Kaiser Permanente Northern California Cancer Research Articles

Treatment rates and reasons for non-treatment in a real-world cohort of patients with pancreatic cancer.

e13554 Background: The proportion of patients who receive treatment for pancreatic ductal adenocarcinoma (PDAC) and reasons for non-treatment in real-world patient populations are poorly understood. Our study aims to determine treatment rates, predictors for non-treatment, and the rationale for declining treatment in a well-defined, diverse, community-based patient population. Methods: We identified all adult patients with PDAC (n = 3852) between 2010 and 2020 through the Kaiser Permanente Northern California Cancer Registry. Patients were stratified by age and tumor characteristics to determine rates of oncologic therapy. Multivariable logistic regression was used to assess how covariates were associated with receiving treatment. A detailed chart review of all patients ≤ 65 years and a random sample of 100 patients > 65 years with non-metastatic disease who did not receive treatment was performed to better understand the reasons for non-treatment. A random sample of 20 patients with metastatic disease who did not receive treatment were also reviewed. Results: Of patients with PDAC, 77.7% of patients with non-metastatic and 56.2% with metastatic disease received any cancer-directed treatment. A multivariate analysis showed no statistically significant differences by race/ethnicity or gender. Increasing age was a significant negative predictor of treatment. Charlson comorbidity index (CCI) did not influence treatment rates in patients with non-metastatic PDAC, but in patients with metastatic disease those with CCI 3+ had a decreased odds of receiving treatment. Of patients ≤ 65 years with non-metastatic disease, 90.3% were seen by an oncologist, and of those patients 89.3% were offered treatment. The primary reason for declining treatment was patient/family preference in 80.8%, followed by PDAC-related frailty in 11.5%, and medical comorbidity/other malignancy in 7.69%. Similarly, of patients > 65 years with non-metastatic disease, the majority were also seen by an oncologist, offered treatment, and declined due to personal preference. The same trends were noted in patients with metastatic PDAC. Conclusions: A significant proportion of patients with PDAC did not receive cancer-directed treatment in a real-world, community-based patient population, and this was more likely for patients with metastatic disease. Race and gender did not influence whether patients received treatment in this fully insured patient population and comorbidity had a small effect. Patients of increasing age, however, were less likely to receive treatment. Most patients who did not initiate treatment did so primarily due to patient/family preference despite being offered cancer-directed therapy by their treatment team. These findings may help guide the development and utilization of patient decision-aids in PDAC to improve goal concordant care that accounts for patients’ preferences and values.

Patients with cancer symptom and physical function reporting by caregivers as predictors of adverse clinical outcomes.

12026 Background: Informal caregivers are essential partners in the delivery of cancer care, and often can accurately identify and report symptoms and physical function of the patients they care for. We assessed whether such reporting by caregivers is predictive of adverse patient outcomes. Methods: In this prospective study, adult solid cancer patients on active intravenous systemic therapies and their informal caregivers were recruited from 18 Kaiser Permanente Northern California cancer centers. Using a study mobile app (TOGETHERCare), caregivers completed weekly surveys for 4 weeks, which were based on normalized NIH-PROMIS scores to report patients’ physical function and PRO-CTCAE to report patients’ symptoms. Patients’ adverse clinical outcomes were abstracted from the medical record and included: emergency department (ED) visits or hospitalizations, grade 3-4 adverse events (AEs), and treatment delays, up to 1 month following the 4-week study period, as well as mortality and hospice referrals up to 6 months following the study period. Simple univariate logistic regressions were used to correlate caregiver reports (either at baseline or most proximal preceding an adverse outcome) with mortality and hospice referrals, and quasi-Poisson regressions were used for the other adverse outcome measures. Results: Fifty-four patient-caregiver dyads were enrolled, and 52 were included in this analysis. A third of patients had breast cancer and almost 75% had stage 3 or 4 disease. Caregivers predominantly identified as male (61.5%), spouse/partner (76.9%), and non-Hispanic White (63.5%). At least one adverse outcome was experienced by 36.5% of the patients. Caregiver-reported PRO-CTCAE consistently predicted ED/hospitalizations and mortality, and caregiver-reported PROMIS scores predicted hospice referrals (see Table). Conclusions: The results suggest that caregiver reporting of patients’ symptoms and physical function could help provide early predictions of adverse patient outcomes.[Table: see text]

Contemporary real-world associations between performance status and clinical outcomes in patients with cancer: A retrospective cohort study.

