate correlations were used to examine associations between EF, coping, and depressive symptoms. Mediation analyses were conducted using a bootstrapping approach (PROCESS).

Results: At 1 year after treatment, objective and subjective EFs were correlated with avoidant coping (r = -0.172 [p = .024] and r = 0.297 [p < .001], respectively). In longitudinal analyses, use of the avoidant strategy behavioral disengagement at 1 year mediated the association between objective (95% bootstrap confidence interval = -0.282 to -0.042) and subjective (95% bootstrap confidence interval = 0.020 to 0.254) EFs at 6 months and depressive symptoms at 2 years.

Conclusions: This study highlights how problems with EF during survivorship are associated with avoidant coping and depressive symptoms. Thus, these findings identify potential cognitive and affective targets for depression intervention in this population.
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http://dx.doi.org/10.1097/PSY.0000000000000926DOI Listing
April 2021

Do all patients with cancer experience fatigue? A longitudinal study of fatigue trajectories in women with breast cancer.

Cancer 2021 Apr 19;127(8):1334-1344. Epub 2021 Feb 19.

Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California.

Background: Fatigue is a common and expected side effect of cancer treatment. However, the majority of studies to date have focused on average levels of fatigue, which may obscure important individual differences in the severity and course of fatigue over time. The current study was designed to identify distinct trajectories of fatigue from diagnosis into survivorship in a longitudinal study of women with early-stage breast cancer.

Methods: Women with stage 0 to stage IIIA breast cancer (270 women) were recruited before (neo)adjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy and completed assessments at baseline; posttreatment; and at 6 months, 12 months, and 18 months of follow-up. Growth mixture modeling was used to identify trajectories of fatigue, and differences among the trajectory groups with regard to demographic, medical, and psychosocial variables were examined.

Results: Five distinct trajectories of fatigue were identified: Stable Low (66%), with low levels of fatigue across assessments; Stable High (13%), with high fatigue across assessments; Decreasing (4%), with high fatigue at baseline that resolved over time; Increasing (9%), with low fatigue at baseline that increased over time; and Reactive (8%), with increased fatigue after treatment that resolved over time. Both psychological and treatment-related factors were found to be associated with fatigue trajectories, with psychological factors most strongly linked to high fatigue at the beginning of and over the course of treatment.

Conclusions: There is considerable variability in the experience of fatigue among women with early-stage breast cancer. Although the majority of women report relatively low fatigue, those with a history of depression and elevated psychological distress may be at risk of more severe and persistent fatigue.
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http://dx.doi.org/10.1002/cncr.33327DOI Listing
April 2021

Prediction of Breast Cancer Treatment-Induced Fatigue by Machine Learning Using Genome-Wide Association Data.

JNCI Cancer Spectr 2020 Oct 11;4(5):pkaa039. Epub 2020 May 11.

Gustave Roussy, INSERM Unit 981, Villejuif, France.

Background: We aimed at predicting fatigue after breast cancer treatment using machine learning on clinical covariates and germline genome-wide data.

Methods: We accessed germline genome-wide data of 2799 early-stage breast cancer patients from the Cancer Toxicity study (NCT01993498). The primary endpoint was defined as scoring zero at diagnosis and higher than quartile 3 at 1 year after primary treatment completion on European Organization for Research and Treatment of Cancer quality-of-life questionnaires for Overall Fatigue and on the multidimensional questionnaire for Physical, Emotional, and Cognitive fatigue. First, we tested univariate associations of each endpoint with clinical variables and genome-wide variants. Then, using preselected clinical (false discovery rate < 0.05) and genomic ( < .001) variables, a multivariable preconditioned random-forest regression model was built and validated on a hold-out subset to predict fatigue. Gene set enrichment analysis identified key biological correlates (MetaCore). All statistical tests were 2-sided.

