Karen Gelmon

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada

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Publications (114)1054.27 Total impact

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    ABSTRACT: The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue.
    Journal of Medical Screening 09/2014; · 2.35 Impact Factor
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    ABSTRACT: Background:The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses.Methods:Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables.Results:Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions.Conclusions:Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.British Journal of Cancer advance online publication, 21 August 2014; doi:10.1038/bjc.2014.466 www.bjcancer.com.
    British journal of cancer. 08/2014;
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    ABSTRACT: Background Exercise is beneficial for breast cancer patients during chemotherapy but adherence to different types and doses of exercise is a challenge. The purpose of this study was to examine predictors of adherence to different types and doses of exercise during breast cancer chemotherapy in a multicenter randomized controlled trial.Methods Breast cancer patients in Edmonton, Vancouver, and Ottawa, Canada receiving chemotherapy (N¿=¿301) were randomized to a standard dose of 25¿30 minutes of aerobic exercise (STAN), a higher dose of 50¿60 minutes of aerobic exercise (HIGH), or a higher dose of 50¿60 minutes of combined aerobic and resistance exercise (COMB). Predictors included demographic, medical, fitness, and quality of life variables. Exercise adherence was measured as the percentage of supervised exercise sessions completed.ResultsOverall adherence to the supervised exercise sessions was 73% (SD¿=¿24%). In a multivariate regression model, six independent predictors explained 26.4% (p¿<¿0.001) of the variance in exercise adherence. Higher exercise adherence was achieved by breast cancer patients in Vancouver (p¿<¿0.001), with fewer endocrine symptoms (p¿=¿0.009), randomized to STAN (p¿=¿0.009), with fewer exercise limitations (p¿=¿0.009), receiving shorter chemotherapy protocols (p¿=¿0.015), and with higher VO2peak (p¿=¿0.017). Disease stage (p for interaction¿=¿0.015) and body mass index (p for interaction¿=¿0.030) interacted with group assignment to predict adherence. For disease stage, patients with stage I/IIa disease adhered equally well to all three exercise interventions whereas patients with stage IIb/III disease adhered better to the STAN intervention than the two higher dose exercise interventions. For body mass index, healthy weight patients adhered equally well to all three exercise interventions whereas overweight patients adhered best to STAN and worst to COMB; and obese patients adhered best to STAN and worst to HIGH.Conclusions Determinants of exercise adherence in breast cancer patients receiving chemotherapy are multidisciplinary and may vary by the exercise prescription.
    International Journal of Behavioral Nutrition and Physical Activity 07/2014; 11(1):85. · 3.58 Impact Factor
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    ABSTRACT: Observational studies suggest that physical activity after a breast cancer diagnosis is associated with improved cancer outcomes; however, no randomized data are available. Here, we report an exploratory follow-up of cancer outcomes from the Supervised Trial of Aerobic versus Resistance Training (START). The START Trial was a Canadian multicenter trial that randomized 242 breast cancer patients between 2003-2005 to usual care (n = 82), supervised aerobic (n = 78) or resistance (n = 82) exercise during chemotherapy. The primary endpoint for this exploratory analysis was disease-free survival (DFS). Secondary endpoints were overall survival (OS), distant disease-free survival (DDFS), and recurrence-free interval (RFI). The two exercise arms were combined for analysis (n = 160) and selected subgroups were explored. After a median follow-up of 89 months, there were 25/160 (15.6%) DFS events in the exercise groups and 18/82 (22.0%) in the control group. Eight-year DFS was 82.7% for the exercise groups compared with 75.6% for the control group (Hazard ratio [HR]= 0.68, 95% CI = 0.37-1.24; log-rank p = 0.21). Slightly stronger effects were observed for OS (HR = 0.60, 95% CI = 0.27 to 1.33; log-rank p = 0.21), DDFS (HR = 0.62, 95% CI = 0.32 to 1.19; log-rank p = 0.15), and RFI (HR = 0.58, 95% CI = 0.30 to 1.11; Gray's p = 0.095). Subgroup analyses suggested potentially stronger exercise effects on DFS for women who were overweight/obese (HR = 0.59, 95% CI = 0.27-1.27), had stage II/III cancer (HR = 0.61, 95% CI = 0.31-1.20), ER positive tumors (HR = 0.58, 95% CI = 0.26-1.29), HER2 positive tumors (HR = 0.21, 95% CI = 0.04-1.02), received taxane-based chemotherapies (HR = 0.46, 95% CI = 0.19-1.15), and ≥ 85% of their planned chemotherapy (HR = 0.50, 95% CI = 0.25-1.01). This exploratory follow-up of the START Trial provides the first randomized data to suggest that adding exercise to standard chemotherapy may improve breast cancer outcomes. A definitive phase III trial is warranted.