6578 Background: The ECOG-PS (Eastern Cooperative Oncology Group Performance Status) scale is often used to guide cancer care, but the degree to which it predicts contemporary real-world clinical outcomes, in general and within certain patient groups, is relatively unknown. This retrospective cohort study examined associations between ECOG-PS levels and adverse outcomes in cancer patients with diverse patient characteristics. Methods: Various patient characteristics and nurse-rated ECOG-PS scores (range: 0-4) were recorded for all 21,730 adult patients with cancer receiving intravenous systemic therapy between 01/01/2017 and 12/31/2019 at 18 Kaiser Permanente Northern California cancer centers. Differences in baseline characteristics by ECOG-PS scores were evaluated using chi-square tests for categorical variables and ANOVA for continuous variables. Univariable and multivariable Cox Proportional Hazard models were used to test the ability of ECOG-PS to predict the occurrence of adverse clinical outcomes, including 1-month emergency department (ED) visits and hospitalizations, and 6-month mortality. Results: Overall, 42.5% of patients had ECOG-PS = 0, 42.5% had ECOG-PS = 1, 10.5% had ECOG-PS = 2, 4% had ECOG-PS = 3 and 0.4% had ECOG-PS = 4. Most patients were women (58%), non-Hispanic White (61%), English speakers (93%) and married/domestic partners (63%). African Americans, men, older patients, and those with higher Charlson comorbidity index or Stage IV cancer were found to have higher ECOG-PS levels (all p < 0.001). In multivariable analysis, ECOG-PS of 3-4 were associated with higher ED visits (HR 3.85, 95% CI [3.47-4.26]), hospitalizations (HR 4.7, [4.12-5.36]) and mortality (HR 7.34, [6.64-8.11]), compared with ECOG-PS = 0. Upper gastrointestinal (GI) and Stage IV cancers were associated with a higher risk of ED (upper GI: HR 2.39, [2.12-2.68], (stage IV: HR 1.31, [1.21-1.42]), hospitalization (HR 2.67, [2.27-3.13], (HR 1.51, [1.35-1.68]), and mortality rates (HR 3.37, [2.97-3.81], (HR 1.82, [1.68-1.98]), compared to Breast and Stage I cancers; however, advanced age was not associated with these outcomes. Interactions between ECOG-PS and cancer type as well as ECOG-PS and age group were statistically significant (p < 0.001), such that ECOG-PS was more predictive of adverse outcomes in younger patients and those with breast cancer. Conclusions: In this contemporary real-world cohort, multivariable analysis showed that ECOG-PS, cancer type and stage were strong predictors of ED visits, hospitalizations and mortality; however, advanced age was not. These results also show that ECOG-PS is more predictive of clinical outcomes in certain patient groups. Our findings may have implications on the use of ECOG-PS for clinical decision making.

Risk Factors Including Age, Stage and Anatomic Location that Impact the Outcomes of Patients with Synovial Sarcoma.

