Association of metabolic syndrome conditions with risk of second primary uterine cancer in breast cancer survivors.

PURPOSE: Uterine cancer risk is high in breast cancer survivors. Although breast cancer and uterine cancer share some common epidemiological risk factors, association of metabolic syndrome with incident uterine cancer in breast cancer survivors is under-studied. We evaluated the association of metabolic syndrome conditions with second primary uterine cancer in breast cancer survivors. METHODS: In this retrospective cohort study, 37,303 breast cancer patients diagnosed between 2008 and 2020 at Kaiser Permanente Southern California, an integrated healthcare system, were included. Data on cancer-related variables, sociodemographic, and clinical variables were extracted from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry and electronic health records, as appropriate. Patients were followed from breast cancer diagnosis until 12/31/2021 for incident uterine cancer. Proportional hazards regression was used to report association [HR (95% CI)] between metabolic conditions and uterine cancer. RESULTS: More than half (53.1%) of the breast cancer survivors had 1-2 metabolic conditions; 19.4% had 3 + , while 27. 5% had no metabolic conditions. Median time to follow-up was 5.33 years and 185 (0.5%) patients developed second primary uterine cancer. Obesity was associated with an elevated uterine cancer risk in the adjusted model [HR (95% CI) 1.64 (1.20-2.25)]. Having 1-2 metabolic conditions (versus none) was not associated with increased uterine cancer risk [adjusted HR (95% CI) 1.24 (0.85-1.82)]; however, there was an increased uterine cancer risk with 3 + metabolic conditions [adjusted HR (95% CI) 1.82 (1.16-2.87)]. CONCLUSION: Although not statistically significant, we found a trend demonstrating greater uterine cancer risk by increasing numbers of metabolic syndrome conditions in breast cancer survivors.

Investigating Mortality Disparities Among Insured Patients With Colon Cancer Treated in an Integrated Health care System and Other Private Settings.

BACKGROUND: Lower socioeconomic status (SES) affects health care delivery and is associated with worse outcomes. Integrated healthcare systems (IHS) may help reduce barriers to health care and affect outcomes. Our aim was to compare outcomes of colon cancer cases diagnosed at the largest IHS in California, Kaiser Permanente Southern California (KPSC), to other insured patients (OI) to determine how SES influences mortality. METHODS: This retrospective cohort study included insured adults in southern California diagnosed with colon cancer between 2009 and 2014, using data from the California Cancer Registry, and followed through 2017. Main outcome was all-cause mortality. Person-year mortality rates were calculated for two groups, KPSC and OI. Multivariable hazard ratios were calculated for association between SES quintiles and mortality. RESULTS: Total of 15 923 patients were diagnosed with colon cancer, 4195 patients (26.3%) within KPSC and 11 728 patients (73.7%) in OI. The overall mortality rate per 1000 person-years (PY) was lower in KPSC [103.8/1000 PY (95% CI:98.5-109.3)] compared to OI [139.3/1000 PY (95% CI:135.2-143.4)]. Compared to the highest SES group, the lowest SES group did not experience higher mortality risk in the KPSC population, after adjusting for race/ethnicity and other factors (HR, 95% CI = 1.13, .93-1.38). However, in OI patients, lowest and lower-middle SES groups had higher mortality risk compared to the highest SES group (HR, 95% CI = 1.26, 1.13-1.40 and 1.28, 1.16-1.41, respectively). DISCUSSION: Lower SES was associated with higher mortality risk within the OI group; however, within KPSC no such association was observed. Care coordination in IHS settings mitigate SES-related mortality differences.

Disparities in melanoma-specific mortality by race/ethnicity, socioeconomic status, and health care systems.

BACKGROUND: Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. OBJECTIVE: We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. METHODS: Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). RESULTS: Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. LIMITATIONS: Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. CONCLUSIONS: Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.

Associations of Health-Related Quality of Life and Sleep Disturbance With Cardiovascular Disease Risk in Postmenopausal Breast Cancer Survivors.