Results: Statistically significant clinical associations were found only with Emotional and Cognitive Fatigue, including receipt of chemotherapy, anxiety, and pain. Some single nucleotide polymorphisms had some degree of association ( < .001) with the different fatigue endpoints, although there were no genome-wide statistically significant ( < 5.00 × 10) associations. Only for Cognitive Fatigue, the predictive ability of the genomic multivariable model was statistically significantly better than random (area under the curve = 0.59,  = .01) and marginally improved with clinical variables (area under the curve = 0.60,  = .005). Single nucleotide polymorphisms found to be associated ( < .001) with Cognitive Fatigue belonged to genes linked to inflammation (false discovery rate adjusted  = .03), cognitive disorders ( = 1.51 × 10), and synaptic transmission ( = 6.28 × 10).

Conclusions: Genomic analyses in this large cohort of breast cancer survivors suggest a possible genetic role for severe Cognitive Fatigue that warrants further exploration.
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http://dx.doi.org/10.1093/jncics/pkaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583150PMC
October 2020

Incorporating the Risk for Subsequent Primary Cancers Into the Care of Adult Cancer Survivors: Moving Beyond 5-Year Survival.

JAMA 2020 12;324(24):2493-2495

UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.

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http://dx.doi.org/10.1001/jama.2020.23410DOI Listing
December 2020

Anti-mullerian hormone as a serum biomarker for risk of chemotherapy-induced amenorrhea.

J Natl Cancer Inst 2020 Nov 7. Epub 2020 Nov 7.

Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, CA, USA AND NRG Oncology.

Anti-mullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and one year after initiation of adjuvant chemotherapy on NSABP/NRG Oncology B-47 in female participants aged 42 years and younger (with median age 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were <0.1ng/mL (the threshold for detectable levels, in the perimenopause/menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Post-chemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having post-chemotherapy menses increased with younger age, higher BMI, and higher pre-chemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs. docetaxel-cyclophosphamide). We conclude that higher pre-chemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea, and that AMH one year after chemotherapy initiation is not informative in this setting because it is likely to be very low.
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http://dx.doi.org/10.1093/jnci/djaa160DOI Listing
November 2020

Breast Cancer Risk-Reducing Medications.

JAMA 2020 07;324(3):310

UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California.

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http://dx.doi.org/10.1001/jama.2020.11784DOI Listing
July 2020

Assessing the Quality of Rectal Cancer Pathology Reports in National Surgical Adjuvant Breast and Bowel Project Protocol R-04/NRG Oncology.

Dis Colon Rectum 2020 08;63(8):1063-1070

Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.

Background: Accurate and comprehensive surgical pathology reports are integral to the quality of cancer care. Despite guidelines from the College of American Pathologists, variations in reporting quality continue to exist.

Objective: The aim of this study was to evaluate the quality of rectal cancer pathology reports and to identify areas of deficiency and potential sources of reporting variations.

Design: This is a retrospective analysis of prospectively obtained pathology reports.

Setting: This study is based at the hospitals participating in the National Surgical Adjuvant Breast and Bowel Project Protocol R-04 study.

Patients: Patients with rectal cancer undergoing surgical resection between July 2004 and August 2010 were included.

Main Outcome Measures: The primary outcomes measured were the adherence to the College of American Pathologists guidelines and the impact of synoptic reporting, academic status, rural/urban setting, and hospital bed size on reporting quality.

Results: We identified 1004 surgical pathology reports for rectal cancer surgery from 383 hospitals and 755 pathologists. The overall adherence rate to the College of American Pathologists guidelines was 73.3%. Notable reporting deficiencies were found in several key pathology characteristics, including tumor histologic grade (reporting rate 77.8%), radial margin (84.6%), distance from the closest margin (47.9%), treatment effect (47.1%), and lymphovascular (73.1%)/perineural invasions (35.4%). Synoptic reporting use and urban hospital settings were associated with better adherence rates, whereas academic status and hospital bed size had no impact. Reporting variations existed not only between institutions, but also within individual hospitals and pathologists. There was a trend for improved adherence over time (2005 = 65.7% vs 2010 = 82.3%, p < 0.001), which coincided with the increased adoption of synoptic reporting by pathologists (2005 vs 2010, 9.4% vs 25.3%, p < 0.001).

