Quality and readability of online information and materials on post-surgery breast seroma.

Aims/Background Seroma formation is the most common complication following breast surgery. However, there is little evidence on the readability of online patient education materials on this issue. This study aimed to assess the accessibility and readability of the relevant online information. Methods This systematic review of the literature identified 37 relevant websites for further analysis. The readability of each online article was assessed through using a range of readability formulae. Results The average Flesch-Reading Ease score for all patient education materials was 53.9 (± 21.9) and the average Flesch-Kincaid reading grade level was 7.32 (± 3.1), suggesting they were 'fairly difficult' to read and is higher than the recommended reading level. Conclusion Online patient education materials regarding post-surgery breast seroma are at a higher-than-recommended reading grade level for the public. Improvement would allow all patients, regardless of literacy level, to access such resources to aid decision-making around undergoing breast surgery.

Reproductive Outcomes in Young Breast Cancer Survivors Treated (15-39) in Ontario, Canada.

We conducted a population-based, retrospective, matched-cohort study to examine the impact of breast cancer diagnosis and treatment on fertility outcomes. Relative risks of infertility, childbirth, premature ovarian insufficiency (POI; age < 40) and early menopause (age < 45) were calculated using modified Poisson regression. Our primary cohort included young women (15-39) with early stage BC diagnosed 1995-2014. Five cancer-free patients were matched to each BC patient by birth year and census subdivision. The BC cohort was further divided by treatment with chemotherapy vs. no chemotherapy treatment. 3903 BC patients and 19,515 cancer-free women. BC patients treated with chemotherapy were at increased risk of infertility (RR 1.81; 95% CI 1.60-2.04), and POI (RR 6.25; 95% CI 5.15-7.58) and decreased childbirth (RR 0.85; 95% CI 0.75-0.96), compared to women without cancer. BC patients who did not receive chemotherapy were also at increased risk of infertility (RR 1.80 95% CI 1.48-2.18) and POI (RR 2.12 95% CI 1.37-3.28). All young BC survivors face an increased risk of diagnosed infertility and POI relative to women without cancer, independent of chemotherapy. These results emphasize the importance of pre-treatment fertility counselling for young women diagnosed with BC.

Alcohol-associated Liver Disease Is Now the Most Common Indication for Liver Transplant Waitlisting Among Young American Adults.

BACKGROUND: Mortality from cirrhosis is increasing and is the highest among young adults with alcohol-associated liver disease (ALD). The aim of this study was to describe rates of liver transplant (LT) waitlisting stratified by age, sex, and cirrhosis etiology. METHODS: Retrospective population-based study from 2003 to 2018 using the Scientific Registry of Transplant Recipients database. Adults newly registered on the LT waitlist were included, and age at listing was dichotomized to ±40 y. Annual standardized incidence proportions of LT waitlisting by age group, sex, and etiology were calculated using census data. Changes in annual rates were described with Poisson regression. RESULTS: A total of 209 399 unique individuals were included, 10 326 (5%) <40 y at listing. In those <40 y of age, listing increased most for ALD (4-fold increase) followed by nonalcoholic fatty liver disease (NAFLD; 2-fold increase). Compared to young adult males, young females were more likely to be listed for ALD and less likely to be listed for NAFLD. In those ≥40 y of age, listings increased most for ALD (2-fold increase) and NAFLD (2-fold increase). Hepatitis C virus increased from 2003 to 2013 and declined post-2014 in the ≥40-y age group. CONCLUSIONS: LT waitlisting is increasing substantially in young Americans, driven primarily by ALD. These data support ongoing efforts to identify adolescents and young adults with early stages of ALD where interventions can be implemented to prevent the development of cirrhosis and liver-related complications.

Surgical practice patterns and outcomes in T2 and T3 gallbladder cancer: a population-based study.

