Diana S. M. Buist

Quality of life of 5-10 year breast cancer survivors diagnosed between age 40 and 49.

BackgroundThe purpose of this report is to examine the correlates of quality of life (QOL) of a well-defined group of long-term breast cancer survivors diagnosed between the ages of 40 and 49.MethodsWomen were eligible if they were diagnosed with invasive breast cancer or ductal carcinoma in situ 5 to 10 years before June 30, 1998 and were enrolled at Group Health Cooperative, a health maintenance organization in western Washington State. A questionnaire was mailed to 290 women; 216 were included in this analysis. The questionnaire included standardized measures of QOL [e.g., the Cancer Rehabilitation Evaluation System (CARES-SF) and SF-36] as well as general demographic and medical information. ANOVA and logistic regression were used to estimate correlates of self-reported QOL.ResultsThe mean age at diagnosis was 44.4 years, and the average time since diagnosis was 7.3 years. Women reported high levels of functioning across several standardized QOL scales; mild impairment was found on the CARES-SF Sexual Scale. The presence of breast-related symptoms at survey, use of adjuvant therapy, having lower income, and type of breast surgery were significantly associated with lower QOL 5 to 10 years post-diagnosis on one or more of the scales.ConclusionsOur results emphasize that younger long-term survivors of breast cancer have a high QOL across several standardized measures. However, the long-term consequences of adjuvant therapy and the management of long-term breast-related symptoms are two areas that may be important for clinicians and women with breast cancer in understanding and optimizing long-term QOL.

Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years: a comparative modeling study of risk.

BACKGROUNDnTiming of initiation of screening for breast cancer is controversial in the United States.nnnOBJECTIVEnTo determine the threshold relative risk (RR) at which the harm-benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years.nnnDESIGNnComparative modeling study.nnnDATA SOURCESnSurveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.nnnTARGET POPULATIONnA contemporary cohort of women eligible for routine screening.nnnTIME HORIZONnLifetime.nnnPERSPECTIVEnSocietal.nnnINTERVENTIONnMammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).nnnOUTCOME MEASURESnnnnBENEFITSnlife-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm-benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted.nnnRESULTS OF BASE-CASE ANALYSISnScreening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm-benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate.nnnRESULTS OF SENSITIVITY ANALYSISnThe threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions.nnnLIMITATIONnRisk was assumed to influence onset of disease without influencing screening performance.nnnCONCLUSIONnWomen aged 40 to 49 years with a 2-fold increased risk have similar harm-benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm-benefit ratios vary by screening method, interval, and outcome measure.nnnPRIMARY FUNDING SOURCEnNational Cancer Institute.

Association between Mammographic Breast Density and Breast Cancer Tumor Characteristics

Objective: Few studies have examined the association between breast density and breast cancer tumor characteristics. We examined the association between hormonal, proliferative, and histologic tumor characteristics and mammographic breast density in women with breast cancer. Methods: We conducted a cross-sectional analysis in 546 women diagnosed with invasive breast cancer to evaluate the associations between breast density and tumor size, lymph node status, lymphatic or vascular invasion, histologic grade, nuclear grade, tumor differentiation, mitotic index, tumor necrosis, Ki-67 proliferation, estrogen receptor, progesterone receptor, p53, p27, cyclin E, Bcl-2, and C-erb-B2 invasion. Breast density was classified as fatty (Breast Imaging Reporting and Data System code 1 or 2; n = 373) or dense (Breast Imaging Reporting and Data System code 3 or 4; n = 173) for the cancer-free breast. A single pathologist measured all tumor markers. We examined whether the relationships were modified by interval cancer or screen-detected cancer. Results: Women with a tumor size >1.0 cm were more likely to have dense breasts compared with women with a tumor size ≤1.0 cm after adjusting for confounders (odds ratio, 2.0; 95% confidence interval, 1.2-3.4 for tumor sizes 1.1-2.0 cm; odds ratio, 2.3; 95% confidence interval, 1.3-4.4 for tumor sizes 2.1-10 cm). Tumor size, lymph node status, and lymphatic or vascular invasion were positively associated with breast density among screen-detected cancers. Histologic grade and mitotic index were negatively associated with breast density in women diagnosed with an interval cancer. Conclusions: These results suggest that breast density is related to tumor size, lymph node status, and lymphatic or vascular invasion in screen-detected cancers. Additional studies are needed to address whether these associations are due to density masking the detection of some tumors, a biological relationship, or both.

Racial differences in tumor stage and survival for colorectal cancer in an insured population

Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients.

Statin use and breast cancer risk in a large population-based setting.