Synovial sarcoma is a high-grade soft tissue sarcoma that inflicts mostly children and young adults with high mortality rate; however, the risk factors that impact the outcomes remain incompletely understood. We have identified the synovial sarcoma cases from the Kaiser Permanente Northern California cancer registry between 1981 and 2014. Kaplan–Meier plots were used to display disease-free survival (DFS) and overall survival (OS); log-rank tests and Cox proportional hazard models were used to determine the impact of clinical factors on DFS, OS, and disease-specific survival. Tumor size > 5.0 cm and age > 50 years were associated with higher risk of presenting with stage IV disease. Median OS for patients with stage IV was 1.3 years and 7.8 years for early-stage disease. For patients with early-stage disease, tumor size > 5.0 cm was significantly associated with worse DFS, sarcoma-specific morality, and OS. Compared to extremity primary, patients with head and neck and trunk primary had approximately three-fold higher sarcoma-specific mortality and lower OS. There was no significant difference in DFS or OS among three histologic subtypes. Pre-operative and/or post-operative chemotherapy was not associated with improvement in DFS or OS. Twenty-six patients relapsed with predominantly lung metastasis, thirteen of whom received metastatectomy with a median OS of 7.8 years, compared to 2.3 years for patients who did not receive metastatectomy. In conclusion, age older than 50 years and tumor size > 5.0 cm are risk factors for presenting with stage IV disease. For early-stage patients, trunk and head and neck primary as well as tumor size > 5.0 cm are risk factors for decreased OS.

Adjusting for Patient Demographics Has Minimal Effects on Rates of Adenoma Detection in a Large, Community-based Setting

Reliable estimates of adenoma detection rates (ADRs) are needed to inform colonoscopy quality standards, yet little is known about the contributions of patient demographics to variation in ADRs. We evaluated the effects of adjusting for patient age, race/ethnicity, and family history of colorectal cancer on variations in ADRs and the relative rank order of physicians. In a retrospective cohort study, we collected data from Kaiser Permanente Northern California members who were ≥ 50 years old who received colonoscopies from 2006 through 2008. We evaluated ADRs (before and after adjustment for age, sex, race/ethnicity, and family history of colorectal cancer) for 102 endoscopists who performed 108,662 total colonoscopies and 20,792 screening colonoscopies. Adenomas were identified from the pathology database, and cancers were detected by using the Kaiser Permanente Northern California cancer registry. About two-thirds of examiners had unadjusted ADRs for screening exams that met gastroenterology society guidelines (>25% for men and >15% for women), although rates of detection varied widely (7.7%-61.5% for male patients and 1.7%-45.6% for female patients). Adjusting for case mix reduced the variation in detection rates (from 8-fold to 3-fold for male patients and from 27-fold to 5-fold for female patients), but the median change in physician order by detection rate was just 2 ranks, and few physicians changed quartiles of detection. For example, only 3 of 102 endoscopists moved into and 3 out of the lowest quartile of ADR. In a community-based setting, most endoscopists met the ADR standards, although there was wide variation in ADRs, which was similar to that reported from academic and referral settings. Case-mix adjustment reduced variability but had only small effects on differences in ADRs between physicians, and only a small percentage of physicians changed quartiles of detection. Adjustments to ADRs are therefore likely only needed in settings in which physicians have very different patient demographics, such as in sex or age. Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection.

Impact of age on clinicopathological features and survival of patients with noncardia gastric adenocarcinoma.

PurposeGastric cancer often occurs in the elderly but is uncommon in young individuals. Whether young patients have different clinical behaviors and outcomes from those of older patients remain unclear.Materials and MethodsWe identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010. We then compared the clinicopathological features and survival among the different age groups.ResultsThe male : female ratio differed significantly between the younger and older patient groups (0.84 in age <50 years vs. 1.52>60 years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs. 19% patients ≥70 years, P<0.0001), while more older patients were Caucasian (49% patients ≥70 years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed histological type was more prevalent in younger patients (70% patients <40 years vs. 27% patients ≥70 years; P<0.0001), whereas the intestinal type was more frequent in older patients (71% in patients ≥70 years vs. 30% in patients <40 years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the younger patients (80% in patients <40 years vs. 60% in patients ≥70 years; P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing age (overall P=0.0002).ConclusionsYoung patients with gastric cancer had more aggressive disease but higher overall survival rates than older patients. Younger Hispanic patients and older Caucasian patients were more likely to be diagnosed with gastric cancer. These differences may be due to biological predisposition and/or environmental exposure.

Clinical outcome of 1,968 cases of meningiomas from Kaiser Permanente Northern California.

