Faculty Bibliography

BACKGROUND: The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied. STUDY DESIGN: In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990-1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence. RESULTS: Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio = 0.32; 95% CI, 0.22-0.47), and women at moderate risk were about half as likely (odds ratio = 0.54; 95% CI, 0.35-0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio = 5.1; 95% CI, 1.9-13.5) and low risk (hazard ratio = 3.2; 95% CI, 1.1-8.9). The association among women at high risk was weak (hazard ratio = 1.3; 95% CI, 0.75-2.1). CONCLUSIONS: Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence

Analysis of observational cohort data is subject to bias from unobservable risk selection. The authors compared econometric models and treatment effectiveness estimates using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims data for women diagnosed with ductal carcinoma in situ. Treatment effectiveness estimates for mastectomy and breast-conserving surgery (BCS) with or without radiotherapy were compared using three different models: simultaneous-equations model, discrete-time survival model with unobserved heterogeneity (frailty), and proportional hazards model. Overall trends in disease-free survival (DFS), or time to first subsequent breast event, by treatment are similar regardless of the model, with mastectomy yielding the highest DFS over 8 years of follow-up, followed by BCS with radiotherapy, and then BCS alone. Absolute rates and direction of bias varied substantially by treatment strategy. DFS was underestimated by single-equation and frailty models compared with the simultaneous-equations model and randomized controlled trial results for BCS with radiotherapy and overestimated for BCS alone

BACKGROUND: The high incidence of ductal carcinoma in situ (DCIS) and variations in its treatment motivate inquiry into the comparative effectiveness of treatment options. Few such comparative effectiveness studies of DCIS, however, have been performed with detailed information on clinical and treatment attributes. METHODS: We collected detailed clinical, nonclinical, pathological, treatment, and long-term outcomes data from multiple medical records of 994 women who were diagnosed with DCIS from 1985 through 2000 in Monroe County (New York) and the Henry Ford Health System (Detroit, MI). We used ipsilateral disease-free survival models to characterize the role of treatments (surgery and radiation therapy) and margin status (positive, close [<2 mm], or negative [>/=2 mm]) and logistic regression models to characterize the determinants of treatments and margin status, including the role of surgeons. All statistical tests were two-sided. RESULTS: Treatments and margin status were statistically significant and strong predictors of long-term disease-free survival, but results varied substantially by surgeon. This variation by surgeon accounted for 15%-35% of subsequent ipsilateral 5-year recurrence rates and for 13%-30% of 10-year recurrence rates. The overall differences in predicted 5-year disease-free survival rates for mastectomy (0.993), breast-conserving surgery with radiation therapy (0.945), and breast-conserving surgery without radiation therapy (0.824) were statistically significant (P(diff) < .001 for each of the differences). Similarly, each of the differences at 10 years was statistically significant (P < .001). CONCLUSIONS: Our work demonstrates the contributions of treatments and margin status to long-term ipsilateral disease-free survival and the link between surgeons and these key measures of care. Although variation by surgeon could be generated by patients' preferences, the extent of variation and its contribution to long-term health outcomes are troubling. Further work is required to determine why women with positive margins receive no additional treatment and why margin status and receipt of radiation therapy vary by surgeon

OBJECTIVE: To identify factors associated with delayed radiotherapy (RT) in older women with early-stage breast cancer. METHODS: We studied 541 women age >or=65 years diagnosed with early-stage breast cancer in 1990-1994 at 5 integrated healthcare delivery systems and treated with breast-conserving surgery and RT, but not chemotherapy. We examined whether demographic, tumor, or treatment characteristics were associated with RT delays of >8 weeks postsurgery using chi(2) tests and multivariable logistic regression. RESULTS: Seventy-six women (14%) had delayed RT, with a median delay of 14 weeks. Even though they had insurance and access to care, nonwhite and Hispanic women were much more likely than white women to have delayed RT (odds ratio = 3.3; 95% confidence interval = 1.7, 10) in multivariable analyses that controlled for demographic and clinical variables. CONCLUSIONS: Timely RT should be facilitated through physician and patient education, navigation, and notification programs to improve quality of care. Queues for RT appointments should be evaluated on an ongoing basis to ensure adequate access. Future research should examine modifiable barriers to RT timeliness and whether delays impact long-term outcomes

PURPOSE: Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. PATIENTS AND METHODS: A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). RESULTS: Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. CONCLUSION: Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence

BACKGROUND: The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer. METHODS: A decision-analytic model from the Medicare payer perspective followed hypothetical patients who were treated with combined 5-fluorouracil, leucovorin, and irinotecan. Under usual care, patients received a full dose of irinotecan. With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele. Test performance, chemotherapy toxicity, and quality-of-life weights were derived from clinical literature and product labels, and costs were derived from 2007 Medicare fee schedules. Chemotherapy efficacy after dose reduction, adverse event risk, and other parameters were varied in 1-way and probabilistic sensitivity analyses. The authors also calculated the value of investing in further studies of chemotherapy efficacy after homozygote dose reductions. RESULTS: Pretreatment genetic testing costs less ($272 savings per patient tested) and yields slightly improved quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested; approximately 2 quality-adjusted hours). Results depended on treatment efficacy but not adverse event risk assumptions. The results indicated that testing would avoid 84 cases of severe neutropenia, including 4.4 deaths. At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be > or =98.4% of full-dose efficacy for genetic testing to remain preferred. Future studies to determine whether this efficacy level can be achieved have an economic value of $22 million. CONCLUSIONS: The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy. Future studies to evaluate reduced-dose efficacy in homozygotes should be considered

