Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

BACKGROUND: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. METHODS: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. RESULTS: Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. CONCLUSIONS: TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. LAY SUMMARY: The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Does age affect outcome with breast cancer?

Prior data about the influence of age at diagnosis of breast cancer on patient outcomes and survival has been conflicting. Using the Breast Cancer Outcomes Unit database at BC Cancer, this retrospective population-based study identified a cohort of 24,469 patients diagnosed with invasive breast cancer between 2005 and 2014. Median follow-up was 11.5 years. We analyzed clinical and pathological features at diagnosis and treatment specific variables compared across the following age cohorts: <35, 35-39, 40-49, 50-59, 60-69, 70-79, and 80 years of age and older. We assessed the impact of age on breast cancer specific survival (BCSS) and overall survival (OS) by age and subtype. There were distinct clinical-pathological and treatment pattern differences at both extremes of age at diagnosis. Patients <35 and 35-39 years old were more likely to present with higher risk features, HER2 positive or triple-negative biomarkers, and more advanced TNM stage at diagnosis. They were more likely to undergo treatment with mastectomy, axillary lymph node dissection, radiotherapy and chemotherapy. Conversely, patients ≥80 years old were generally more likely to have hormone-sensitive HER2-negative disease, and lower TNM stage at diagnosis. They were less likely to undergo surgery or be treated with radiotherapy and chemotherapy. Both younger and elderly age at breast cancer diagnosis were independent risk factors for poorer prognosis after controlling for subtype, LVI, stage, and treatment factors. This work will help clinicians to more accurately estimate patient outcomes, patterns of relapse, and provide evidence-based treatment recommendations.

pN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era.

PURPOSE: Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment. METHODS AND MATERIALS: We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer. Outcomes were 10-year Kaplan-Meier LRRFS, relapse-free survival (RFS), distant relapse-free survival, and breast cancer-specific survival. Multivariable analysis of LRRFS and RFS was performed in pN0(i+) and pN1mi cohorts. RESULTS: Median follow-up was 9.3 years. In patients with pN0 (n = 7492), pN0(i+) (n = 305), pN1mi (n = 619), and pN1a (n = 1855) disease, LRRT was used in 1.1%, 24.3%, 45.7%, and 71.1%, respectively. Ten-year outcomes were LRRFS 96%, 92%, 97%, and 96% (P < .001), distant RFS 94%, 91%, 90%, and 84% (P < .001), and breast cancer-specific survival 95%, 90%, 93%, and 87% (P < .001), respectively. Ten-year LRRFS for patients treated with breast-conserving surgery alone, with breast RT, and with LRRT were 81%, 93%, and 91% for patients with pN0(i+) (P = .16) and 94%, 96%, and 100% for patients with pN1mi (P = .02), respectively. Among patients treated with mastectomy, 10-year LRRFS with surgery alone and with LRRT were 93% and 100% for patients with pN0(i+) (P = .12) and 95% and 99% for patients with pN1mi (P = .09). On multivariable analysis of patients with pN0(i+) and pN1mi, systemic therapy was associated with improved LRRFS in patients with pN0(i+) (hazard ratio [HR], 0.2; [0.06-0.6]; P = .005) and patients with pN1mi (HR, 0.1; [0.03-0.5]; P = .006). In patients with pN1mi, LRRT was associated with a trend toward increased LRRFS (HR, 0.2; [0.03-1.1]; P = .07). LRRT was not significantly associated with improved RFS in pN0(i+) or pN1mi disease. CONCLUSIONS: In the era of sentinel node staging and modern systemic therapy, patients with pN0(i+) and PN1mi treated with LRRT experienced 10-year LRR risks ≤10% after breast-conserving surgery or mastectomy and RT. LRRT was associated with a trend toward increased LRRFS in pN1mi but not pN0(i+) disease.

Local Relapse After Breast-Conserving Therapy Versus Mastectomy for Extensive Pure Ductal Carcinoma In Situ ≥4 cm.

PURPOSE: The optimal treatment for patients with extensive pure ductal carcinoma in situ (DCIS) ≥4 cm is controversial. This study evaluates local relapse according to type of local therapy: mastectomy, breast-conserving surgery (BCS) alone, and BCS + radiation therapy (RT). METHODS AND MATERIALS: Subjects were female patients who received diagnoses of pure DCIS ≥4 cm between 1989 and 2010 and were referred to British Columbia Cancer. Clinicopathologic and treatment characteristics were compared between treatment cohorts. Local relapse (LR) was estimated using competing risk analysis. Multivariable analysis was performed using Cox regression analysis. RESULTS: Patients had the following treatments: 490 mastectomy, 38 BCS alone, and 192 BCS + RT. The 10-year cumulative incidence of LR was 16% after BCS (95% confidence interval [CI], 6-29%), 8% after BCS + RT (95% CI, 4-12%), and 2% after mastectomy (95% CI, 1-4%). On multivariable analysis, estrogen receptor-negative disease (hazard ratio [HR], 3.32; 95% CI, 1.08-10.18; P = .04) and positive margins (HR, 3.55; 95% CI, 1.56-8.05; P = .002) were associated with increased LR. BCS alone (HR, 7.87; 95% CI, 2.82-21.92; P < .0001), BCS + RT + no boost (HR, 3.80; 95% CI, 1.56-9.28; P = .003), and BCS + RT + boost (HR, 5.76; 95% CI, 2.59-12.83; P < .0001) were all associated with a higher risk of relapse relative to mastectomy. CONCLUSIONS: Mastectomy remains a standard local treatment option for extensive DCIS, but BCS + RT may also be reasonably considered in selected patients with a careful discussion of the benefits, side effects, and patient preferences.