    Medicine and science in sports and exercise 03/2014; · 4.48 Impact Factor
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    ABSTRACT: Background: Exercise may improve psychosocial distress in cancer patients; however, few studies have examined the effects of different types or doses of exercise, or whether exercise effects are related to baseline depression levels. Methods: In a multicenter trial in Canada, we randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of either a standard dose of 25-30 minutes of aerobic exercise (STAN; n=96), a higher dose of 50-60 minutes of aerobic exercise (HIGH; n=101), or a combined dose of 50-60 minutes of aerobic and resistance exercise (COMB; n=104). The primary endpoint was depression assessed by the Center for Epidemiological Studies-Depression (CES-D) scale at baseline, twice during chemotherapy, and postchemotherapy. Secondary endpoints were anxiety, perceived stress, and self-esteem. Results: Repeated measures analyses of variance indicated that neither HIGH (mean difference= -0.9; 95% CI= +0.0 to -1.8; p=0.061) nor COMB (mean difference= -0.4; 95% CI= +0.5 to -1.3; p=0.36) were superior to STAN for managing depressive symptoms. In a planned subgroup analysis, there was a significant interaction with baseline depression levels (p for interaction=0.027) indicating that COMB and HIGH were effective for managing depressive symptoms in patients with clinical levels of depressive symptoms at baseline. Conclusions: Compared to a standard volume of aerobic exercise, higher volumes of exercise did not help manage depressive symptoms in unselected breast cancer patients receiving chemotherapy, but they were effective in patients with clinical levels of depressive symptoms at baseline. Impact: A phase III exercise trial targeting depressed breast cancer patients is warranted.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2014; · 4.56 Impact Factor
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    ABSTRACT: To examine the effects of different doses and types of exercise on sleep quality in breast cancer patients receiving chemotherapy. A multicenter trial in Canada randomized 301 breast cancer patients between 2008 and 2011 to thrice weekly, supervised exercise during chemotherapy consisting of either a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101), or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104). The secondary sleep outcomes in the trial were assessed by the Pittsburgh Sleep Quality Index (PSQI) at baseline, twice during chemotherapy, and postchemotherapy. We analyzed the global PSQI and the component scores. Repeated measures analyses of variance indicated that the HIGH group was statistically superior to the STAN group for global sleep quality (mean group difference = -0.90; 95 % CI -0.05 to -1.76; p = 0.039) as well as subjective sleep quality (p = 0.028) and sleep latency (p = 0.049). The COMB group was borderline statistically superior to the STAN group for global sleep quality (mean group difference = -0.76; 95 % CI +0.11 to -1.62; p = 0.085) as well as sleep duration (p = 0.051); and statistically superior for sleep efficiency (p = 0.040), and percentage of poor sleepers (p = 0.045). Compared to a standard volume of aerobic exercise, higher volumes of both aerobic and combined exercise improved some aspects of sleep quality during breast cancer chemotherapy. Exercise may be an attractive option to manage sleep dysfunction in cancer patients during chemotherapy.
    Breast Cancer Research and Treatment 02/2014; · 4.47 Impact Factor
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    ABSTRACT: Purpose Optimal local management for young women with early-stage breast cancer remains controversial. This study examined 15-year outcomes among women younger than 40 years treated with breast-conserving surgery plus whole-breast radiation therapy (BCT) compared with those treated with modified radical mastectomy (MRM). Methods and Materials Women aged 20 to 39 years with early-stage breast cancer diagnosed between 1989 and 2003 were identified in a population-based database. Primary outcomes of breast cancer–specific survival (BCSS), overall survival (OS) and secondary outcomes of local relapse–free survival (LRFS), locoregional relapse–free survival (LRRFS), and distant relapse–free survival (DRFS) were calculated using Kaplan-Meier methods and compared between BCT and MRM cohorts using log-rank tests. A planned subgroup analysis was performed on patients considered “ideal” for BCT (ie, T1N0, negative margins and no extensive ductal carcinoma in situ) and in whom local therapy may have the largest impact on survival because of low systemic risk. Results 965 patients were identified; 616 had BCT and 349 had MRM. The median follow-up time was 14.4 years (range, 8.4-23.3 years). Overall, 15-year rates of BCSS (76.0% vs 74.1%, P=.62), OS (74.2% vs 73.0%, P=.75), LRFS (85.4% vs 86.5%, P=.95), LRRFS (82.2% vs 81.6%, P=.61), and DRFS (74.4% vs 71.6%, P=.40) were similar between the BCT and MRM cohorts. In the “ideal” for BCT subgroup, there were 219 BCT and 67 MRM patients with a median follow-up time of 15.5 years. The 15-year BCSS (86.1% vs 82.9%, P=.57), OS (82.6% vs 82.9%, P=.89), LRFS (86.2% vs 84.2%, P=.50), LRRFS (83.1% vs 78.3%, P=.24), and DRFS (84.8% vs 79.1%, P=.17) were similar in the BCT and MRM cohorts. Conclusions This population-based analysis with long-term follow-up confirmed that women younger than 40 years treated with BCT had similar 15-year outcomes compared with MRM. Young age alone is not a contraindication to BCT.