2062 Background: Meningioma is the most common primary brain tumor in the United States, but there is limited data on clinical outcomes. Methods: We performed descriptive and survival analysis of meningioma cases diagnosed 2001-2010 from the Kaiser Permanente Northern California Cancer Registry, which began inclusion of benign brain tumors in 2001. Datasets provided variables on gender, age at diagnosis, race, and vital status. Chart review extracted additional information on mortality, histology, imaging, tumor size, tumor site, and treatment. We used Kaplan Meier method to calculate overall survival (OS) and disease-free survival (DFS) and log-rank test to compare survival rates by variables. Cox proportional hazard models were used to analyze variables relative to endpoints. Results: 1968 cases in 1792 patients with meningioma were analyzed. 55% of cases had histological confirmation. 5- and 10-year OS and DFS for all groups were 76% &amp; 61% and 89% &amp; 82%. Disease progression and recurrence presented in 10% of cases at 10 years, resulting in 4% disease-specific mortality (DSM). Statistically significant prognostic factors of worse DFS were age &gt;= 80, WHO grade 2-3, tumor size &gt;= 18 mm, peritumoral edema on imaging, Simpson grades (SG) 4 or 5, and no surgery. Factors associated with significantly worse OS included age &gt;= 60, male gender, tumor size &gt;= 42 mm, peritumoral edema, SG 4 or 5, no histology and no treatment (NT). SG 1-3 groups provided statistically the highest OS and DFS. There was no significant difference in DFS or OS for definitive RT versus surgery and adjuvant RT groups. Definitive RT showed significantly better OS than NT (HR=0.46, 95% CI: 0.21-0.98). Cases with progression or recurrence had 51% DSM with 65% of deaths associated with lack of salvage therapy. Salvage RT provided better OS benefit compared to other salvage groups (HR=0.35, 95% CI: 0.14-0.91). Conclusions: We demonstrated favorable long-term outcome for meningiomas and confirmed the prognostic benefit of Simpson grading. We have identified additional adverse factors affecting outcome. While surgery remains standard, definitive RT demonstrates comparable outcome to cases not amenable to gross total resection. Salvage RT is effective, providing a survival benefit.

Antioxidant supplement use after diagnosis and breast cancer outcomes.

1539 Background: There is concern that antioxidant supplement use may decrease pro-oxidant effects of chemotherapy and radiation therapy, yet effects on recurrence and survival are largely unknown. The association of post-diagnosis antioxidant use with breast cancer (BC) recurrence and mortality was examined in the Life After Cancer Epidemiology (LACE) Study. Methods: The LACE cohort (n=2,264) consists of women identified primarily through the Kaiser Permanente Northern California Cancer Registry and diagnosed with early stage primary BC from 1997 to 2000; women enrolled approximately two years post-diagnosis. A mailed baseline questionnaire collected data on frequency of antioxidant supplement use since diagnosis (multivitamins +/- minerals, combination multiple carotenoids, beta-carotene, lycopene, vitamin C, vitamin E, selenium, zinc, coenzyme Q10, soy), and other risk factors. BC outcomes were ascertained yearly by mailed questionnaire and confirmed by chart review. Delayed entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Antioxidant supplement use after diagnosis was reported by 81% of women; 71% used multivitamins, 40% used vitamin C, 48% used vitamin E, and 7% used combination multiple carotenoids. Among antioxidant users, frequent use of vitamin C and vitamin E were associated with decreased risk of breast cancer recurrence (HR = 0.73, 95% CI: 0.55-0.97; HR = 0.77, 95% CI: 0.54-0.94, respectively); use of vitamin E was also associated with decreased risk of all-cause mortality (HR = 0.76, 95% CI: 0.58-1.00). Conversely, frequent use of combination multiple carotenoids was associated with increased risk of death from breast cancer (HR = 2.07; 95% CI: 1.21-3.56) and all causes (HR = 1.75; 95% CI: 1.13-2.71), but no such relationship was seen with either beta-carotene or lycopene alone. Conclusions: Frequent use of vitamin C and vitamin E in the period following breast cancer diagnosis was associated with decreased likelihood of recurrence. Frequent use of combination multiple carotenoids during this same period was associated with decreased survival. Effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.

Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study

Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I ≥ 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry (83%). Multivitamin use pre-diagnosis and post-diagnosis was assessed via mailed questionnaire. Outcomes were ascertained yearly by self-report and verified by medical record review. Delayed-entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sociodemographic, tumor, and lifestyle factors. Overall, 54 and 72% of the cohort reported using multivitamins pre- and post-diagnosis, respectively. A total of 380 recurrences, 212 breast cancer deaths, and 396 total deaths were confirmed. Compared to never use, multivitamin use after diagnosis was not associated with any outcome (recurrence HR = 0.92; 95% CI: 0.71, 1.20; total mortality HR = 0.92; 95% CI: 0.71, 1.19). Compared to never use, persistent use of multivitamins from pre- to post-diagnosis was associated with a non-significant decreased risk of recurrence (HR = 0.76; 95% CI: 0.54, 1.06) and total mortality (HR = 0.79; 95% CI: 0.56, 1.12). The protective associations were limited to women who had been treated by radiation only (P for trend = 0.048 and 0.083 for recurrence and total mortality, respectively) and both radiation and chemotherapy (P for trend = 0.015 and 0.095 for recurrence and total mortality, respectively). In stratified analyses, women who consistently used multivitamins before and after diagnosis and ate more fruits/vegetables (P for trend = 0.008) and were more physically active (P for trend = 0.034) had better overall survival. Multivitamin use along with practice of other health-promoting behaviors may be beneficial in improving breast cancer outcomes in select groups of survivors.

Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort

There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer-related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta blockers (BBs) and/or angiotensin-converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, P=0.04), but not cause-specific or overall mortality. Combined ACEi and BB were associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, P=0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes.

Alcohol Consumption and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer: The Life After Cancer Epidemiology Study

To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors. Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors. Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking ≥ 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non-breast cancer death. Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non-breast cancer death were suggested.

Alcohol Consumption and Breast Cancer Recurrence and Survival among Women with Early-Stage Breast Cancer.

Abstract Purpose: To describe alcohol consumption and examine its association with breast cancer recurrence and mortality in the Life After Cancer Epidemiology (LACE) study, a prospective cohort study of early-stage breast cancer survivors.Methods: Patients included 1897 participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (beer, wine, and liquor) was assessed at cohort entry using a food frequency questionnaire. A total of 349 breast cancer recurrences and 332 overall deaths were ascertained after an average follow-up of 5.93 years. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.Results: A total of 958 women (51%) were considered drinkers (&amp;gt;0.5 g of alcohol per day), and the majority drank wine (90%), followed by liquor (43%), and beer (36%). Drinking ≥6 g/day of alcohol compared to minimal or no drinking (≤0.5 g/day) was associated with an increased risk of breast cancer recurrence (HR = 1.34; 95% CI: 1.00, 1.82) and death (HR = 1.51; 95% CI: 1.00, 2.28). The increased risk of recurrence appeared to be greater among postmenopausal (P for trend = .03) and overweight or obese women (P for trend = .03). No associations were observed for risk of overall mortality and alcohol use.Conclusions: Consuming 3 to 4 alcoholic drinks or more per week might be related to an increased risk of breast cancer recurrence, particularly among postmenopausal and heavier women, regardless of other prognostic factors. While additional prospective studies are needed, these observations suggest that after a breast cancer diagnosis, women should consider limiting their consumption of alcohol. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 17.