BACKGROUND: Breast cancer (BC) survivors are at an increased risk of long-term cardiovascular disease (CVD), often attributed to cancer treatment. However, cancer treatment may also negatively impact health-related quality of life (HRQoL), a risk factor of CVD in the general population. OBJECTIVE: We examined whether sleep disturbance, and physical or mental HRQoL were associated with CVD risk in BC survivors. METHODS: We conducted a longitudinal analysis in the Women's Health Initiative of postmenopausal women given a diagnosis of invasive BC during follow-up through 2010 with no history of CVD before BC. The primary outcome was incident CVD, defined as physician-adjudicated coronary heart disease or stroke, after BC. Physical and mental HRQoL, measured by the Short-Form 36 Physical and Mental Component Summary scores, and sleep disturbance, measured by the Women's Health Initiative Insomnia Rating Scale, were recorded post BC. Time-dependent Cox proportional hazards models were used starting at BC diagnosis until 2010 or censoring and adjusted for relevant confounders. RESULTS: In 2884 BC survivors, 157 developed CVD during a median follow-up of 9.5 years. After adjustment, higher Physical Component Summary scores were significantly associated with a lower risk of CVD (hazard ratio, 0.90 [95% confidence interval, 0.81-0.99]; per 5-point increment in Physical Component Summary). No associations with CVD were found for Mental Component Summary or Insomnia Rating Scale. CONCLUSION: In BC survivors, poor physical HRQoL is a significant predictor of CVD. IMPLICATIONS FOR PRACTICE: Our findings highlight the importance for nurses to assess and promote physical HRQoL as part of a holistic approach to mitigating the risk of CVD in BC survivors.

Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study.

Importance: Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. Objective: To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. Design, Setting, and Participants: The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. Exposures: Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. Results: A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). Conclusions and Relevance: These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

The Influence of Medical Comorbidities on Survival Disparities in a Multiethnic Group of Patients with De Novo Metastatic Breast Cancer.

BACKGROUND: The influence of common medical comorbidities on mortality and racial/ethnic disparities in mortality among women with metastatic breast cancer remains largely unknown. METHODS: In this longitudinal study, women with newly diagnosed stage IV breast cancer were identified in a large, diverse, integrated healthcare delivery system from January 2009 to December 2017 (n = 995) and followed through December 31, 2018, for all-cause (overall) and breast cancer-specific mortality via electronic health records. We computed overall and breast cancer-specific mortality rates by race/ethnicity and Elixhauser comorbidity index (ECI). Multivariable-adjusted hazard ratios (HR) assessing the influence of race/ethnicity and comorbidity status on overall and breast cancer-specific mortality were estimated using proportional hazards regression adjusted for age, breast cancer subtype, geocoded income, and palliative cancer treatments. RESULTS: Nearly 17% of this cohort had diabetes and 45% had hypertension. Overall, 644 deaths occurred in the cohort (median follow-up time of 1.8 years), of which 88% were breast cancer related. The risk of overall mortality was increased in Asian/Pacific Islander (PI; adjusted HR = 1.45; 95% CI, 1.10-1.92) and African American/Black women (adjusted HR = 1.34; 95% CI, 1.02-1.76) when compared with white women. Women with more comorbidities (ECI ≥ 5) had more than 3-fold higher overall mortality rate than those without any comorbidities [602/1,000 person-year (PY) vs. 175/1,000 PY]. Similar associations were found for breast cancer-specific mortality. CONCLUSIONS: Medical comorbidities are associated with an increased risk of overall mortality among women with de novo metastatic disease and may influence racial/ethnic disparities in mortality. IMPACT: Optimizing the management of medical comorbidities in metastatic breast cancer patients may also help reduce disparities in breast cancer-related mortality.

Influence of health care systems on mortality in adult patients with cancer.

OBJECTIVES: We compared all-cause mortality in insured patients with cancer who were diagnosed in Kaiser Permanente Southern California (KPSC), the largest integrated health care delivery system in southern California, with that in patients diagnosed in hospitals that serve other private insurance (OPI) plans. STUDY DESIGN: Retrospective cohort study. METHODS: Using the California Cancer Registry, we conducted a cohort analysis of all insured adults diagnosed between 2009 and 2014 with 8 common cancers (breast, prostate, lung, colon, melanoma, endometrium, kidney, and bladder) and followed them through December 2017. The cohort comprised 164,197 patients with cancer. We calculated person-year mortality rates by health care system (KPSC and OPI), and we estimated adjusted HRs for the association between overall mortality and health care system using Cox proportional hazards models accounting for race/ethnicity, demographics, cancer site, tumor characteristics, payer, cancer treatments, and socioeconomic status. RESULTS: We observed 41,727 deaths during the 9 years of follow-up. We found that the patients diagnosed in KPSC had lower overall mortality rates than in the OPI group, a difference that also held within each age category, racial/ethnic group, and stage at diagnosis. In multivariable models adjusting for relevant covariates, African American/Black patients (adjusted HR, 1.14; 95% CI, 1.06-1.21) and Hispanic patients (adjusted HR, 1.23; 95% CI, 1.16-1.30) in the OPI group had dramatically higher mortality risks than those diagnosed in KPSC. CONCLUSIONS: Among insured patients with cancer in southern California, those diagnosed within KPSC had lower overall mortality compared with the OPI group. Furthermore, this protective effect was greatest for African American/Black patients and Hispanic patients.