Limitations: Data were obtained from a restricted setting (ie, hospitals participating in a randomized clinical trial).

Conclusions: Wide variations in the quality of pathology reporting are observed for rectal cancer. The National Accreditation Program for Rectal Cancer mandates that programs meet strict quality standards for surgical pathology reporting. Further improvement is needed in this key aspect of oncology care for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/B238.ClinicalTrials.gov registration: NCT00058 EVALUACIÓN DE LA CALIDAD DE LOS INFORMES DE PATOLOGÍA QUIRÚRGICA EN CASOS DE CÁNCER DE RECTO DEL NSABP R-04/ ONCOLOGÍA DEL NRG: Un informe de patología quirúrgica preciso y completo es fundamental en la calidad de atención de pacientes con cáncer. A pesar de las normas establecidas por el Colegio Americano de Patología, la variabilidad en la calidad de los informes es evidente.Evaluar la calidad de los informes de patología en casos de cáncer de recto para así identificar las áreas con deficiencias y las posibles fuentes variables en los mencionados informes.Análisis retrospectivo de informes de patología quirúrgica obtenidos prospectivamente.Hospitales que participan del Protocolo del Estudio Nacional R-04 como Adyuvantes Quirúrgicos de Mama e Intestino.Todos aquellos pacientes con cáncer de recto sometidos a resección quirúrgica entre Julio 2004 y Agosto 2010.Cumplimiento de las normas del Colegio Americano de Patología, del impacto de los informes sinópticos, del estado académico, del entorno rural / urbano y el número de camas hospitalarias en en la calidad de los informes.Identificamos 1,004 informes de patología quirúrgica en casos de cirugía en cáncer de recto en 383 hospitales y 755 patólogos. La tasa general de adherencia a las directivas del Colegio Americano de Patología fue del 73.3%. Se encontraron deficiencias notables en los informes en varias características patológicas clave incluidos, el grado histológico del tumor (tasa de informe 77.8%), margenes radiales (84.6%), distancia del margen más cercano (47.9%), efecto del tratamiento (47.1%) invasión linfovascular (73.1 %) / invasion perineural (35.4%). El uso de informes sinópticos y los entornos hospitalarios urbanos se asociaron con mejores tasas de adherencia, mientras que el estado académico y el número de camas hospitalarias no tuvieron ningún impacto. Hubo variaciones en los informes no solo entre instituciones, sino también dentro de hospitales y patólogos individuales. Hubo una tendencia a una mejor adherencia a lo largo del tiempo (2005 = 65.7% v 2010 = 82.3%, p < 0.001), que coincidió con la mayor adopción de informes sinópticos por parte de los patólogos (2005 v 2010, 9.4% v 25.3%, p < 0.001)Datos obtenidos de un entorno restringido (es decir, hospitales que participan en un ensayo clínico aleatorizado).Se observaron grandes variaciones en la calidad de los informes de patología quirúrgica en casos de cáncer de recto. El Programa Nacional de Acreditación para Cáncer de Recto exige que los programas cumplan con estrictos estándares de calidad para los informes de patología quirúrgica. Se necesita una mejoría adicional en este aspecto clave de la atención oncológica para pacientes con cáncer de recto. Video Resumen en http://links.lww.com/DCR/B238.Registro de Clinical Trials.gov: NCT00058.
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http://dx.doi.org/10.1097/DCR.0000000000001578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787113PMC
August 2020

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants.

Genet Med 2020 10 15;22(10):1653-1666. Epub 2020 Jul 15.

Royal Devon & Exeter Hospital, Department of Clinical Genetics, Exeter, UK.

Purpose: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.

Methods: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.

Results: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10) carriers. The associations in the prospective cohort were similar.

Conclusion: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
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http://dx.doi.org/10.1038/s41436-020-0862-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521995PMC
October 2020

Engaging Latino Adolescent and Young Adult (AYA) Cancer Survivors in Their Care: Piloting a Photonovela Intervention.

J Cancer Educ 2020 Apr 24. Epub 2020 Apr 24.

