Towards a New Adjuvant Chemotherapy Selection Procedure for Elderly Patients with Early Breast Cancer Using PREDICT Tool and CRASH Score

Background: Fit older women, of whatever age, should benefit from optimal adjuvant therapy. The purpose of this study was to develop an algorithm to assist oncologists validate chemotherapy for early-stage breast cancer in elderly patients. Methods: Patients over 70 with early-stage breast cancer and a standardised Comprehensive Geriatric Assessment made at baseline were screened. Several data, including oncogeriatric data, were collected and analysed. Next, we assessed the benefit/risk balance of a therapeutic strategy escalation with simulated efficacy (PREDICT tool) and tolerability data (CRASH score). For each cohort, we differentiated the survival benefit from chemotherapy and simulated heme, non-heme and combined risks of chemo-induced toxicities. Finally, we defined 3 new study cohorts based on simulated survival benefit. In conclusion, we presented a decision algorithm with therapeutic escalation or de-escalation strategy (EEBC algorithm). Findings: Even though 74% of the patients had been initially assigned to chemotherapy, only 34% had finally received this treatment. Significant geriatric differences were found between patients given an initial decision to receive chemotherapy, or not, but these differences were almost absent in patients with completed surgery. Treatment without chemotherapy was expected to result in a 5-year OS loss of 3·2%-4·0%. No additional chemo-induced toxicities were expected. In simulated cohorts, patients with the highest expected gain after 5 years (16·7%) and the highest expected benefit from chemotherapy (9·5%) had the lowest proposed chemotherapy rate (73·1%) despite the absence of expected additional simulated chemo-induced toxicities. Finally, the EEBC algorithm proposed 62% de-escalation and 38% escalation approaches. Interpretation: A large majority of patients eligible for completed surgery should also be eligible for chemotherapy. Selected patients may benefit from chemotherapy without the anticipated additional chemo-induced side-effects. Results should be confirmed in a validation cohort and the algorithm should be tested in a randomised study comparing usual practice versus EEBC-guided practice. Funding Statement: The authors declared: None. Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by an ethics committee. Patients gave informed consent at the first consultation with a geriatrician to their inclusion in the cohort and were registered at baseline in compliance with the French Database and Privacy Law (CNIL, registration number CILS:188).