BACKGROUND: As information is disseminated about best practices, variations in patterns of care should diminish over time. OBJECTIVE: To test the hypotheses that differences in rates of a surgical procedure are associated with type of insurance in an era of evolving practice guidelines and that insurance and site differences diminish with time as consensus guidelines disseminate among the medical community. METHODS: We use lymph node dissection among women with ductal carcinoma in situ (DCIS) as an example of a procedure with uncertain benefit. Using a sample of 1051 women diagnosed from 1985 through 2000 at 2 geographic sites, we collected detailed demographic, clinical, pathologic, and treatment information through abstraction of multiple medical records. We specified multivariate logistic models with flexible functions of time and time interactions with insurance and treatment site to test hypotheses. RESULTS: Lymph node dissection rates varied significantly according to site of treatment and insurance status after controlling for clinical, pathologic, treatment, and demographic characteristics. Rates of lymph node dissection decreased over time, and differences in lymph node dissection rates according to site and generosity of insurance were no longer significant by the end of the study period. CONCLUSIONS: We have demonstrated that rates of a discretionary surgical procedure differ according to nonclinical factors, such as treatment site and type of insurance, and that such unwarranted variation decreases over time with diminishing uncertainty and in an era of diffusion of clinical guidelines

OBJECTIVES: To examine the effect of socioeconomic factors on survival in black and white patients with local or regional prostate cancer. METHODS: All cases (n = 2046) of clinically localized prostate cancer diagnosed from 1990 to 2000 at the Henry Ford Health System and the Henry Ford Medical Group, equal access health centers, were included. Data on the stage, grade, age at diagnosis, socioeconomic status, treatment given, comorbidities, and vital statistics were gathered from the Henry Ford Medical Group tumor registry and computerized databases, pathologic reports, patient charts, Surveillance, Epidemiology, and End Results database, and the national death registry. The endpoints were the overall and cancer-specific survival. Survival was calculated using Cox proportional hazards regression models. RESULTS: Of the 2046 cases, 1243 were white and 803 were black. Black patients were more likely to have lower incomes, a greater baseline prostate-specific antigen level, and greater comorbidities. They were also more likely to undergo radiotherapy and less likely to undergo radical prostatectomy. Univariate analysis, with white race as the baseline hazard, showed that black patients had significantly increased cancer-specific (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.01-2.13) and overall (HR 1.29, 95% CI 1.09-1.53) mortality. However, adjusting for insurance status and income on multivariate analysis revealed no significant differences in cancer-specific (HR 1.04, 95% CI 0.66-1.64) and overall (HR 0.96, 95% CI 0.78-1.18) survival. CONCLUSIONS: In this cohort, socioeconomic factors were sufficient to explain the disparity in survival between white and black patients. Survival differences disappeared after adjusting for income status on multivariate analysis

BACKGROUND: The study aimed to identify factors associated with less-than-optimal radiotherapy (RT) and its impact on disease-free survival in women aged 66+ years diagnosed with stage I breast cancer or ductal carcinoma in situ (DCIS). METHODS: The subjects were women diagnosed from 1991 to 1999 in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database who underwent breast-conserving surgery and RT within 12 months postdiagnosis. The authors conducted descriptive and multivariate survival analyses, and considered age, race, poverty, marital status, comorbidity indices, rural/urban, radiation oncologist density, comedo necrosis histology (DCIS only), chemotherapy receipt (stage I only), and RT completion (3+ weeks of treatment) and delay (8+ weeks postsurgery without chemotherapy; 4+ weeks postchemotherapy). RESULTS: Of 7791 subjects, 16% experienced RT delay, and 3% had incomplete RT. Subjects with stage I disease who were more likely to delay RT were of black race (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.17-2.08), whereas women in areas of high radiation oncologist density were less likely to delay (OR, 0.73; 95% CI, 0.66-0.81). Those living in high poverty areas were less likely to complete RT (P < .03), as were those undergoing chemotherapy (OR, 1.82; 95% CI, 1.15-2.88). Stage I breast cancer patients with delayed RT were more likely to experience a subsequent breast event (OR, 1.14; 95% CI, 1.00-1.30), and those with incomplete RT had a higher rate of overall mortality (OR, 1.32; 95% CI, 1.06-1.63). Factors associated with lower subsequent breast events included older age, lower poverty, and being married. RT delays of 12+ weeks (or 8+ weeks postchemotherapy) had a strongly negative impact on subsequent events (OR, 3.94; 95% CI, 2.51-6.17 for DCIS; OR, 2.77; 95% CI, 1.84-2.59 for stage I). CONCLUSIONS: RT should be facilitated to ensure completion and timeliness, especially for early invasive breast cancer patients