    International journal of radiation oncology, biology, physics 01/2014; · 4.59 Impact Factor
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    ABSTRACT: To help facilitate economic evaluations of oncology treatments, we mapped responses on cancer-specific instrument to generic preference-based measures. Cancer patients (n = 367) completed one cancer-specific instrument, the FACT-G, and two preference-based measures, the EQ-5D and SF-6D. Responses were randomly divided to form development (n = 184) and cross-validation (n = 183) samples. Relationships between the instruments were estimated using ordinary least squares (OLS), generalized linear models (GLM), and censored least absolute deviations (CLAD) regression approaches. The performance of each model was assessed in terms of how well the responses to the cancer-specific instrument predicted EQ-5D and SF-6D utilities using mean absolute error (MAE) and root mean squared error (RMSE). Physical, functional, and emotional well-being domain scores of the FACT-G best explained the EQ-5D and SF-6D. In terms of accuracy of prediction as measured in RMSE, the CLAD model performed best for the EQ-5D (RMSE = 0.095) whereas the GLM model performed best for the SF-6D (RMSE = 0.061). The GLM predicted SF-6D scores matched the observed values more closely than the CLAD and OLS. Our results demonstrate that the estimation of both EQ-5D and SF-6D utility indices using the FACT-G responses can be achieved. The CLAD model for the EQ-5D and the GLM model for the SF-6D are recommended. Thus, it is possible to estimate quality-adjusted life years for economic evaluation from studies where only cancer-specific instrument have been administered.
    Health and Quality of Life Outcomes 12/2013; 11(1):203. · 2.27 Impact Factor
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    ABSTRACT: Exercise improves physical functioning and symptom management during breast cancer chemotherapy, but the effects of different doses and types of exercise are unknown. A multicenter trial in Canada randomized 301 breast cancer patients to thrice-weekly supervised exercise during chemotherapy consisting of either a standard dose of 25 to 30 minutes of aerobic exercise (STAN; n = 96), a higher dose of 50 to 60 minutes of aerobic exercise (HIGH; n = 101), or a combined dose of 50 to 60 minutes of aerobic and resistance exercise (COMB; n = 104). The primary endpoint was physical functioning assessed by the Medical Outcomes Survey-Short Form (SF)-36. Secondary endpoints were other physical functioning scales, symptoms, fitness, and chemotherapy completion. All statistical tests were linear mixed model analyses, and the P values were two-sided. Follow-up assessment of patient-reported outcomes was 99.0%. Adjusted linear mixed-model analyses showed that neither HIGH (+0.8; 95% confidence interval [CI] = -0.8 to 2.4; P = .30) nor COMB (+0.5; 95% CI = -1.1 to 2.1; P = .52] were superior to STAN for the primary outcome. In secondary analyses not adjusted for multiple comparisons, HIGH was superior to STAN for the SF-36 physical component summary (P = .04), SF-36 bodily pain (P = .02), and endocrine symptoms (P = .02). COMB was superior to STAN for endocrine symptoms (P = .009) and superior to STAN (P < .001) and HIGH (P < .001) for muscular strength. HIGH was superior to COMB for the SF-36 bodily pain (P = .04) and aerobic fitness (P = .03). No differences emerged for body composition or chemotherapy completion. A higher volume of aerobic or combined exercise is achievable and safe during breast cancer chemotherapy and may manage declines in physical functioning and worsening symptoms better than standard volumes.
    CancerSpectrum Knowledge Environment 10/2013; · 14.07 Impact Factor
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    ABSTRACT: PURPOSEIn patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODS We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety.ResultsIn the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.