SARS-CoV-2 Testing, Positivity Rates, and Healthcare Outcomes in a Cohort of 22,481 Breast Cancer Survivors.

PURPOSE: As health inequities during the pandemic have been magnified, we evaluated how use of SARS-CoV-2 testing differed by race or ethnicity in a large cohort of breast cancer survivors and examined the correlates of testing positive. METHODS: We conducted a retrospective cohort study of 22,481 adult breast cancer survivors who were active members of a large California integrated healthcare plan in 2020. We collected data on their breast cancer diagnosis, comorbidity, and demographic characteristics. We examined SARS-CoV-2 testing utilization between March 2020 and September 2020 by race or ethnicity, comorbidity, and other patient characteristics. We also examined the correlates of a having a positive SARS-CoV-2 test result. We conducted bivariable and multivariable logistic regression to identify correlates of testing utilization and test positivity. RESULTS: Of these 22,481 women, 3,288 (14.6%) underwent SARS-CoV-2 testing. The cohort included 51.8% women of color. Of the 3,288 tested, 264 (8.0%) women had a positive test result. In multivariable analyses, Latinx survivors were more likely (adjusted odds ratio [OR], 1.23; 95% CI, 1.12 to 1.34) to undergo testing than White survivors; however, Asian or Pacific Islander survivors were 16% less likely to get tested (adjusted OR, 0.84; 95% CI, 0.75 to 0.94). Compared to White survivors, Latinx survivors were 3.5 times (adjusted OR, 3.47; 95% CI, 2.52 to 4.77) and Asian or Pacific Islander or Other survivors were 2.2-fold (adjusted OR, 2.23; 95% CI, 1.49 to 3.34) more likely to test positive. Being overweight (adjusted OR, 1.83; 95% CI, 1.24 to 2.72) or obese (adjusted OR, 2.04; 95% CI, 1.39 to 2.98) were also strongly associated with SARS-CoV-2 positivity. CONCLUSION: Even in an integrated healthcare system, Asian or Pacific Islander patients were less likely to undergo SARS-CoV-2 testing than White survivors, but more likely to test positive. Additionally, Latinx ethnicity and high body mass index were strongly correlated with a greater odds of SARS-CoV-2 test positivity.

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer.

PURPOSE: Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients. METHODS: A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis. RESULTS: ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each individual complication compared to non-use. CONCLUSION: ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

Medication adherence, molecular monitoring, and clinical outcomes in patients with chronic myelogenous leukemia in a large HMO.

OBJECTIVE: Our objective was to examine the association between adherence to tyrosine kinase inhibitors (TKIs) and molecular monitoring and the risk of disease progression or mortality among patients with chronic phase chronic myeloid leukemia (CML). DESIGN: We assembled a retrospective cohort of patients with CML (chronic phase, no prior cancer history, and confirmed to be Philadelphia chromosome positive) using data from electronic health records and chart reviews. Medication possession ratio (MPR) was used to measure drug adherence. SETTING: A large, community-based, integrated health plan in Southern California. PARTICIPANTS: The cohort consisted of 245 adult patients (≥18 years old) with Philadelphia positive chronic phase CML diagnosed from 2001 to 2012 and followed through 2013. MAIN OUTCOME MEASURES: In survival analyses, we examined the association of TKI adherence (MPR) and polymerase chain reaction (PCR) monitoring test frequency with the composite clinical outcome, progression to accelerated phase disease-blast crisis or mortality (progression-free survival). The cohort was followed for a maximum of 13 years (median 4.6 years). RESULTS: Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and the mean MPR was 88% (SD 18%). Virtually all patients (96%) started on imatinib. The rates of progression to accelerated phase-blast crisis and mortality were lower in patients with greater TKI adherence (20.4/1000 person-years) versus lower adherence (27.0/1000 person-years). Patients who underwent PCR monitoring had a significantly reduced risk of progression or mortality, which was seen in patients with high and low TKI adherence status from both the groups (hazard ratio [HR] 0.07 [95% CI 0.03-0.19 if MPR >90%] and HR 0.70 [95% CI 0.02-0.21 if MPR<90%]). CONCLUSION: Our results suggest that close clinical monitoring, which includes PCR monitoring in patients with high and low TKI drug adherence, is associated with a lower risk of progression or mortality.