BACKGROUND: The extent of resection required in advanced gallbladder cancer is controversial. We aimed to describe the management and outcomes in patients with resected stage T2 and T3 gallbladder cancer. METHODS: In this population-based study, all T2 and T3 gallbladder cancer cases from Jan. 1, 2002, to Mar. 31, 2012, were identified from the Ontario Cancer Registry; pathology reports were linked and abstracted. The type of resection was classified as extended (cholecystectomy + liver resection, with or without bile duct resection) or simple (cholecystectomy only). We used Kaplan-Meier survival analysis to model time to death and evaluated factors associated with overall survival using the Cox proportional hazards regression model. RESULTS: A total of 370 patients were included, 232 with T2 disease and 138 with T3 disease. The proportions who underwent extended resection were 24.1% (56/232) and 37.0% (51/138), respectively. The unadjusted 5-year overall survival rates for simple and extended resection were 39.7% and 49.5%, respectively, for T2 disease (p = 0.03), and 13.5% and 22.8%, respectively, for T3 disease (p = 0.05). In adjusted analysis, extended resection significantly improved overall survival among patients with T2 disease (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.30-0.97), whereas higher grade of differentiation, presence of lymphovascular invasion and positive lymph nodes led to worse survival. Extended resection was not associated with improved survival in the T3 group; however, in subgroup analysis stratified by lymph node status, a trend toward improved overall survival with extended resection was seen in node-negative patients (HR 0.20, 95% CI 0.03-1.06). CONCLUSION: Extended resection improved overall survival in T2 disease regardless of nodal status but appeared most beneficial in node-negative T3 disease. The finding that extended resection was offered only to a small proportion of eligible patients highlights the need for improved knowledge translation at national surgical meetings.

One Fraction Size Does Not Fit All: Patient Preferences for Hypofractionated Radiation Therapy From a Discrete Choice Experiment.

PURPOSE: Hypofractionated external beam radiation therapy (EBRT) is a standard of care option for localized prostate cancer. To inform clinical practice we quantified patients' preferences for convenience, efficacy, and toxicity risks, of conventional, moderate hypofractionation, and stereotactic radiation therapy regimens. METHODS AND MATERIALS: We used a discrete choice experiment with a voluntary sample consisting of patients treated with EBRT for localized prostate cancer at our academic cancer center. In 2019, 58 participants, mean (SD) age of 72.9 (7.1) years, agreed to complete an in-person 1:1 discrete choice experiment. Each participant made 12 choices between 2 unique EBRT scenarios, each described by 5 attributes: (1) treatment time; (2) fiducial markers; and risk of (3) prostate specific antigen recurrence; (4) acute and (5) late GI or GU toxicity. Patient preferences were estimated using mixed multinomial logistic regression, and prespecified subgroups with conditional logistic regression. RESULTS: All attributes were statistically significant, thus influenced participants' choices. Risks of prostate specific antigen recurrence (ß = -2.581), late (ß = -1.854), and acute (ß = -1.005) toxicity were most important to participants (P < .001 for each), followed by EBRT length (ß = -0.728; P = .017) and fiducial marker implantation (ß = -0.563; P = .004). Older (ß = -0.063; 95% confidence interval, -0.12, -0.01) and rural (ß = -0.083; 95% CI -0.14, -0.02) participants significantly preferred shorter EBRT and were less willing-to-extend treatment to reduce toxicity risk. CONCLUSIONS: Patients with prostate cancer place importance on EBRT attributes, and some are willing to trade-off increased risk of toxicity for improved convenience. Our findings promote shared clinical decision-making because patients are interested in learning about the trade-offs involved.

A descriptive cost-analysis of MYX.1/MCRN003, a phase 2 clinical trial evaluating high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone in relapsed and refractory multiple myeloma.

BACKGROUND: The prevalence of multiple myeloma is increasing and there is a need to evaluate escalating therapy costs (Canadian Cancer Statistics A, 2020). The MYX.1 phase II trial showed that high-dose weekly carfilzomib, cyclophosphamide, and dexamethasone (wKCD) is efficacious in relapsed and refractory disease. We conducted a descriptive cost analysis, from the perspective of the Canadian public healthcare system, using trial data. METHODS: The primary outcome was the mean total cost per patient. Resource utilization data were collected from all 75 trial patients over a trial time horizon. Costs are presented in Canadian dollars (2020). RESULTS: The cost of treatment was calculated from the time of patient (pt) enrollment until the second data lock. The mean total cost was $203 336.08/pt (range $17 891.27-$505 583.55) Canadian dollars (CAD, where 1 CAD = 0.67 Euro (EUR)) and $14 081.45/pt per cycle. The median number of cycles was 15. The predominant cost driver was the cost of chemotherapy accounting for an average of $179 332.78/pt or $12 419.17/pt per cycle. Carfilzomib acquisition accounted for the majority of chemotherapy costs - $162 471.65/pt or $11 251.50/pt per cycle. Fifty-six percent (56%) of patients had at least one hospitalization during the trial period with an average cost of $12 657.86 per hospitalization. Three patients developed thrombotic microangiopathy (TMA) with an average cost of $18 863.32/pt including the cost of hospitalizations and therapeutic plasma exchange. CONCLUSIONS: High-dose wKCD is an active triplet regimen for relapsed and refractory multiple myeloma (RRMM) associated with reduced total cost compared with twice-weekly carfilzomib-based regimens.

