Survival in the Real World: A National Analysis of Patients Treated for Early-Stage Breast Cancer

Abstract

PURPOSE: Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is therefore unclear how treatment outcomes may differ for these patients compared with those who are well-represented in trials. METHODS: This retrospective cohort study included women diagnosed with stage I-III breast cancer between 2005 and 2015 in the national CancerLinQ Discovery electronic medical record–based data set. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those age < 45 or ≥ 70 years were considered under-represented. Patients who were White, age 45-69 years, and without comorbidities were considered well-represented. Cox proportional hazards models were used to evaluate 5-year mortality by representation group and patient characteristics, adjusting for cancer stage, subtype, chemotherapy, and diagnosis year. RESULTS: Of 11,770 included patients, 48% were considered well-represented in trials, 45% under-represented, and 7% unrepresented. Compared with well-represented patients, unrepresented patients had almost three times the hazard of 5-year mortality (adjusted hazard ratio [aHR], 2.71; 95% CI, 2.08 to 3.52). There were no significant differences in the hazard of 5-year mortality for under-represented patients compared with well-represented patients (aHR, 1.19; 95% CI, 0.98 to 1.45). However, among under-represented patients, those age < 45 years had a lower hazard of 5-year mortality (aHR, 0.63; 95% CI, 0.48 to 0.84) and those age ≥ 70 years had a higher hazard of 5-year mortality (aHR, 2.21; 95% CI, 1.76 to 2.77) compared with those age 45-69 years. CONCLUSION: More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision making for all individuals with cancer.

Ineligible, Unaware, or Uninterested? Associations Between Underrepresented Patient Populations and Retention in the Pathway to Cancer Clinical Trial Enrollment

“…The multidecade issue of clinical trial accrual has the potential to exacerbate clinical outcomes (eg, disease, disability, and death) in drugs not typically tested in underrepresented patient populations. 26,27 We expected and found Black patients and patients in areas of higher disadvantage had lower odds of enrollment; however, we found that patients living in rural areas had similar odds of enrollment. We identified that different patient populations had differing odds of retention along the trial enrollment process.…”

Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer

“…These results are at odds with the systematic review of trials on de-escalation in the duration of adjuvant trastuzumab therapy 14 , where a shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS. Other studies and meta-analyses 12 , 24 , however, have shown non-inferiority of 6 months compared to 12 months. These results should be interpreted with caution, as they are based primarily on the Persephone trial 12 , an older trial that employed chemotherapy-trastuzumab regimens considered nonstandard (taxane-free anthracyclines in 90% and sequential trastuzumab in 53% of cases), in a relatively low-risk population (59% of node-negative patients).…”

Applications of Circulating Tumor Cells and Circulating Tumor DNA in Precision Oncology for Breast Cancers

“…Early stage breast cancer is more commonly diagnosed than more advanced breast cancer, but around 20% of these patients have recurrence [ 31 ]. CTCs in the early stages of breast cancer can generate micrometastases and thus are the seeds of the metastatic cascade.…”