Background: Mechanistic studies suggest that 3-hydroxy-3-methylglutaryl CoA inhibitors (statins) reduce the risk of breast cancer. Observational studies offer mixed results. Methods: To evaluate the relation between statin use and breast cancer risk, we conducted a cohort study among women ages 45 to 89 years within an integrated health care delivery system. Information on statin use and covariates were obtained from automated databases. We identified breast cancer cases through the Surveillance, Epidemiology, and End Results registry. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for invasive breast cancer among statin users compared with nonusers. Results: Among 92,788 women studied from 1990 to 2004, median follow-up time was 6.4 years, and 2,707 breast cancer cases were identified. During the study period, 7.4% of women used statins for at least 1 year, and the median duration of use was 3.1 years. We found no difference in breast cancer risk among statin users (HR, 1.07; 95% CI, 0.88-1.29) compared with nonusers. Risk of breast cancer did not differ by duration of use (1-2.9, 3-4.9, or ≥5 years) or hydrophobic statin use. We found a suggestive increased risk of breast cancer among statin users of ≥5 years (HR, 1.27; 95% CI, 0.89-1.81 for any statins and HR, 1.47; 95% CI, 0.89-2.44 for hydrophobic statins) and of estrogen receptor–negative tumors with increasing duration of statin use (1-2.9 years: HR, 1.33; 95% CI, 0.64-2.77; 3-4.9 years: HR, 1.68; 95% CI, 0.72-3.92; ≥5 years: HR, 1.81; 95% CI, 0.75-4.36). Conclusion: This study does not support an association between statin use and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(3):416–21)

Evaluating Organized Breast Cancer Screening Implementation The Prevention of Late-Stage Disease?

The objective of our study was to evaluate organized breast cancer screening implementation by measuring the association between screening program enrollment and late-stage disease. Our setting was a health plan using mailed mammography reminders to women ages ≥40. We conducted yearly cross-sectional summaries of mammography experience and late-stage (regional or distant Surveillance Epidemiology and End Results Reporting (SEER) stage) breast cancer occurrence for all of the health-plan women ages ≥40 (1986–1998). We estimated the odds of late-stage breast cancer among health-plan and surrounding community women because it was too early to compare changes in mortality. We also estimated the odds of late-stage disease (1995–1998) associated with program enrollment and mammography screening among health-plan women. We found that mammography-within-two-years increased within the health plan from 25.9% to 51.2% among women ages 40–49 and from 32.9% to 74.7% among women ages ≥50. Health-plan late-stage rates were lower than those in the surrounding community [ages 40–49: odds ratio (OR), 0.87; 95% confidence interval (CI), 0.77–0.99; ages 50–79: OR, 0.86; 95% CI, 0.80–0.92] and declined parallel to the community. Among health-plan cancer cases, women ages ≥43 who were enrolled in the screening program and who had at least one program mammogram were less likely to have late-stage disease compared with the women not enrolled in the program (OR, 0.31; 95% CI, 0.16–0.61) but the odds of late-stage was also reduced among program-enrolled women not receiving program mammograms (OR, 0.45; 95% CI, 0.21–0.95). We concluded that enrollment in organized screening is associated with increased likelihood of mammography and reduced odds of late-stage breast cancer. Addressing the concerns of un-enrolled women and those without mammograms offers an opportunity for further late-stage disease reduction.

Accuracy and Outcomes of Screening Mammography in Women With a Personal History of Early-Stage Breast Cancer

CONTEXTnWomen with a personal history of breast cancer (PHBC) are at risk of developing another breast cancer and are recommended for screening mammography. Few high-quality data exist on screening performance in PHBC women.nnnOBJECTIVEnTo examine the accuracy and outcomes of mammography screening in PHBC women relative to screening of similar women without PHBC.nnnDESIGN AND SETTINGnCohort of PHBC women, mammogram matched to non-PHBC women, screened through facilities (1996-2007) affiliated with the Breast Cancer Surveillance Consortium.nnnPARTICIPANTSnThere were 58,870 screening mammograms in 19,078 women with a history of early-stage (in situ or stage I-II invasive) breast cancer and 58,870 matched (breast density, age group, mammography year, and registry) screening mammograms in 55,315 non-PHBC women.nnnMAIN OUTCOME MEASURESnMammography accuracy based on final assessment, cancer detection rate, interval cancer rate, and stage at diagnosis.nnnRESULTSnWithin 1 year after screening, 655 cancers were observed in PHBC women (499 invasive, 156 in situ) and 342 cancers (285 invasive, 57 in situ) in non-PHBC women. Screening accuracy and outcomes in PHBC relative to non-PHBC women were cancer rates of 10.5 per 1000 screens (95% CI, 9.7-11.3) vs 5.8 per 1000 screens (95% CI, 5.2-6.4), cancer detection rate of 6.8 per 1000 screens (95% CI, 6.2-7.5) vs 4.4 per 1000 screens (95% CI, 3.9-5.0), interval cancer rate of 3.6 per 1000 screens (95% CI, 3.2-4.1) vs 1.4 per 1000 screens (95% CI, 1.1-1.7), sensitivity 65.4% (95% CI, 61.5%-69.0%) vs 76.5% (95% CI, 71.7%-80.7%), specificity 98.3% (95% CI, 98.2%-98.4%) vs 99.0% (95% CI, 98.9%-99.1%), abnormal mammogram results in 2.3% (95% CI, 2.2%-2.5%) vs 1.4% (95% CI, 1.3%-1.5%) (all comparisons P < .001). Screening sensitivity in PHBC women was higher for detection of in situ cancer (78.7%; 95% CI, 71.4%-84.5%) than invasive cancer (61.1%; 95% CI, 56.6%-65.4%), P < .001; lower in the initial 5 years (60.2%; 95% CI, 54.7%-65.5%) than after 5 years from first cancer (70.8%; 95% CI, 65.4%-75.6%), P = .006; and was similar for detection of ipsilateral cancer (66.3%; 95% CI, 60.3%-71.8%) and contralateral cancer (66.1%; 95% CI, 60.9%-70.9%), P = .96. Screen-detected and interval cancers in women with and without PHBC were predominantly early stage.nnnCONCLUSIONnMammography screening in PHBC women detects early-stage second breast cancers but has lower sensitivity and higher interval cancer rate, despite more evaluation and higher underlying cancer rate, relative to that in non-PHBC women.