Factors predicting missing instruments in three cancer randomized clinical trials.

PURPOSE: Missing patient-reported outcome (PRO) data can seriously threaten the validity of randomized clinical trials (RCTs). Identifying which factors predict missing instruments may help researchers develop strategies to prevent it from happening. This study examined the association of factors with time to the first missing instrument after randomization in three cooperative group RCTs. METHODS: We performed descriptive analyses and Cox proportional hazards regressions for three RCTs selected from the Canadian Cancer Trials Group: MA17 (breast cancer), PR7 (prostate cancer), and LY12 (non-Hodgkin's lymphoma). The outcome was the time from randomization to the first missing instrument. Variables for 15 factors were used as covariates based on availability and previously-reported putative associations with missing PRO data. RESULTS: Nine percent of 1352 subjects on MA17, 37% of 923 subjects on PR7, and 59% of 477 subjects on LY12 had a missing instrument. Twenty-five percent of subjects on MA17 had first missing instrument within 4.6 years. The median time to first missing instrument was: not observed for MA17, 7.3 years for PR7, 0.12 years for LY12. Cox regression revealed statistically significant independent associations with outcome for only five factors: baseline age (PR7) and level of well-being (LY12), and centre level of activity (LY12), presence of post-graduate residency training program (MA17, PR7), and centre geographic location (PR7, LY12). CONCLUSION: Many factors reported to have association with missing instruments do not seem to predict time to the first missing instrument after randomization in RCTs. Context is important in understanding the few that may.

Clinical research associates experience with missing patient reported outcomes data in cancer randomized controlled trials.

BACKGROUND: Missing patient reported outcomes data threaten the validity of PRO-specific findings and conclusions from randomized controlled trials by introducing bias due to data missing not at random. Clinical Research Associates are a largely unexplored source for informing understanding of potential causes of missing PRO data. The purpose of this qualitative research was to describe factors that influence missing PRO data, as revealed through the lived experience of CRAs. METHODS: Maximum variation sampling was used to select CRAs having a range of experiences with missing PRO data from academic or nonacademic centers in different geographic locations of Canada. Semistructured interviews were audio-recorded, transcribed verbatim, and analyzed according to descriptive phenomenology. RESULTS: Eleven CRAs were interviewed. Analysis revealed several factors that influence missing PRO data that were organized within themes. PROs for routine clinical care compete with PROs for RCTs. Both the paper and electronic formats have benefits and drawbacks. Missing PRO data are influenced by characteristics of the instruments and of the patients. Assessment of PROs at progression of disease is particularly difficult. Deficiencies in center research infrastructure can contribute. CRAs develop relationships with patients that may help reduce missing PRO data. It is not always possible to provide sufficient time to complete the instrument. There is a need for field guidance and a motivation among CRAs to contribute their knowledge to address issues. CONCLUSION: These results enhance understanding of factors influencing missing PRO data and have important implications for designing operational solutions to improve data quality on cancer RCTs.

Variation in the UGT2B17 genotype, exemestane metabolism and menopause-related toxicities in the CCTG MAP.3 trial.