    Journal of Clinical Oncology 01/2013; · 18.04 Impact Factor
  • Rachel Cossetti, Karen Gelmon
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    ABSTRACT: The clinical course of HER2 positive (HER2+) breast cancer has changed since the introduction of trastuzumab, the first approved HER2 targeted agent. However, a significant number of patients relapse because of either de novo or acquired resistance to trastuzumab, imposing a need for other targeted agents. Lapatinib, the first targeted agent to demonstrate efficacy after trastuzumab progression, is licensed in combination with chemotherapy or with trastuzumab and has shown efficacy post-trastuzumab progression. Newer, recently approved agents include pertuzumab, an antibody preventing dimerization of HER2 and HER3, and T-DM1, an antibody-drug conjugate capable of delivering a highly cytotoxic agent into the cancer cells. Both agents have modest systemic toxicity. The dual combination of pertuzumab and trastuzumab given in combination with docetaxel is the current standard first-line treatment for HER2+ MBC. T-DM1 is now approved for second-line treatment. Specific clinical scenarios, including brain metastases, still lack good therapeutic options. Newer targeted agents are being tested with an exciting future for the treatment of HER2+ MBC although there are challenges to develop them in today’s environment. Clinicians now have a number of options for treatment of metastatic HER2 advanced breast cancer although access to some drugs may be limited globally, often because of economic realities.
    Current Breast Cancer Reports 01/2013; 5(4).
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    ABSTRACT: PURPOSECurrent immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. PATIENTS AND METHODS Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance.ResultsClinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. CONCLUSION Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%.
    Journal of Clinical Oncology 12/2012; · 18.04 Impact Factor
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    ABSTRACT: Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described. Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected. Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor-positive, node-negative breast cancer. Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.
    Journal of Clinical Oncology 05/2012; 30(18):2227-31. · 18.04 Impact Factor
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    ABSTRACT: Triple-negative breast cancer (TNBC) is a distinct subset of breast cancer (BC) defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. It is highly heterogeneous and displays overlapping characteristics with both basal-like and BC susceptibility gene 1 and 2 mutant BCs. This review evaluates the activity of emerging targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with targeted and platinum-based therapies. Our review identified TNBC studies of agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. Combining targeted agents with chemotherapy in TNBC produced only modest gains in progression-free survival, and had little impact on survival. Six TNBC subgroups have been identified and found to differentially respond to specific targeted agents. The use of biological preselection to guide therapy will improve therapeutic indices in target-bearing populations. Ongoing clinical trials of targeted agents in unselected TNBC populations have yet to produce substantial improvements in outcomes, and advancements will depend on their development in target-selected populations.
    Annals of Oncology 04/2012; 23(9):2223-34. · 7.38 Impact Factor
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    ABSTRACT: Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.
    Nature 04/2012; 486(7403):395-9. · 38.60 Impact Factor
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    ABSTRACT: Physical inactivity and being overweight or obese are lifestyle factors that put breast cancer survivors at a higher risk for a cancer recurrence and/or development of other chronic diseases. Despite this, there is limited research that has identified effective lifestyle interventions aimed specifically at weight loss in breast cancer survivors. This pilot study is a single-arm experimental pre-post test design, conducted from November 2009 to July 2010, that tested the efficacy of a 24-week group-based lifestyle intervention modeled on the Diabetes Prevention Program in early stage breast cancer survivors (N=14). The intervention included 16 diet sessions led by a registered dietitian and 150 min/wk of moderate-to-vigorous exercise. Study outcome measures were completed at baseline, 24, and 36 weeks (nonintervention follow-up). The primary outcome was change in body weight, and secondary outcomes were change in body composition, aerobic fitness, dietary intake, and blood biomarkers. Overall, participants were postmenopausal women aged 54.6±8.3 years with obesity (body mass index 30.1±3.6), and had completed adjuvant cancer treatment 2 years prior. Results showed an average weight loss of 3.8±5.0 kg and a decrease in body mass index, percent body fat, and waist and hip circumferences at 24 weeks and an additional mean weight loss of 0.8±1.2 kg at 36 weeks. In exploratory analysis, participants who lost >7% body weight were older and attended a greater percentage of diet and supervised exercise sessions. There were no significant changes in any of the blood biomarkers at 24 and 36 weeks; however, the results provide a measure of expected effect size for future research studies. This pilot study demonstrated the efficacy of a lifestyle intervention based on the Diabetes Prevention Program in early stage breast cancer survivors and represents an innovative clinical intervention for dietetics practitioners to address the unmet need for programs.
    Journal of the American Academy of Nutrition and Dietetics 04/2012; 112(4):559-67. · 3.80 Impact Factor
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    ABSTRACT: The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.