Reproductive history and risk of three breast cancer subtypes defined by three biomarkers.

Breast cancer subtypes defined by estrogen receptor (ER), progesterone receptor (PR), and HER2 expression are biologically distinct and thus, may have distinct etiologies. In particular, it is plausible that risk factors operating through hormonal mechanisms are differentially related to risk of such tumor subtypes. Using data from the Breast Cancer Surveillance Consortium, we explored associations between reproductive history and three breast cancer subtypes. Data on parity and age at first birth were collected from 743,623 women, 10,896 of whom were subsequently diagnosed with breast cancer. Cases were classified into three subtypes based on tumor maker expression: (1) ER positive (ER+, Nxa0=xa08,203), (2) ER negative/PR negative/HER2 positive (ER−/PR−/HER2+, Nxa0=xa0288), or (3) ER-, PR-, and HER2-negative (triple-negative, Nxa0=xa0645). Associations with reproductive history, evaluated using Cox regression, differed significantly across tumor subtypes. Nulliparity was most strongly associated with risk of ER+ breast cancer [hazard ratio (HR)xa0=xa01.31, 95% confidence interval (CI): 1.23–1.39]; late age at first birth was most strongly associated with risk of ER-/PR-/HER2+ disease (HRxa0=xa01.83, 95% CI: 1.31–2.56). Neither parity nor age at first birth was associated with triple-negative breast cancer. In contrast to ER+ and ER−/PR−/HER2+ subtypes, reproductive history does not appear to be a risk factor for triple-negative breast cancer.

Adverse events after screening and follow-up colonoscopy

ObjectiveWe provide new information about how the risk of adverse events following colonoscopy varies by age and indication (screening vs. follow-up performed to evaluate a positive result from another screening modality).MethodsWe constructed a retrospective cohort comprised of 43,456 individuals aged 40–85xa0years enrolled in a large integrated healthcare organization in Washington State who underwent outpatient colonoscopy between 1994 and 2009. We calculated rates of serious adverse events (perforation, hemorrhage, and acute diverticulitis) in the 30xa0days following colonoscopy and compared rates using log-binomial regression models.ResultsWe observed 4.7 serious adverse events per 1,000 screening colonoscopies and 6.8 per 1,000 follow-up colonoscopies. Polypectomy increased the rate of serious adverse events (relative rate [RR], 2.64; 95% confidence interval [CI], 1.97–3.56). Older age was associated with increased risk of serious adverse events, after adjusting for polypectomy, gender, and indication. Compared to individuals aged 50–64xa0years, risk was elevated for those aged 65–74 (RR, 1.93; 95% CI, 1.40–2.65) and 75–85 (RR, 3.21; 95% CI 2.14–4.86). We observed similar age effects in individuals with and without significant comorbid conditions.ConclusionsThe risks of serious adverse events following colonoscopy performed as part of screening are low but increase with age and are more likely after polypectomy.

Bone mineral density and breast cancer risk in postmenopausal women

Two recent studies have shown a womans bone mineral density (BMD) (a composite measure of exposure to many different factors throughout ones lifetime) predicts breast cancer. In a prospective cohort study, we examined whether hip BMD was associated with breast cancer risk among 8203 postmenopausal women. During an average follow-up of 3.7 years, 131 incident breast cancer cases (102 invasive) were identified. Cox proportional hazards models were used to obtain estimates of the relative risk of breast cancer. Our results demonstrate an increase in breast cancer risk among women with higher BMD. Independent of age, geographic area, and body mass index, relative to the lowest BMD quartile the risk of breast cancer (95% confidence interval) by increasing quartile was 1.9 (1.1, 3.2), 1.5 (0.8, 2.6), and 1.5 (0.8, 2.7), respectively. An examination of other factors important in determining BMD may help explain the positive association between BMD and breast cancer.