PURPOSE: To examine associations between the UGT2B17 gene deletion and exemestane metabolites, and commonly reported side effects (fatigue, hot flashes, and joint pain) among postmenopausal women participating in the MAP.3 chemoprevention trial. METHODS: The analytical samples for the UGT2B17 analysis comprised 1752 women on exemestane and 1721 women on placebo; the exemestane metabolite analysis included 1360 women on exemestane with one-year serum samples. Both the UGT2B17 gene deletion and metabolites were measured in blood. The metabolites were conceptualized as a ratio (17-DHE-Gluc:17-DHE). Symptoms were assessed using the CTCAE v4.0 at approximately 1-year intervals. Log-binomial regression was used to examine the associations between UGT2B17 deletion, exemestane metabolites and each side effect at 1 and up to 5-year follow-up, adjusting for potential confounders. RESULTS: Among individuals on exemestane with the UGT2B17 gene deletion (i.e., lower detoxification), a higher risk of severe fatigue (RR = 2.59 95% CI: 1.14-5.89) was observed at up to 5-year follow-up. Among individuals on placebo, those with the UGT2B17 gene deletion had a higher risk of any fatigue (RR = 1.39, 95% CI: 1.02-1.89) at year 1. A lower metabolite ratio (poor detoxification) was associated with a higher risk of any fatigue, hot flashes and joint pain at year 1 (fatigue: RR = 1.89, 95% CI: 1.16-3.09; hot flashes: RR = 1.77, 95% CI: 1.40-2.24; joint pain: RR = 2.05, 95% CI: 1.35-3.12); similar associations were observed at 5-year follow-up. CONCLUSION: Variation in the metabolism of exemestane through the UGT2B17-mediated pathway is associated with subsequent risk of commonly reported symptoms in MAP.3.

Baseline estrogen levels in postmenopausal women participating in the MAP.3 breast cancer chemoprevention trial.

OBJECTIVE: The aim of the study was to quantify baseline estradiol (E2) and estrone (E1) concentrations according to selected patient characteristics in a substudy nested within the MAP.3 chemoprevention trial. METHODS: E2 and E1 levels were measured in 4,068 postmenopausal women using liquid chromatography-tandem mass spectrometry. Distributions were described by age, years since menopause, race, body mass index (BMI), smoking status, and use and duration of hormone therapy using the Kruskal-Wallis test. Multivariable linear regression was also used to identify characteristics associated with estrogen levels. RESULTS: After truncation at the 97.5th percentile, the mean (SD)/median (IQR) values for E2 and E1 were 5.41 (4.67)/4.0 (2.4-6.7) pg/mL and 24.7 (14.1)/21 (15-31) pg/mL, respectively. E2 and E1 were strongly correlated (Pearson correlation [r] = 0.8, P < 0.01). The largest variation in E2 and E1 levels was by BMI; mean E2 and E1 levels were 3.5 and 19.1 pg/mL, respectively for women with BMI less than 25 and 7.5 and 30.6 pg/mL, respectively, for women with BMI greater than 30. E2 and E1 varied by age, BMI, smoking status, and prior hormone therapy in multivariable models (P < 0.01). CONCLUSIONS: There was large interindividual variability observed for E2 and E1 that varied significantly by participant characteristics, but with small absolute differences except in the case of BMI. Although the majority of participant characteristics were independently associated with E1 and E2, together, these factors only explained about 20% of the variation in E1 and E2 levels.

A geostatistical study of socioeconomic status (SES), rurality, seasonality and index test results as drivers of free private groundwater testing in southern Ontario, 2012-2016.

Approximately 12% of the Canadian population uses private wells for daily water consumption; however, well water testing rates are on the decline, resulting in an increased risk of waterborne acute gastrointestinal illness. To date, limited research has explored the determinants influencing well testing practices. Accordingly, the current study sought to investigate the drivers of "one-off" and repeat well water testing in southern Ontario during the 5-year period 2012-2016, using the worlds largest private groundwater testing data-frame. Data from >400,000 wells were geospatially integrated with all tests conducted by the provincial laboratory in southern Ontario. The Ontario Marginalization Index (ON-Marg) was used as a proxy measure of socioeconomic status (SES), with rurality, based on population density, season, and index (1st) test results assessed as effect modifiers. Multivariate analysis was undertaken using log-binomial regression. Approximately 27.5% of wells (n = 417,406) were tested during the study period, 66.7% of which were sampled more than once; 3% of all samples tested positive for E. coli (>0 colony forming unit/100 mL). In rural regions (<150 people/km2), wells located in low SES areas were 13% more likely to be tested compared to high SES areas (95% CI: 1.11, 1.15). In urban (>400 people/km2) and peri-urban regions (>150 and <400 people/km2), wells located in low SES areas were 14% (95% CI: 0.78, 0.95) and 15% (95% CI: 0.76, 0.94) less likely to be tested compared to high SES areas. Wells located in low SES areas were 6% more likely to be re-tested (95% CI: 1.04, 1.07). Positive index tests were associated with a 17% increased likelihood of repeat testing (95% CI: 1.16, 1.18). Accordingly, the authors conclude that location and SES are significant predictors of well water testing, with index test status being the most influential predictor of repeat well testing.

