De-escalating and escalating systemic therapy in triple negative breast cancer.

Triple negative breast cancer has the highest relapse risk of all the clinical subsets, although the escalation of chemotherapy has benefited this subset substantially over recent years. Systemic options are limited to chemotherapy, which makes meaningful de-escalation or escalation of therapy more challenging but possible. Observational cohorts suggest a less than 10% risk of relapse and minimal if any benefit of chemotherapy in very small (<1 cm), node-negative triple negative disease. In higher risk, particularly node-positive disease, anthracycline/taxane-based regimens remain standard. Neoadjuvant chemotherapy clearly de-escalates surgery, although there are insufficient data to give less than standard chemotherapy on the basis of response to neoadjuvant therapy. Efforts to meaningfully escalate therapy in high-risk disease have included incorporating platinums into Neoadjuvant therapy, with clear benefit in pCR but uncertain impact on relapse and survival at this time. Residual disease after neoadjuvant chemotherapy carries a particularly poor prognosis; a recent randomized trial of 6 months' capecitabine in this setting suggested a survival advantage to this approach in higher risk residual disease. While not validated at this time, future directions are likely to include biologic prognostication with tumor and immune variables, as well as targeted non-cytotoxic approaches leveraging the molecular heterogeneity of triple negative disease.