Padres Contra El Cáncer (PADRES), Toluca Lake, CA, 91602, USA.

Latino adolescent and young adult (AYA) cancer survivors represent a growing population given the changing demographics in the USA. They experience significant healthcare disparities and barriers that warrant age-specific and culturally appropriate interventions to improve their clinical and psychosocial outcomes. This single-arm pilot study evaluated a novel intervention - a photonovela - on its ability to educate Latino AYA survivors and their family members and engage them in survivorship care. Ninety-seven participants (Latino AYA survivors and their family members) were recruited for this study. Three surveys assessing survivorship care confidence, cancer stigma, and survivorship care knowledge were administered to families before they received the photonovela, after the intervention, and at a booster phone call session. Mixed effects models were used to evaluate differences in scores at the three time points while accounting for repeated measures and family clustering. Results show that the photonovela was effective in improving survivorship care confidence and knowledge of Latino AYA survivors and their families. This pilot study indicates that the photonovela has potential to be a useful intervention for improving confidence and knowledge regarding the need to seek survivorship care for Latino AYA cancer survivors.
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http://dx.doi.org/10.1007/s13187-020-01724-2DOI Listing
April 2020

Childhood maltreatment and monocyte gene expression among women with breast cancer.

Brain Behav Immun 2020 08 2;88:396-402. Epub 2020 Apr 2.

UCLA Department of Psychiatry and Biobehavioral Sciences, United States; Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, United States; Jonsson Comprehensive Cancer Center, United States; UCLA Department of Medicine, United States.

Background: Childhood adversity is reliably associated with immune alterations in adulthood, including increases in inflammatory processes. However, relatively few studies have investigated these associations in clinical populations such as cancer patients who are at risk for negative immune-related health outcomes. The current study tested the hypothesis that childhood maltreatment would be associated with alterations in immune-related gene expression in monocytes from women with breast cancer.

Methods: Women (n = 86) were recruited after diagnosis with early-stage breast cancer but before onset of adjuvant therapy with radiation, chemotherapy, and/or endocrine therapy. Participants completed questionnaires to assess childhood maltreatment (Childhood Trauma Questionnaire; CTQ) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) and provided blood samples for immune assessment. CD14+ monocytes were isolated for RNA extraction and gene expression analyses.

Results: Based on responses to the CTQ, 28% of participants were classified as experiencing physical and/or emotional abuse or neglect and 7% as experiencing sexual abuse. Genome-wide transcriptional profiling of isolated monocytes identified 202 gene transcripts that differed in average expression level by > 25% over the range of maltreatment exposure. Bioinformatics analyses of those gene transcripts identified a significantly greater prevalence of NF-κB-binding motifs within the promoters of up-regulated vs. down-regulated genes (p = .028) in women exposed to childhood maltreatment, indicating greater inflammatory signaling. Parallel analyses of Type I interferon signaling also indicated greater prevalence of Interferon Response Factor (IRF)-related binding sites in women with a childhood maltreatment history (p = .020). Results remained significant in analyses controlling for current depression; however, NF-κB and IRF-related gene expression was higher in women with both maltreatment exposure and current depression.

Conclusions: In women recently diagnosed with early-stage breast cancer, childhood maltreatment was associated with increases in the classical NF-kB-related pro-inflammatory signaling pathway and with increases in the Type I interferon system. These results suggest a broad pattern of chronic immunologic activation in breast cancer patients with a history of childhood maltreatment, particularly those who are currently experiencing clinically significant depressive symptoms. These findings have implications for the long-term health and well-being of maltreatment exposed breast cancer patients.
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http://dx.doi.org/10.1016/j.bbi.2020.04.001DOI Listing
August 2020

Cognitive Impairment in Patients With Breast Cancer: Understanding the Impact of Chemotherapy and Endocrine Therapy.

J Clin Oncol 2020 06 6;38(17):1871-1874. Epub 2020 Mar 6.

University of California Los Angeles Jonsson Comprehensive Cancer Center, and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.