Age at natural menopause and physical functioning in postmenopausal women: the Canadian Longitudinal Study on Aging.

OBJECTIVE: The aim of this study was to evaluate the association between categories of age at natural menopause (ANM) and gait speed (slowness) and grip strength (weakness), common measures of physical functioning in older women. METHODS: We analyzed data from the Canadian Longitudinal Study on Aging, which included participants from seven cities across Canada collected in 2012. The sample was restricted to women who reported to have entered menopause (N = 9,920). Women who had a hysterectomy before menopause were excluded since the age at which this surgical procedure was performed was not available. ANM was categorized into five groups: less than 40 (premature), 40 to 44 (early), 45 to 49, 50 to 54, and more than 54. We conducted linear regressions to assess the association between ANM and gait speed (m/s) and grip strength (kg) adjusting for participant age, education, body mass index, smoking, use of hormone therapy, height, and province of residence. RESULTS: Mean ANM was 49.8 (95% confidence interval [CI]: 49.7-50.0), with 3.8% of women having a premature menopause; the average gait speed was 0.98 m/s (standard deviation: 0.22), the average grip strength was 26.6 kg (standard deviation: 6.39). Compared to women with ANM of 50 to 54, women with premature menopause had 0.054 m/s (95% CI -0.083, -0.026) lower gait speed when adjusting for age and study site. In the fully adjusted model, the association was attenuated, 0.032 m/s (95% CI -0.060, -0.004). ANM was not associated with grip strength. CONCLUSION: Our study suggests that premature menopause (<40 years) may be associated with lower gait speed (slowness) among Canadian women. No association was observed between ANM and grip strength. Future studies should include a life course approach to evaluate whether social and biological pathways modify the association between age at menopause and physical function in populations from different contexts.

Genetic variants in genes related to inflammation, apoptosis and autophagy in breast cancer risk.

BACKGROUND: Inflammation contributes to breast cancer development through its effects on cell damage. This damage is usually dealt with by key genes involved in apoptosis and autophagy pathways. METHODS: We tested 206 single nucleotide polymorphisms (SNPs) in 54 genes related to inflammation, apoptosis and autophagy in a population-based breast cancer study of women of European (658 cases and 795 controls) and East Asian (262 cases and 127 controls) descent. Logistic regression was used to estimate odds ratios for breast cancer risk, and case-only analysis to compare breast cancer subtypes (defined by ER/PR/HER2 status), with adjustment for confounders. We assessed statistical interactions between the SNPs and lifestyle factors (smoking status, physical activity and body mass index). RESULTS AND CONCLUSION: Although no SNP was associated with breast cancer risk among women of European descent, we found evidence for an association among East Asians for rs1800925 (IL-13) and breast cancer risk (OR = 2.08; 95% CI: 1.32-3.28; p = 0.000779), which remained statistically significant after multiple testing correction (padj = 0.0350). This association was replicated in a meta-analysis of 4305 cases and 4194 controls in the Shanghai Breast Cancer Genetics Study (OR 1.12, 95% CI: 1.03-1.21, p = 0.011). Further, we found evidence of an interaction between rs7874234 (TSC1) and physical activity among women of East Asian descent.

Disparities in diagnosis of advanced melanoma: a population-based cohort study.

BACKGROUND: International studies have observed inequities in stage at diagnosis of melanoma. As this has not been sufficiently studied in Canada, the purpose of this study was to investigate whether there are disparities in the diagnosis of advanced-thickness melanoma in the province of Ontario. METHODS: In this retrospective population-based cohort study, we obtained, abstracted and linked pathology reports for a 65% random sample of all cases of invasive cutaneous melanoma in Ontario from 2007 to 2012 in the Ontario Cancer Registry. Cases without pathology reports or with unreported thickness were excluded from the primary analysis. Associations between advanced melanoma (thickness > 2.0 mm) and patient, health-system and tumour factors were described and analyzed using multivariable modified Poisson regression. RESULTS: In total, 8042 patients had histologically confirmed melanoma and thickness information. Of these, 46.7% (n = 3755) were female, the median age at diagnosis was 62 years and 25.7% (n = 2069) had advanced melanoma. In multivariate analyses, advanced age (relative risk [RR] 1.53; 95% confidence interval [CI] 1.37-1.72), male sex (RR 1.12, 95% CI 1.05-1.20), lowest socioeconomic status quintile (RR 1.24; 95% CI 1.12-1.38) and health region (RR range 0.92-1.34, p = 0.005 for variable) were significantly associated with advanced melanoma. Presence of ulceration significantly modified many of these associations. INTERPRETATION: Disparate rates of advanced melanoma according to patient and health system factors suggest there may be inequitable access to timely diagnosis of melanoma in Ontario. This highlights a potential opportunity for system improvement to ensure timely and equitable access to melanoma care.

