Freedman, RA

Abstract Background: Breast cancer care imposes a significant financial burden to U.S. healthcare systems and has become a key focus in the health care debate. Therapies for breast cancer are expensive, and the economic burden of these therapies may be rising due to the rapid introduction of pricey new drugs and techniques. There are limited data on the health care costs of individuals with breast cancer after initial diagnosis and how these costs have changed over time. Methods: We conducted a retrospective analysis of commercially insured adult women with newly diagnosed non-metastatic breast cancer (identified via previously published claims-based algorithms) using 2007-2016 data from a large US health plan available in OptumLabs® Data Warehouse. We included patients with continuous health plan coverage for at least 2 years after initial diagnosis 2007-2014 and assessed how total health care spending and out-of-pocket costs (paid amounts) changed over this time. Costs were adjusted to 2016 US dollars using the general Consumer Price Index. Inpatient, outpatient, and outpatient pharmacy costs were evaluated. A multivariable logistic regression model was used to examine predictors of above average cost (cost > mean for that year of diagnosis). Results: A total of 12,446 newly diagnosed breast cancer patients were identified (mean age, 51.6 years). Forty percent had undergone mastectomy, 38% chemotherapy, and 63% radiation. After adjustment for inflation, total healthcare costs increased 29.7% from 2007 to 2014 (Table 1), with increases primarily observed during the first year after diagnosis. Out-of-pocket costs remained relatively stable, and accounted for 5.3% of the total spending. Approximately 80% of the total costs were related to care received in the outpatient setting. Factors independently associated with above average spending included treatment with mastectomy [OR 1.78 (95% CI 1.5-2.1)], reconstruction [OR 3.0 (95% CI 2.6-3.5)], radiation [OR 4.0 (95% CI 3.4-4.7)] and chemotherapy [OR 18.4 (95% CI 16.6-20.3]. Table 1.Average healthcare spending over time Mean cost during first year after diagnosisMean cost during second year after diagnosisYear of diagnosistotalout-of-pockettotalout-of-pocket2007$80,296.17$4,271.25$16,559.21$1,907.012008$84,126.70$4,445.78$16,785.43$2,205.982009$88,331.45$4,728.42$17,005.68$2,214.932010$91,502.58$5,067.78$17,243.91$2,126.192011$93,826.40$5,089.45$16,862.45$2,027.962012$96,690.06$5,449.91$17,814.09$2,179.262013$104,064.93$5,678.19$17,087.47$2,115.972014$104,169.74$5,620.51$16,714.12$1,590.67 Conclusions: Breast cancer care is increasingly expensive during the first year after diagnosis, and costs are greatest for the recipients of more aggressive treatments. Costs during the second year after diagnosis have remained relatively stable. Citation Format: Ruddy KJ, Sangaralingham LR, Freedman RA, Jemal A, Mougalian SS, Keegan T, Loprinzi CL, Gross CP, Henk HJ, Shah N. Trends in the cost of care for breast cancer among women with commercial insurance [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD6-07.