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http://dx.doi.org/10.1200/JCO.20.00336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280046PMC
June 2020

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status.

Genet Epidemiol 2020 07 1;44(5):442-468. Epub 2020 Mar 1.

Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
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http://dx.doi.org/10.1002/gepi.22288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987299PMC
July 2020

Evaluating Treatment Tolerability in Cancer Clinical Trials Using the Toxicity Index.

J Natl Cancer Inst 2020 12;112(12):1266-1274

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Background: The National Cancer Institute Moonshot research initiative calls for improvements in the analysis and reporting of treatment toxicity to advise key stakeholders on treatment tolerability and inform regulatory and clinical decision making. This study illustrates alternative approaches to toxicity evaluation using the National Surgical Adjuvant Breast and Bowel Project R-04 clinical trial as an example.

Methods: National Surgical Adjuvant Breast and Bowel Project R-04 was a neoadjuvant chemoradiation trial in stage II-III rectal cancer patients. A 2 x 2 factorial design was used to evaluate whether the addition of oxaliplatin (Oxa) to 5-fluorouracil (5FU) or capecitabine (Cape) with radiation therapy improved local-regional tumor control. The toxicity index (TI), which accounts for the frequency and severity of toxicities, was compared across treatments using multivariable probabilistic index models, where Pr A < B indicates the probability that higher values of TI were observed for A when compared with B. Baseline age, sex, performance status, body mass index, surgery type, and stage were evaluated as independent risk factors.

Results: A total of 4560 toxicities from 1558 patients were analyzed. Results from adjusted probabilistic index models indicate that oxaliplatin-containing regimens had statistically significant (P < .001) probability (Pr) for higher TI compared with regimens without oxaliplatin (Pr 5FU < 5FU + Oxa = 0.619, 95% confidence interval [CI] = 0.560 to 0.674; Pr 5FU < Cape + Oxa = 0.627, 95% CI = 0.568 to 0.682; Pr Cape < 5FU + Oxa = 0.587, 95% 0.527 to 0.644; and Pr Cape < Cape + Oxa = 0.596, 95% 0.536 to 0.653). When compared with other existing toxicity analysis methods, TI provided greater power to detect differences between treatments.

Conclusions: This article uses standard data collected in a cancer clinical trial to introduce descriptive and analytic methods that account for the additional burden of multiple toxicities. These methods may provide a more accurate description of a patient's treatment experience that could lead to individualized dosing for better toxicity control. Future research will evaluate the generalizability of these findings in trials with similar drugs.
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http://dx.doi.org/10.1093/jnci/djaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735773PMC
December 2020

Identifying Cancer-Related Cognitive Impairment Using the FACT-Cog Perceived Cognitive Impairment.

JNCI Cancer Spectr 2020 Feb 29;4(1):pkz099. Epub 2019 Nov 29.

See the Notes section for the full list of authors' affiliations.

Cancer-related cognitive impairment (CRCI) is a concerning problem for many cancer survivors. Evaluating patients for CRCI has been a challenge, in part because of a lack of standardized practices. Self-report instruments are often used to assess CRCI, but there are no validated cutpoints. We present the results of receiver operating characteristic curve analysis identifying cutpoints of the Functional Assessment of Cancer Therapy-Cognition perceived cognitive impairment (PCI) in female breast cancer survivors for identifying CRCI cases. We defined presence of CRCI based on elevated complaints on the Patient's Assessment of Own Functioning Inventory compared with healthy control scores. Our results indicate that scores less than 54 in PCI scores using 18 items and scores less than 60 in PCI scores using 20 items exhibited good ability to discriminate CRCI cases from noncases (area under the receiver operating characteristic curve was 0.84 [95% CI = 0.73 to 0.94]). These preliminary results represent an important contribution toward standardizing practices across CRCI studies.
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http://dx.doi.org/10.1093/jncics/pkz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015054PMC
February 2020

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Nat Genet 2020 01 7;52(1):56-73. Epub 2020 Jan 7.

Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
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http://dx.doi.org/10.1038/s41588-019-0537-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974400PMC
January 2020

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.