Associations between occupational exposure to benzene, toluene and xylene and risk of lung cancer in Montréal.

BACKGROUND: Benzene, toluene and xylene (BTX) are aromatic hydrocarbons with inconclusive evidence of lung carcinogenicity. The aim of this research was to assess the associations between occupational exposures to BTX agents and lung cancer. METHODS: In a population-based case-control study of lung cancer, occupational histories were obtained and exposures were assessed by experts. Unconditional multivariate logistic regression was used to estimate ORs and 95% CIs, among men, between various metrics of occupational exposure to BTX and lung cancer, while adjusting for established and possible risk factors. RESULTS: Considerable overlap was found between occupational exposure to BTX, where the majority of exposed participants were exposed to all three chemicals. Lung cancer was associated with exposure to benzene (OR=1.35; 95% CI 0.99 to 1.84), toluene (OR=1.31; 95% CI 0.99 to 1.74) and xylene (OR=1.44; 95% CI 1.03 to 2.01). While these results were adjusted for smoking and other recognised and possible lung cancer risk factors, they were not mutually adjusted among the three BTX agents. CONCLUSIONS: Our study provides suggestive evidence that occupational exposure to one or more of the BTX agents may be associated with lung cancer.

A systematic review and development of a classification framework for factors associated with missing patient-reported outcome data.

BACKGROUND/AIMS: Missing patient-reported outcome data can lead to biased results, to loss of power to detect between-treatment differences, and to research waste. Awareness of factors may help researchers reduce missing patient-reported outcome data through study design and trial processes. The aim was to construct a Classification Framework of factors associated with missing patient-reported outcome data in the context of comparative studies. The first step in this process was informed by a systematic review. METHODS: Two databases (MEDLINE and CINAHL) were searched from inception to March 2015 for English articles. Inclusion criteria were (a) relevant to patient-reported outcomes, (b) discussed missing data or compliance in prospective medical studies, and (c) examined predictors or causes of missing data, including reasons identified in actual trial datasets and reported on cover sheets. Two reviewers independently screened titles and abstracts. Discrepancies were discussed with the research team prior to finalizing the list of eligible papers. In completing the systematic review, four particular challenges to synthesizing the extracted information were identified. To address these challenges, operational principles were established by consensus to guide the development of the Classification Framework. RESULTS: A total of 6027 records were screened. In all, 100 papers were eligible and included in the review. Of these, 57% focused on cancer, 23% did not specify disease, and 20% reported for patients with a variety of non-cancer conditions. In total, 40% of the papers offered a descriptive analysis of possible factors associated with missing data, but some papers used other methods. In total, 663 excerpts of text (units), each describing a factor associated with missing patient-reported outcome data, were extracted verbatim. Redundant units were identified and sequestered. Similar units were grouped, and an iterative process of consensus among the investigators was used to reduce these units to a list of factors that met the guiding principles. The list was organized on a framework, using an iterative consensus-based process. The resultant Classification Framework is a summary of the factors associated with missing patient-reported outcome data described in the literature. It consists of 5 components (instrument, participant, centre, staff, and study) and 46 categories, each with one or more sub-categories or examples. CONCLUSION: A systematic review of the literature revealed 46 unique categories of factors associated with missing patient-reported outcome data, organized into 5 main component groups. The Classification Framework may assist researchers to improve the design of new randomized clinical trials and to implement procedures to reduce missing patient-reported outcome data. Further research using the Classification Framework to inform quantitative analyses of missing patient-reported outcome data in existing clinical trials and to inform qualitative inquiry of research staff is planned.

Lifetime moderate-to-vigorous physical activity and ER/PR/HER-defined post-menopausal breast cancer risk.

