Faculty Bibliography

BACKGROUND: Little is known about the cost to Medicare of breast cancer screening or whether regional-level screening expenditures are associated with cancer stage at diagnosis or treatment costs, particularly because newer breast cancer screening technologies, like digital mammography and computer-aided detection (CAD), have diffused into the care of older women. METHODS: Using the linked Surveillance, Epidemiology, and End Results-Medicare database, we identified 137 274 women ages 66 to 100 years who had not had breast cancer and assessed the cost to fee-for-service Medicare of breast cancer screening and workup during 2006 to 2007. For women who developed cancer, we calculated initial treatment cost. We then assessed screening-related cost at the Hospital Referral Region (HRR) level and evaluated the association between regional expenditures and workup test utilization, cancer incidence, and treatment costs. RESULTS: In the United States, the annual costs to fee-for-service Medicare for breast cancer screening-related procedures (comprising screening plus workup) and treatment expenditures were $1.08 billion and $1.36 billion, respectively. For women 75 years or older, annual screening-related expenditures exceeded $410 million. Age-standardized screening-related cost per beneficiary varied more than 2-fold across regions (from $42 to $107 per beneficiary); digital screening mammography and CAD accounted for 65% of the difference in screening-related cost between HRRs in the highest and lowest quartiles of cost. Women residing in HRRs with high screening costs were more likely to be diagnosed as having early-stage cancer (incidence rate ratio, 1.78 [95% CI, 1.40-2.26]). There was no significant difference in the cost of initial cancer treatment per beneficiary between the highest and lowest screening cost HRRs ($151 vs $115; P = .20). CONCLUSIONS: The cost to Medicare of breast cancer screening exceeds $1 billion annually in the fee-for-service program. Regional variation is substantial and driven by the use of newer and more expensive technologies; it is unclear whether higher screening expenditures are achieving better breast cancer outcomes.

Accelerated partial breast radiotherapy (RT) strategies (3-D conformal external-beam RT (3-D CRT) and brachytherapy with balloon catheter) reduce time and transportation burdens of whole breast RT for breast cancer. Long-term clinical trial evidence is unavailable for accelerated modalities, but uncertainty might be acceptable for patients likely to receive suboptimal whole breast RT. The objective of this study is to assess the cost effectiveness of accelerated partial breast RT compared to on-time and delayed whole breast RT. The design used in this study is decision analytic Markov model. The data sources are published literature; and national/federal sources. The target population of this study is a hypothetical cohort of 60 years old women previously treated with breast-conserving surgery for node-negative, estrogen receptor-positive breast cancer with tumors <1 cm. The time horizon is 15 years, and the perspective is societal. The interventions are whole breast RT, 3-D CRT, and brachytherapy breast irradiation. The outcome measures are costs (2008 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. The base-case results were: 3-D CRT was the preferred strategy, costing on average $10,800 and yielding 11.21 QALYs. On-time whole breast RT costs $368,000/QALY compared to 3-D CRT, above the $100,000/QALY WTP threshold. 3-D CRT was also preferred over delayed whole breast RT. Brachytherapy was never preferred. Sensitivity analysis indicated that the results were sensitive to the rate of recurrence outside the initial tumor quadrant ("elsewhere failure") in one-way analysis. Probabilistic sensitivity analysis indicated that results were sensitive to parameter uncertainty, and that the elsewhere-failure rate and treatment preferences may drive results. The limitation of this study is that efficacy estimates are derived from studies that may not fully represent the population modeled. As a conclusion, 3-D CRT was preferred to whole breast RT and for women likely to delay RT, indicating that 3-D CRT could be targeted more efficiently before randomized trial evidence.

Employment status is related to treatment recovery and quality of life in breast cancer survivors, yet little is known about return to work in immigrant and minority survivors. We conducted an exploratory qualitative study using ethnically cohesive focus groups of urban breast cancer survivors who were African-American, African-Caribbean, Chinese, Filipina, Latina, or non-Latina white. We audio- and video-recorded, transcribed, and thematically coded the focus group discussions and we analyzed the coded transcripts within and across ethnic groups. Seven major themes emerged related to the participants' work experiences after diagnosis: normalcy, acceptance, identity, appearance, privacy, lack of flexibility at work, and employer support. Maintaining a sense of normalcy was cited as a benefit of working by survivors in each group. Acceptance of the cancer diagnosis was most common in the Chinese group and in participants who had a family history of breast cancer; those who described this attitude were likely to continue working throughout the treatment period. Appearance was important among all but the Chinese group and was related to privacy, which many thought was necessary to derive the benefit of normalcy at work. Employer support included schedule flexibility, medical confidentiality, and help maintaining a normal work environment, which was particularly important to our study sample. Overall, we found few differences between the different ethnic groups in our study. These results have important implications for the provision of support services to and clinical management of employed women with breast cancer, as well as for further large-scale research in disparities and employment outcomes.

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