Lancet 2019 12 5;394(10215):2155-2164. Epub 2019 Dec 5.

NRG Oncology, Pittsburgh, PA, USA; University of Pittsburgh, Pittsburgh, PA, USA; Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA.

Background: Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation.

Methods: We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181.

Findings: Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group.

Interpretation: APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women.

Funding: National Cancer Institute, US Department of Health and Human Services.
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http://dx.doi.org/10.1016/S0140-6736(19)32514-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199428PMC
December 2019

Follow-up Care for Breast Cancer Survivors.

J Natl Cancer Inst 2020 01;112(1):111-113

Division of Health Care Policy and Research (NDS), Mayo Clinic, Rochester, MN.

Breast cancer survivorship guidelines recommend at least annual follow-up visits, yet the degree to which this occurs in clinical practice is uncertain. Claims data from a US commercial insurance database (OptumLabs) were used to identify women treated with curative intent surgery for newly diagnosed breast cancer between 2006 and 2014. In 25 035 women, median follow-up was 3 years. In the second year after surgery, 9.6% of the patients did not visit a primary care provider, an oncologist, or a surgeon (guideline-nonadherent). The guideline-nonadherent proportion increased from 7.8% in women diagnosed in 2006 to 12.2% in those diagnosed in 2014 (two-sided Wald P < .001). During years 2-6, guideline-nonadherence was also associated with older age, nonwhite race, no radiation, no chemotherapy, no endocrine therapy, and increasing time after surgery. There is a substantial and increasing rate of inadequate follow-up among breast cancer survivors. This has the potential to impair outcomes.
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http://dx.doi.org/10.1093/jnci/djz203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849972PMC
January 2020

Evidence map of ductal carcinoma in situ management options.

Menopause 2019 11;26(11):1250-1258

RAND Corporation, Southern California Evidence-Based Practice Center, Santa Monica, CA.

Objective: Ductal carcinoma in situ (DCIS) has the potential to progress to invasive carcinoma. The optimal management of DCIS and methods for individualizing treatment of DCIS are still being determined. This evidence map depicts the robustness and topical span of research on DCIS management choice on patient-centered and clinical outcomes.

Methods: We searched PubMed, EMBASE, PsycINFO, PubMed Health, PROSPERO, and clinical practice guideline sites to identify systematic reviews of DCIS management options and consulted with topic experts. A bubble plot visualizes the literature volume and research content for patient-centered outcomes. An online decision tree facilitates discussions with patients and guides through the available evidence.

Results: In total, 40 systematic reviews met inclusion criteria. The research syntheses addressed DCIS management options, including the role of magnetic resonance imaging, axillary surgery/sentinel lymph node biopsy, and excisional biopsy. The map shows existing evidence for mutually exclusive treatment options including active surveillance, breast-conserving surgery, nipple sparing mastectomy, and simple mastectomy. Research findings for intraoperative radiation, adjuvant radiation therapy, adjuvant hormone therapy, hypofractionation radiotherapy, accelerated partial breast irradiation, radiation therapy plus boost, and combined radiation and hormone therapy, as well as for breast reconstruction after mastectomy and surveillance mammography postsurgery are also displayed. The evidence map highlights a scarcity of robust evidence on patient-centered outcomes.

Conclusions: The evidence map provides an overview of DCIS research showing the range of management options and remaining decisional dilemmas that follow a diagnosis of DCIS. It maps the evidence in accessible tools to guide practice and future research. : Video Summary:http://links.lww.com/MENO/A448.
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http://dx.doi.org/10.1097/GME.0000000000001397DOI Listing
November 2019

The Hazards of Assessing the Carcinogenicity of Agents.

Authors:
Patricia A Ganz

J Natl Cancer Inst 2020 01;112(1):1-2

Health Policy & Management and Medicine, UCLA Fielding School of Public Health and David Geffen School of Medicine, UCLA.

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http://dx.doi.org/10.1093/jnci/djz170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968682PMC
January 2020

Potential Mechanisms of Age Acceleration Caused by Estrogen Deprivation: Do Endocrine Therapies Carry the Same Risks?