Use of androgen deprivation therapy as salvage treatment after primary therapy for clinically localized prostate cancer.

PURPOSE: The optimal use of androgen deprivation therapy as salvage treatment (sADT) for men after initial prostatectomy or radiotherapy for clinically localized prostate cancer is undefined. We describe patterns of sADT use and investigate clinical and sociodemographic characteristics of insured men who received sADT versus surveillance in managed care settings. METHODS: Using comprehensive electronic health records and cancer registry data from three integrated health plans, we identified all men with newly diagnosed clinically localized prostate cancer between 1995 and 2009 who received either prostatectomy (n = 16,445) or radiotherapy (n = 19,531) as their primary therapy. We defined sADT based on the timing of ADT following primary therapy and stage of cancer. We fit Cox proportional hazard models to identify sociodemographic characteristics and clinical factors associated with sADT. RESULTS: With a median follow-up of 6 years (range 2-15 years), 13 % of men who underwent primary prostatectomy or radiotherapy received sADT. After adjusting for selected covariates, sADT was more likely to be used in men who were older (e.g., HR 1.70, 95 % CI 1.48-1.96 or HR 1.33, 95 % CI 1.17-1.52 for age 70+ relative to age 35-59 for primary prostatectomy or radiotherapy, respectively), were African-American, had a short PSA doubling time, had a higher pre-treatment risk of progression, had more comorbidities, and received adjuvant ADT for initial disease. CONCLUSIONS: In men with localized prostate cancer in community practice initially treated with prostatectomy or radiotherapy, sADT after primary treatment was more frequent for men at greater risk of death from prostate cancer, consistent with practice guidelines.

Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors.

BACKGROUND: The risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain. METHODS: The authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results-affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional-hazards models. RESULTS: Endometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence. CONCLUSIONS: In a community-based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen-associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association.

Treatment patterns for ductal carcinoma in situ from 2000-2010 across six integrated health plans.

Considerable debate exists about the optimal treatment of ductal carcinoma in situ (DCIS). Using electronic data sources, we examined first course treatment patterns among women aged 18 years and older diagnosed with DCIS between 2000-2010 from six Kaiser Permanente (KP) regions. We calculated the proportion of patients receiving breast conserving surgery (BCS), BCS plus radiation therapy, unilateral mastectomy, bilateral mastectomy, and hormone therapy. Multinomial logistic regression was used to assess the association between patient characteristics and treatment. We included 9,437 women: 1,086 (11.5%) African-American; 1,455 (15.4%) Asian; 918 (9.7%) Hispanic; and 5,978 (63.3%) non-Hispanic white. Most cases (42.2%) received BCS plus radiation as their initial treatment. Nearly equal numbers of women received BCS without radiation (28.5%) or unilateral mastectomy (24.6%). Use of bilateral mastectomy was uncommon (4.7%), and most women (72.2%) did not receive hormone therapy has part of their first course treatment. We observed statistically significant differences in treatment patterns for DCIS by KP region and patient age. Predictably, nuclear grade and the presence of comorbidities were associated with first course treatment for DCIS. We observed statistically significant increases in BCS plus radiation therapy and bilateral mastectomy over time. Although still uncommon, the frequency of bilateral mastectomy increased from 2.7% in 2000 to 7.0% in 2010. We also observed differences in treatment by race/ethnicity. Our findings help illustrate the complex nature of DCIS treatment in the United States, and highlight the need for evidence based guidelines for DCIS care.

Effectiveness of primary androgen-deprivation therapy for clinically localized prostate cancer.

PURPOSE: Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. METHODS: We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. RESULTS: Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). CONCLUSION: We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.

Fracture risk in older, long-term survivors of early-stage breast cancer.