The epidemiology of herpes zoster in patients with invasive cancer

9562 Background: Given the limited available data, the aim of this study was to estimate the incidence of Herpes Zoster (HZ) in cancer patients. Methods: In this retrospective cohort study, we used the Kaiser Permanente Northern California cancer registry to identify adult health plan members diagnosed with an invasive hematologic malignancy (HM) or solid tumor malignancy (STM) during 2001–2005. Potential episodes of HZ were ascertained from time of cancer diagnosis through 2006 from electronic databases using inpatient and outpatient diagnoses, laboratory tests, and prescriptions for antivirals. HZ diagnoses were confirmed by abstraction and clinical review of information from patients' inpatient and outpatient medical records. Incidence rates were calculated as the number of new occurrences of HZ per person-time of follow-up. Age-standardized incidence ratios (SIRs) were computed to compare HZ rates in cancer patients to reported rates in the general population (Yawn et al, 2007). Results: Among the 4,728 STM patients (mean age 66 years, range 18–102), the rate of HZ was 12/1000 person years (py) of follow-up (total 9170 py). Among the 1504 HM patients (mean age 67 years, range 18–97), the rate of HZ was 33/1000 py (total 2355 py). The SIRs and 95% confidence intervals for STM and HM were 1.7 (1.4–2.1) and 4.5 (3.5–5.6), respectively. Among patients with HM, incidence rates were highest in the first year after cancer diagnosis (40/1000 py); rates did not appear to vary markedly over time among patients with STM. For either cancer type, HZ rates were similar for males and females and did not increase consistently with increasing age. Conclusions: Compared to the general population, the incidence of HZ was nearly 2 times higher in patients with STM and over 4 times higher in patients with HM. HZ rates did not differ markedly by age or gender. [Table: see text]

Dietary Patterns and Breast Cancer Recurrence and Survival Among Women With Early-Stage Breast Cancer

To determine the association of dietary patterns with cancer recurrence and mortality of early-stage breast cancer survivors. Patients included 1,901 Life After Cancer Epidemiology Study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Diet was assessed at cohort entry using a food frequency questionnaire. Two dietary patterns were identified: prudent (high intakes of fruits, vegetables, whole grains, and poultry) and Western (high intakes of red and processed meats and refined grains). Two hundred sixty-eight breast cancer recurrences and 226 all-cause deaths (128 attributable to breast cancer) were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Increasing adherence to a prudent dietary pattern was associated with a statistically significant decreasing risk of overall death (P trend = .02; HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90) and death from non-breast cancer causes (P trend = .003; HR for highest quartile = 0.35; 95% CI, 0.17 to 0.73). In contrast, increasing consumption of a Western dietary pattern was related to an increasing risk of overall death (P trend = .05) and death from non-breast cancer causes (P = .02). Neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer. These observations were generally not modified by physical activity, being overweight, or smoking. Women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.

Menopausal Hormone Therapy and Breast Cancer Phenotype: Does Dose Matter?

Duration and type of menopausal hormone therapy (HT) has been associated with increased breast cancer risk and the development of estrogen receptor (ER)-positive tumors. The effect of HT dose on breast cancer tumor characteristics remains undefined. We sought to determine if HT dosing regimens influence breast cancer phenotype. We conducted a retrospective review of incident female breast cancers occurring in the year 2003 listed in the Kaiser Permanente Northern California Cancer Registry. Type of HT, dose, number of tablets dispensed, tumor phenotype, stage, grade, and histology were obtained from electronic records for women aged >/=50 years who had more than 1 year of uninterrupted pharmacy data (n = 1701). A dose index of HT exposure was created and odds ratios were used to determine if tumor phenotype varied between exposure groups. These results were compared with a previously published analysis of HT duration on tumor phenotype conducted with the same dataset. The cumulative effect of estrogen and progesterone hormone therapy as calculated by factoring both dose and duration of HT use prior to breast cancer diagnosis did not reveal any new associations that were not previously identified by analysis of HT duration of exposure alone. Low-dose-index combination-HT users were less likely to have tumors with an ER-positive phenotype. An overall trend developed in which low- and high-dose-index exposed women had the lowest rates of ER- and progesterone receptor (PR) -positive tumors. Duration of use is an adequate surrogate for determining overall exposure to HT when considering the effect of HT on breast cancer phenotype.