JNCI Cancer Spectr 2018 Jul 10;2(3):pky035. Epub 2018 Sep 10.

Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.

Longer duration of endocrine therapy decreases breast cancer recurrence and mortality, but these benefits need to be weighed against potential risks to overall health. Notable side effects of endocrine therapy include cataracts, uterine cancer, thromboembolic events, osteoporosis and fracture risk, chronic musculoskeletal complaints, as well as vaginal dryness and discharge, and vasomotor symptoms. Estrogen deprivation in healthy women younger than 50 years undergoing bilateral oophorectomy has been shown to accelerate the development of diseases related to aging, including coronary artery disease, cardiac arrhythmias, stroke, dementia, and osteoporosis, raising concern that even less dramatic modulation of estrogen homeostasis may adversely affect health outcomes. Diminished available estrogen at the cellular and molecular level may facilitate mechanisms that underlie the aging process, often termed the hallmarks of aging. In this review, we describe estrogen's role in normal physiology across tissues, review the effects of estrogen deprivation on health outcomes in the setting of both surgical and natural menopause, and examine the hallmarks of aging with attention to the effects of estrogen and estrogen blockade on each molecular mechanism underlying the aging process.
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http://dx.doi.org/10.1093/jncics/pky035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649786PMC
July 2018

The use of mobile technology and peer navigation to promote adolescent and young adult (AYA) cancer survivorship care: results of a randomized controlled trial.

J Cancer Surviv 2019 Aug 26;13(4):580-592. Epub 2019 Jul 26.

Department of Computer Science, Cornell University, New York, NY, USA.

Purpose: Adolescent and young adult (AYA) cancer survivors experience unique barriers that compromise receipt of survivorship care; therefore, development of innovative educational interventions to improve rates of AYA survivorship care is needed. The efficacy of text-messaging and peer navigation interventions was compared to standard-of-care survivorship educational materials to increase AYAs' (1) late effects knowledge and (2) knowledge, attitudes, and self-efficacy towards seeking survivor-focused care.

Methods: This was a three-armed, prospective, randomized controlled trial with one control group and two intervention groups. The control group received current standard-of-care educational materials. One intervention group participated in a text-messaging program, and the second participated in a peer navigator program. Participants completed pre- and post-intervention questionnaires. Study outcome variables were quantified using Fisher exact tests, two-sample t tests, exact McNemar tests, conditional logistic regression models, and analysis of covariance.

Results: Seventy-one survivors completed the study (control n = 24; text-messaging n = 23; peer navigation n = 24). Late effects knowledge was high at baseline for all groups. The text-messaging group had increased survivorship care knowledge compared to the control group (p < 0.05); the peer navigation group had increased survivorship care self-efficacy compared to the control group; p < 0.05. Both intervention groups showed increased attitudes towards seeking survivor-focused care compared to the control group (text-messaging p < 0.05; peer navigation p < 0.05).

Conclusions: Each intervention demonstrated significant benefits compared to the control group.

Implications For Cancer Survivors: Given the preliminary effectiveness of both interventions, each can potentially be used in the future by AYA cancer survivors to educate and empower them to obtain needed survivorship care.
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http://dx.doi.org/10.1007/s11764-019-00777-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045289PMC
August 2019

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Br J Cancer 2019 07 19;121(2):180-192. Epub 2019 Jun 19.

Department of Gynaecological Oncology, Chris O'Brien Lifehouse and The University of Sydney, Camperdown, NSW, Australia.

Background: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.

Results: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P < 0.05).

Conclusion: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.
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http://dx.doi.org/10.1038/s41416-019-0492-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738050PMC
July 2019

The inflammation complication: New evidence in cancer-related cognitive impairment.

Brain Behav Immun 2019 10 7;81:6-7. Epub 2019 Jun 7.

UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA; UCLA David Geffen School of Medicine, Los Angeles, CA, USA; UCLA Fielding School of Public Health, Los Angeles, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2019.06.013DOI Listing
October 2019