OBJECTIVES: To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. DESIGN: A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women. SETTING: Six integrated healthcare systems. PARTICIPANTS: Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5 years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. MEASUREMENTS: Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. RESULTS: No difference was observed in fracture rates between groups (hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.9-1.3). The protective effect of tamoxifen was not statistically significant (HR = 0.9, 95% CI = 0.6-1.2). CONCLUSION: Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use.

Impact of breast cancer subtypes and treatment on survival: an analysis spanning two decades.

BACKGROUND: We investigated the impact of breast cancer molecular subtypes and treatment on survival in a cohort of medically insured women followed for more than 20 years. METHODS: We examined 934 female members of an integrated health care delivery system newly diagnosed with invasive breast cancer between 1988 and 1995 and followed them through 2008. Tumors were classified into four molecular subtypes on the basis of their expression profile: luminal A; luminal B; basal-like; and HER2-enriched. We followed women from the surgery date to death, health plan disenrollment, or study's end. HR and 95% confidence intervals (CI) were fit using Cox proportional hazards models adjusting for cancer treatments and tumor characteristics. RESULTS: A total of 223 (23.9%) women died because of breast cancer during the 21-year study period. Compared with women with luminal A tumors, women with HER2-enriched (HR 2.56, 95% CI 1.53-4.29) and luminal B tumors (HR 1.96, 95% CI: 1.08-3.54) had roughly a two-fold increased adjusted risk of breast cancer mortality. In addition, the survival curves suggest that risk of late mortality persists in women with luminal A tumors. CONCLUSION: Among women with health care coverage, molecular subtypes were important predictors of breast cancer mortality. Women with HER2-enriched tumors and luminal B subtypes had the poorest survival despite adjusting for important covariates. IMPACT: In a cohort followed for more than 20 years, women with HER2-enriched tumors had worse survival, but interestingly, the survival curve for women with luminal A tumors continued to steadily decline after 10 years of follow-up.

Ten-year risk of diagnostic mammograms and invasive breast procedures after breast-conserving surgery for DCIS.

BACKGROUND: Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known. METHODS: We identified 2948 women with DCIS who were treated with BCS from 1990 to 2001 and followed for up to 10 years at three integrated health-care delivery systems. We calculated the percentages of diagnostic mammograms and ipsilateral invasive procedures following the initial breast excision to treat DCIS, estimated the 10-year cumulative incidence of these procedures, and determined hazard ratios for both types of procedures with Cox regression modeling. All statistical tests were two-sided. RESULTS: Over 10 years, 907 women (30.8%) had 1422 diagnostic mammograms and 1813 (61.5%) had 2305 ipsilateral invasive procedures. Diagnostic mammograms occurred in 7.3% of women in the first 6 months and continued at a median annual rate of 4.3%. Ipsilateral invasive procedures occurred in 51.5% of women in the first 6 months and continued at a median annual rate of 3.1%. The estimated 10-year cumulative risk of having at least one diagnostic mammogram after initial DCIS excision was 41.0% (95% confidence interval [CI] = 38.5% to 43.5%); at least one invasive procedure, 65.7% (95% CI = 63.7% to 67.8%); and either event, 76.1% (95% CI = 74.1% to 78.1%). Excluding events in the first 6 months following initial DCIS excision, corresponding risks were 36.4% (95% CI = 33.8% to 39.0%) for diagnostic mammograms, 30.4% (95% CI = 26.9% to 33.8%) for invasive procedures, and 49.5% (95% CI = 45.6% to 53.5%) for either event. CONCLUSIONS: Women with DCIS treated with BCS continue to have diagnostic and invasive breast procedures in the conserved breast over an extended period. The frequency of ongoing diagnostic breast evaluations should be included in discussions about treatment.

Treatment of ductal carcinoma in situ among patients cared for in large integrated health plans.

OBJECTIVE: To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. STUDY DESIGN: Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. METHODS: We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. chi(2) Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. RESULTS: We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31-0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48-0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. CONCLUSION: Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods.

Statin use and risk of colorectal cancer in a cohort of middle-aged men in the US: a prospective cohort study.

BACKGROUND: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer. OBJECTIVE: To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization. METHODS: We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45-69 years who enrolled in the California Men's Health Study in 2002-3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders. RESULTS: During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of >or=5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers. CONCLUSION: These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for >or=5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.