    Breast (Edinburgh, Scotland) 03/2012; 21(3):242-52. · 2.09 Impact Factor
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    ABSTRACT: Hormone receptor-positive advanced breast cancer is an increasing health burden. Although endocrine therapies are recognised as the most beneficial treatments for patients with hormone receptor-positive advanced breast cancer, the optimal sequence of these agents is currently undetermined. We reviewed the available data on randomised controlled trials (RCTs) of endocrine therapies in this treatment setting with particular focus on RCTs reported over the last 15 years that were designed based on power calculations on primary end points. In this paper, data are reviewed in postmenopausal patients for the use of tamoxifen, aromatase inhibitors and fulvestrant. We also consider the available data on endocrine crossover studies and endocrine therapy in combination with chemotherapy or growth factor therapies. Treatment options for premenopausal patients and those with estrogen receptor-/human epidermal growth factor receptor 2-positive tumours are also evaluated. We present the level of evidence available for each endocrine agent based on its efficacy in advanced breast cancer and a diagram of possible treatment pathways.
    Annals of Oncology 02/2012; 23(6):1378-86. · 7.38 Impact Factor
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    ABSTRACT: To evaluate the validity of cancer-specific and generic preference-based instruments to discriminate across different measures of cancer severities. Patients with breast (n = 66), colorectal (n = 57), and lung (n = 61) cancer completed the EORTC QLQ-C30 and the FACT-G, as well as three generic instruments: the EQ-5D, the SF-6D, and the HUI2/3. Disease severity was quantified using cancer stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score, and self-reported health status. Comparative analyses confirmed the multi-dimensional conceptualization of the instruments in terms of construct and convergent validity. In general, the instruments were able to discriminate across severity measures. The instruments demonstrated moderate to strong correlation with each other (r = 0.37-0.73). Not all of the measures could discriminate between different groups of disease severity: the EQ-5D and SF-6D were less discriminative than the HUI2/3 and the cancer-specific instruments. The cancer-specific and generic preference-based instruments demonstrated to be valid in discriminating across levels of ECOG-PS scores and self-reported health states. However, the usefulness of the generic instruments may be limited if they are not able to detect small changes in health status within cancer patients. This raises concerns regarding the appropriateness of these instruments when comparing different cancer treatments within an economic evaluation framework.
    Health and Quality of Life Outcomes 11/2011; 9:106. · 2.27 Impact Factor
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    ABSTRACT: The HER2 oncogene is overexpressed or amplified in 20% of breast cancers. HER2-positive cancer historically portends a poor prognosis, but the HER2-targeted therapy trastuzumab mitigates this otherwise ominous distinction. Nevertheless, some patients suffer disease recurrence despite trastuzumab, and metastatic disease remains largely incurable due to innate and acquired resistance. Thus, understanding trastuzumab resistance remains an unmet medical need. Through RNA interference screening, we discovered that knockdown of the serine/threonine phosphatase PPM1H confers trastuzumab resistance via reduction in protein levels of the tumor suppressor p27. PPM1H dephosphorylates p27 at threonine 187, thus removing a signal for proteasomal degradation. We further determined that patients whose tumors express low levels of PPM1H trend towards worse clinical outcome on trastuzumab. Identifying PPM1H as a novel p27 phosphatase reveals new insight into how cancer cells destabilize a well-recognized tumor suppressor. Furthermore, low PPM1H expression may identify a subset of HER2-positive tumors that are harder to treat.
    Cancer Discovery 09/2011; 1(4):326-37. · 10.14 Impact Factor

Publication Stats

4k Citations
1,054.27 Total Impact Points

Institutions

  • 1999–2013
    • University of British Columbia - Vancouver
      • • Department of Pathology and Laboratory Medicine
      • • Division of Medical Oncology
      Vancouver, British Columbia, Canada
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2004–2011
    • Vancouver Prostate Centre
      Vancouver, British Columbia, Canada
    • BC Cancer Research Centre
      • Canadian Centre for Applied Research in Cancer Control (ARCC)
      Vancouver, British Columbia, Canada
  • 2010
    • OICC - Ottawa Integrative Cancer Centre
      Ottawa, Ontario, Canada
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 2009
    • Government of British Columbia, Canada
      Vancouver, British Columbia, Canada
  • 2005–2009
    • BC Cancer Agency
      • Radiation Therapy Program
      Vancouver, British Columbia, Canada
  • 2007–2008
    • University of Alberta
      • Faculty of Physical Education and Recreation
      Edmonton, Alberta, Canada
  • 2006
    • Health Sciences North/Horizon Santé-Nord
      Greater Sudbury, Ontario, Canada
  • 1994–2004
    • Regional Integration Cancer Center
      Мендоса, Mendoza, Argentina
  • 1997
    • University of Victoria
      • Department of Biology
      Victoria, British Columbia, Canada
  • 1993
    • Dalhousie University
      Halifax, Nova Scotia, Canada