Abstract Background: Cognitive changes for older women who receive chemotherapy are poorly understood. Methods: Cancer and Leukemia Group B (CALGB) 49907 enrolled 633 women ≥65 years with early stage breast cancer and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). Patients enrolled on the Quality of Life companion study (N = 350) included women who had cognitive and psychological functioning sufficient for providing informed consent and participation in the trial (J Clin Oncol 29:1022, 2011). Participants completed an 18 item questionnaire focusing on their subjective report of cognitive function (attention, problem-solving, speed, new learning, and remote memory) at 6 time points (baseline, mid-treatment, within 1 month post treatment, and at 12, 18, and 24 months post treatment). Possible scores for each item ranged from 1–7 (‘above average’ - ‘severe problem’). Cognitive function score (CFS) was defined as the mean score of items 1–18. Cognitive impairment was defined as CFS 1.5 standard deviations above the overall average baseline. Univariate associations were tested between baseline CFS and patient characteristics (treatment, race, education, number of positive nodes, hormone receptor status, HER2 status, performance status, number of comorbidities, fatigue and depression) using Kruskal-Wallis testing. Frequency distributions were used to describe cognitive impairment. Multivariate analyses were not completed because few women reported subjective cognitive impairment during the study period. Results: 297 assessments were received at baseline, 280 at both mid-treatment and within 1 month post-treatment, 259 at 12 months, 245 at 18 months and 240 at 24 months post-treatment. The median age was 72 (65–85); 32% received AC, 21% CMF, and 47% capecitabine. Most women were white (87%) and had a performance status of 0 (73%). Approximately half of women had a high school degree or less and the majority had stage I-II (78%), hormone-receptor positive (68%) cancers and most did not experience depression or fatigue at baseline. At baseline, the overall mean CFS was 2.1 (‘normal ability’) and 19 women (6%) had mild to severe impairment. Baseline scores did not differ by treatment (p = 0.35). Worse cognitive function at baseline was associated with less education (p < 0.01), increased number of positive nodes (p = 0.02), 4+ comorbid conditions (p < 0.01) and fatigue (p = 0.02), although differences for these groups were small. During the study period, overall mean cognitive function scores remained at ‘normal ability’. At mid-treatment, within 1 month post treatment, 12, 18 and 24 months, cognitive impairment was present in 19 (6%), 19 (6%), 29 (10%), 31 (12%), 18 (7%), and 22 (9%), respectively. Conclusions: Our data suggest that in a healthy group of women without baseline cognitive impairments on objective screening, chemotherapy does not seem to be associated with changes in self-reported cognitive function over time. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-08-05.

Abstract Background: 1/3 of women with metastatic HER2+ breast cancer will develop central nervous system (CNS) metastases yet evidence-based treatments for women with progressive CNS disease are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4 which has promising activity in HER2+ breast cancer. Preclinical evidence suggests it may cross the blood brain barrier. Trial Design: This is a multicenter, phase II, open-label study of neratinib for patients with HER2+ breast cancer and brain metastases. Neratinib is administered at 240 mg orally daily during a 28 day cycle. Two cohorts will be enrolled: Cohort 1 will enroll 40 patients with progressive CNS disease; cohort 2 will enroll ≤5 patients who are candidates for surgical excision of intracranial disease. Surgical candidates receive neratinib 7–21 days preoperatively and resume postoperatively. All patients are re-staged every 2 cycles. Those who develop non-CNS progression have an option to extend therapy with trastuzumab+neratinib. Circulating tumor cells (CTC) are collected at baseline and progression; neurocognitive testing, HADS and EORTC QLQ30/BN20 measures are administered at baseline, cycle 2, cycle 3, and progression (cohort 1). Intracranial tumor, cerebrospinal fluid (CSF), and plasma are collected at surgery (cohort 2). Specific Aims: The primary endpoint is CNS objective response rate (ORR) by composite criteria. Additional endpoints include: non-CNS ORR, progression-free survival, overall survival (OS), site of 1st progression, and toxicity. Correlative and exploratory endpoints include association of CTC count and OS and longitudinal neurocognitive function and quality of life. In an exploratory analysis (cohort 2), we will quantify neratinib concentrations in CSF, intracranial tissue, and plasma and examine associations with response. Eligibility: Patients must have confirmed HER2+ metastatic disease with ≥1 parenchymal brain lesion measuring ≥10 mm that is new or progressed after completing ≥1 line of standard CNS-directed treatment (cohort 1) or CNS disease that is amenable for surgery, including those without prior CNS treatments (cohort 2). Additional eligibility criteria (cohorts 1,2) include: adequate performance status and end organ/marrow function, and ejection fraction ≥50%. Any number of prior lines of therapy is allowed, including prior lapatinib. Statistical Methods: Cohort 1 has a 2-stage design with up to 40 patients. CNS ORR is defined as ≥50% reduction in sum volume of CNS target lesions, without evidence of new lesions, progression of non-target CNS lesions, non-CNS disease progression, worsening neurological symptoms, or increase in corticosteroids. CNS lesion measurements are performed centrally by the Harvard Tumor Imaging Metrics Core. If 1/18 patients have a CNS response in the 1st stage, another 22 patients will enroll. With this design, if ≥5 of 40 patients achieve a CNS response, the drug will be deemed worthy of future study. This 2-stage design has 92% power to distinguish between a true CNS ORR of 20% and a null of 6% (one-sided type I error rate=9%). Accrual: Accrual has begun. Target=45 (cohort 1=40, cohort 2=5) Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-11.