PURPOSE: To assess the relationship of moderate-to-vigorous physical activity (MVPA) in leisure-time, household, and occupational domains across the total lifetime and in four age periods with breast cancer risk, as defined by estrogen receptor (ER)/progesterone receptor (PR) status and ER/PR/human epidermal growth factor-2 (HER2) status, among post-menopausal women. METHODS: Data were from 692 women with incident breast cancer and 644 controls in the Canadian Breast Cancer Study, a case-control study of women aged 40-80 years in British Columbia and Ontario. Mean metabolic equivalent (MET)-hours/week for questionnaire-assessed leisure-time, household, and occupational MVPA were calculated for the total lifetime and four age periods (12-17, 18-34, 45-49, and ≥50 years). Odds ratios (ORs) for the relationships between domain-specific MVPA at each lifetime period and risks of ER/PR-defined and ER/PR/HER2-defined breast cancers were estimated using polytomous logistic regression. Trend tests for dose-response relationships were calculated for the ORs across increasing tertiles of mean MET-hours/week of MVPA. RESULTS: Total lifetime leisure-time MVPA was associated with reduced risk of ER-/PR- breast cancer in a dose-response fashion (p trend = 0.014). In contrast, total lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer (p trend < 0.001). When further stratified by HER2 status, the effect of leisure-time MVPA appeared confined to HER2- breast cancers, and the effect of household MVPA did not differ according to HER2 status. Similar trends were observed when stratified by age period. CONCLUSIONS: Lifetime leisure-time MVPA appeared to be associated with reduced risk of ER-/PR-/HER2- breast cancers and lifetime household MVPA was associated with reduced risk of ER+ and/or PR+ breast cancer, regardless of HER2 status.

Factors Associated With Early Discontinuation of Study Treatment in the Mammary Prevention.3 Breast Cancer Chemoprevention Trial.

Purpose Aromatase inhibitors are established breast cancer chemoprevention interventions. However, nonadherence remains a significant challenge. We investigated the association between worsening menopause-specific quality of life, baseline participant characteristics, and early treatment discontinuation within the Mammary Prevention.3 (MAP.3) breast cancer prevention trial. Methods In the MAP.3 randomized, placebo-controlled trial evaluating exemestane, participants completed the Menopause-Specific Quality of Life Questionnaire (MENQOL) at entry and at 6 months. Multivariable log-binomial regression was used to assess the associations of baseline participant characteristics and clinically meaningful worsening in menopause-specific quality of life (QOL) with treatment discontinuation at 1 year. Results Of the 4,501 participants eligible for this analysis, 724 (17%) discontinued assigned treatment within the first year of random assignment of treatment (19% of the exemestane group and 13% of the placebo group). Between 19% and 35% of women experienced a clinically meaningful worsening in the vasomotor, sexual, physical, and psychosocial domains of the MENQOL within 6 months of treatment initiation. Regardless of receiving exemestane or not, experiencing a worsening in any MENQOL domain or, especially, overall menopause-specific QOL, was associated with early treatment discontinuation (relative risk, 1.79; 95% CI, 1.53 to 2.10 for overall worsening). Assignment to exemestane, having a smoking history, and current employment also were significantly associated with early discontinuation. Conclusion Negative changes in menopause-specific QOL influence a woman's decision to stop chemoprevention therapy. Attention to such symptoms may improve QOL and potentially improve chemoprevention adherence.

Epidemiologic Evaluation of Human Papillomavirus Type Competition and the Potential for Type Replacement Post-Vaccination.

BACKGROUND: Millions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females. METHODS: Valid HPV DNA typing information was available from five epidemiological studies conducted in Canada and Brazil (n = 14,685; enrollment across studies took place between1993 and 2010), which used similar consensus-primer PCR assays, capable of detecting up to 40 HPV types. A total of 38,088 cervicovaginal specimens were available for inclusion in our analyses evaluating HPV type-type interactions involving vaccine-targeted types (6, 11, 16, and 18), and infection with each of the other HPV types. RESULTS: Across the studies, the average age of participants ranged from 21.0 to 43.7 years. HPV16 was the most common type (prevalence range: 1.0% to 13.8%), and in general HPV types were more likely to be detected as part of a multiple infection than as single infections. In our analyses focusing on each of the vaccine-targeted HPV types separately, many significant positive associations were observed (particularly involving HPV16); however, we did not observe any statistically significant negative associations. CONCLUSIONS: Our findings suggest that natural HPV type competition does not exist, and that type replacement is unlikely to occur in vaccinated populations.