Sarah Schellhorn Mougalian

Neoadjuvant Chemotherapy for Breast Cancer Increases the Rate of Breast Conservation: Results from the National Cancer Database

BACKGROUND Neoadjuvant chemotherapy has been shown to increase the rate of breast conservation in clinical trials and small institutional series, but it has never been studied on a national level. STUDY DESIGN We performed a retrospective review of the National Cancer Database (NCDB). The NCDB is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society and contains about 80% of the cancer cases in the United States. All women in the NCDB diagnosed with invasive breast cancer from 2006 through 2011, who underwent definitive breast surgery and received either neoadjuvant or adjuvant chemotherapy, excluding patients with distant metastases or T4 tumors, were included and rates of breast preservation were determined. RESULTS Of 354,204 patients who met the inclusion criteria, 59,063 (16.7%) underwent neoadjuvant chemotherapy. This proportion steadily increased from 13.9% in 2006 to 20.5% in 2011 (p<0.001). Receipt of neoadjuvant chemotherapy was associated with larger tumor size (7% cT1, 25% cT2, and 58% cT3; p<0.001), more advanced nodal disease (11% cN0, 39% cN1-3; p<0.001), younger patient age (21%<50 years vs 14%>50 years; p<0.001), higher tumor grade (18% grade 3, 15% grade 2, vs 12% grade 1; p<0.001), and estrogen receptor (ER)-negative tumors (21% ER negative vs 15% ER postive; p<0.001). Multivariate logistic regression showed that when adjusted for the above variables, patients with tumors larger than 3 cm undergoing neoadjuvant chemotherapy were more likely to receive breast preservation than those who opted for primary surgery (odds ratio 1.7, 95% CI 1.6 to 1.8). CONCLUSIONS Neoadjuvant chemotherapy increases breast preservation for patients with breast tumor size larger than 3 cm.

Adoption of hypofractionated whole-breast irradiation for early-stage breast cancer: a National Cancer Data Base analysis.

PURPOSE To evaluate the relationship of patient, hospital, and cancer characteristics with the adoption of hypofractionation in a national sample of patients diagnosed with early-stage breast cancer. METHODS AND MATERIALS We performed a retrospective study of breast cancer patients in the National Cancer Data Base from 2004-2011 who were treated with radiation therapy and met eligibility criteria for hypofractionation. We used logistic regression to identify factors associated with receipt of hypofractionation (vs conventional fractionation). RESULTS We identified 13,271 women (11.7%) and 99,996 women (88.3%) with early-stage breast cancer who were treated with hypofractionation and conventional fractionation, respectively. The use of hypofractionation increased significantly, with 5.4% of patients receiving it in 2004 compared with 22.8% in 2011 (P<.001 for trend). Patients living ≥50 miles from the cancer reporting facility had increased odds of receiving hypofractionation (odds ratio 1.57 [95% confidence interval 1.44-1.72], P<.001). Adoption of hypofractionation was associated with treatment at an academic center (P<.001) and living in an area with high median income (P<.001). Hypofractionation was less likely to be used in patients with high-risk disease, such as increased tumor size (P<.001) or poorly differentiated histologic grade (P<.001). CONCLUSIONS The use of hypofractionation is rising and is associated with increased travel distance and treatment at an academic center. Further adoption of hypofractionation may be tempered by both clinical and nonclinical concerns.

Racial Differences in the Use and Outcome of Neoadjuvant Chemotherapy for Breast Cancer: Results From the National Cancer Data Base

PURPOSE To explore racial differences in the use and outcome of neoadjuvant chemotherapy for breast cancer. METHODS The National Cancer Data Base was queried to identify women with stage 1 to 3 breast cancer diagnosed in 2010 and 2011. Chemotherapy use and rate of pathologic complete response (pCR) was determined for various racial/ethnic groups. RESULTS Of 278,815 patients with known race and ethnicity, 127,417 (46%) received chemotherapy, and of 121,446 where the timing of chemotherapy was known, 27,300 (23%) received neoadjuvant chemotherapy. Chemotherapy, and neoadjuvant chemotherapy in particular, was given more frequently to black, Hispanic, and Asian women than to white women (P < 0.001). This difference was largely explained by more advanced stage, higher grade tumors, and a greater proportion of triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumors in these women. Of 17,970 patients with known outcome, 5,944 (33%) had a pCR. No differences in response rate for estrogen receptor (ER)/progesterone receptor (PR)-positive tumors were found, but compared with white women, black but not Hispanic or Asian women had a lower rate of pCR for ER/PR-negative, HER2-positive (43% v 54%, P = 0.001) and triple-negative tumors (37% v 43%, P < 0.001). This difference persisted when adjusted for age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patients zip code (odds ratio, 0.84; 95% CI, 0.77 to 0.93). CONCLUSION Neoadjuvant chemotherapy is given more frequently to black, Hispanic, and Asian women than to white women. Black women have a lower likelihood of pCR for triple-negative and HER2-positive breast cancer. Whether this is due to biologic differences in chemosensitivity or to treatment or socioeconomic differences that could not be adjusted for is unknown.

Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

PURPOSE Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. METHODS AND MATERIALS We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). RESULTS We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. CONCLUSIONS The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

Association of 21-gene recurrence score assay and adjuvant chemotherapy use in the medicare population, 2008-2011.

OBJECTIVES The 21-gene recurrence score (RS) assay helps guide adjuvant chemotherapy use for patients with breast cancer, and is predicted to reduce overall chemotherapy use. Little is known about recent patterns of testing in the Medicare program and the impact of testing on chemotherapy use as a function of patient age. MATERIALS AND METHODS We conducted a national claims-based study of Medicare beneficiaries age ≥ 66 years. We assessed trends in assay use (using multivariable regression), adjuvant chemotherapy use, and associated expenditures, for all patients and for two age strata: age 66-74 years and 75-94 years. Geographic variations in assay adoption and regional-level correlation between assay and chemotherapy use were measured. RESULTS We identified 132,222 women who underwent breast surgery from 2008-2011. Assay use increased from 9.0% to 17.2% from 2008-2011 (p<.001), but chemotherapy use remained stable at 12.5% (p=.49). In younger patients, assay use increased from 14.3% to 23.7% (p<.001), while chemotherapy use decreased from 18.2% to 16.2% (p<.001). In older patients, assay use increased from 4.1% to 9.9% (p<.001), while chemotherapy use remained stable at 6.8% (p=.67). Mean per-beneficiary expenditures for testing and chemotherapy increased from

Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal

2030 to

Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant Therapy Decision Making

2430 (p<.001). Regions with increased assay adoption were not more likely to reduce chemotherapy. CONCLUSION Despite increased RS testing for both younger and older Medicare patients, there has only been a modest decrease in chemotherapy use for younger patients and no change for older patients, resulting in an overall increase in costs associated with gene expression profiling.

Feasibility and savings of a suspicion of cancer clinic at a large county hospital.

Purpose Prior studies examining cost effectiveness of the 21-gene assay (Oncotype DX [ODX]) for women with hormone receptor-positive, early-stage breast cancer have yielded disparate results. We aimed to explore why these analyses may have yielded different conclusions. Methods We conducted a systematic literature review of cost-effectiveness analyses (CEAs) of ODX. We examined the extent to which the structure of CEA modeling, the assumptions of the models, and the selection of input parameters influenced cost-effectiveness estimates. We also explored the prevalence of industry funding and whether industry funding was associated with study designs favoring ODX. Results We identified 27 analyses, 15 of which received industry funding. In 18 studies, the clinical characteristics (eg, tumor size and grade) commonly used to make chemotherapy decisions were not incorporated into simulation modeling; thus, these studies would favor ODX being cost effective and might not reflect clinical practice. Most studies ignored the heterogeneous effect of ODX on chemotherapy use; only five studies assumed that ODX would increase chemotherapy use for clinically low-risk patients but decrease chemotherapy use for clinically high-risk patients. No study used population-based joint distributions of ODX recurrence score and tumor characteristics, and 12 studies inappropriately assumed that chemotherapy would increase distant recurrence for the low recurrence score group; both approaches overestimated the benefits of ODX. Industry-funded studies tended to favor ODX; all five studies that reported ODX as being cost saving were industry funded. In contrast, two studies that reported an incremental cost-effectiveness ratio >

Risk of myeloid neoplasms after radiotherapy among older women with localized breast cancer: A population-based study

50,000 per quality-adjusted life-year were not funded by industry. Conclusion Although a majority of published analyses indicated that ODX is cost effective, they incorporated study designs that can increase the risk of bias.

Bone Density Screening in Postmenopausal Women With Early-Stage Breast Cancer Treated With Aromatase Inhibitors

PURPOSE The 21-gene recurrence score (RS) assay is used to help formulate adjuvant chemotherapy recommendations for patients with estrogen receptor-positive, early-stage breast cancer. Most frequently, medical oncologists order RS after surgery. Results take an additional 2 weeks to return, which can delay decision making. We conducted a prospective quality-improvement project to assess the impact of early guideline-directed RS ordering by surgeons before the first visit with a medical oncologist on adjuvant therapy decision making. MATERIALS AND METHODS Surgical oncologists ordered RS testing following National Comprehensive Cancer Network guidelines at time of diagnosis or at time of surgery between July 1, 2015 and December 31, 2015. We measured the testing rate of patients eligible for RS, time to chemotherapy decisions, rates of chemotherapy use, accrual to RS-based clinical trials, cost, and physician acceptance of the policy and compared the results to patients who met eligibility criteria for early guideline-directed testing during the 6 months before the project. RESULTS Ninety patients met eligibility criteria during the testing period. RS was ordered for 91% of patients in the early testing group compared with 76% of historical controls ( P < .001). Median time to chemotherapy decision was significantly shorter in the early testing group (20 days; 95% CI, 17 to 23 days) compared with historical controls (32 days; 95% CI, 29 to 35 days; P < .001). There were no significant differences in time to chemotherapy initiation, chemotherapy use, RS-based trial enrollment, or calculated costs between the groups. CONCLUSION Early guideline-directed RS testing in selected patients is an effective way to shorten time to treatment decisions.