Estrogen Receptor–Negative Breast Cancer Is Less Likely to Arise among Lipophilic Statin Users

Preclinical studies have shown the anticancer potential of HMG-CoA reductase enzyme inhibitors (statins), whereas epidemiologic studies remain controversial. Because lipophilic statins show preclinical anticancer activity against hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)]-negative breast cancer models, we explored the hormone receptor phenotype of breast cancers that arise in statin users. We did a retrospective cohort analysis via electronic pharmacy records from the Kaiser Permanente Northern California Cancer Registry on 2,141 female patients listed in 2003 as incident cases of breast malignancy. Measures included tumor grade, stage, and receptor phenotype in statin users versus nonusers and controlled for hormone replacement therapy and race. 387 of the 2,141 breast cancer patients used lipophilic statins [lovastatin (85%), simvastatin, and atorvastatin]. Fifty-one women developed ER/PR-negative tumors. The age-adjusted odds ratio (OR) of developing an ER/PR negative tumor was 0.63 (95% confidence interval, 0.43-0.92; P = 0.02) for statin use >or=1 year before breast cancer diagnosis compared with statin use <1 year (including nonuse). Breast cancers in patients with >or=1 year of statin use were more likely to be low grade (OR, 1.44) and less invasive stage (OR, 1.42). Breast cancer patients with exposure to statins have proportionately fewer ER/PR-negative tumors that are of lower grade and stage. Although our data set cannot address whether statins affect the incidence of breast cancer, we show that statin use may influence the phenotype of tumors. This suggests a new potential strategy for breast cancer prevention, that of combining statins with agents that prevent ER-positive cancer (tamoxifen, aromatase inhibitors).

Type and Duration of Exogenous Hormone Use Affects Breast Cancer Histology

It is unclear whether hormone replacement therapy (HRT), in addition to increasing risk for breast cancer, affects the type of breast cancer diagnosed. We conducted this investigation to assess whether the type of hormone used (none, estrogen, progesterone, or combined) and duration of use influences subsequent breast cancer histology. We performed a retrospective cohort analysis among women listed as incident cases of breast malignancy in the Kaiser Permanente Northern California Cancer Registry during 2003 (n = 2830). Type and duration of hormone used (none, estrogen, progesterone, or combined) before breast cancer diagnosis was obtained from electronic pharmacy records. The association between type and duration of hormone use with characteristics of subsequent breast cancers was examined. Among women aged >50 years (n = 1701), any use of estrogen, progesterone, or combination therapy was not associated with an increased risk of estrogen receptor (ER)-positive disease. However, >6 months' use of combined HRT increased the odds of ER-positive tumors (odds ratio, 1.65; 95% confidence interval, 1.07-2.5; P = .02). Estrogen HRT patients were more likely than nonusers to present with low-grade (P = .05), and early-stage tumors (P = .03). This trend was not seen in combined HRT users. Short-duration HRT did not increase the likelihood of ER-positive breast cancer. However, prolonged duration of combined HRT, but not estrogen or progesterone alone, resulted in a marked increase in ER-positive disease. Our findings suggest that the effect of combined HRT on breast cancer incidence or progression is not immediate and that long-term use is more likely to affect breast cancer histology.

Life After Cancer Epidemiology (LACE) Study: A cohort of early stage breast cancer survivors (United States)

The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage breast cancer survivors, was established in 2000 to examine how modifiable behavioral risk factors affect quality of life and long-term survival. Women were recruited primarily from the Kaiser Permanente Northern California Cancer Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline data were collected, on average, at two years post-diagnosis through self-administered questionnaires that included information on demographics, medical history, anthropometry, diet, supplements, physical activity and quality of life. The purpose of this paper is to describe the creation and baseline characteristics of the cohort. Forty-six percent of women to whom questionnaires were mailed agreed to participate. The cohort which is 80% white, was diagnosed predominantly with Stage I and II breast cancer (93%), and will have been followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women reported slightly over four daily servings of fruit and vegetables, well below the suggested 5-A-Day national guidelines. Compared to women free of cancer, physical activity patterns were similar, while weight gain, especially in younger women, was higher than is typical. These data suggest that in the early years post-diagnosis, breast cancer survivors exhibit similar patterns to the general population in many health behaviors.