Does Tumor Marking Before Neoadjuvant Chemotherapy Helps Achieve Better Outcomes in Patients Undergoing Breast Conservative Surgery? A Systematic Review

Patients with breast cancer are increasingly being offered breast conserving surgery (BCS) following neoadjuvant chemotherapy (NACT). We aimed to conduct a systematic review to assess the advantage of tumor marking in patients undergoing BCS after NACT. After registering the protocol for a systematic review with PROSPERO, a systematic search was conducted through September 30, 2020, for all studies involving patients undergoing BCS post NACT after tumor marking. Margin status on final histology was the primary outcome. Oxford Centre for Evidence Based Medicine (OCEBM) levels were used to assess internal validity. A total of 636 records from Medline/PubMed, 1381 from Embase, and 1422 from Cochrane library were extracted. After screening, 15 articles (1520 patients) were included for data synthesis. For marking, 6 studies used metallic markers and 5 used I-125-radioactive seeds (RSL) followed by skin tattoo and radio-guided occult lesion localization using Tc-99m (ROLL) in one study each. Most studies used a single marker at the center except for two (143 patients), who practiced the bracketing technique. Incidence of unsatisfactory margins (positive/close) ranged from 5 to 23.5%. After excluding patients with complete pathological response, the "adjusted unsatisfactory margin" rate was found to be 19.3% (10.4-33%). Overall 20.6 recurrences (locoregional/distant) were reported per 1000 patient-years follow-up. Overall survival (OS) was only reported by one study as 96.6% and 84.7% in patients with and without marker placement (p = .01). Re-excision and secondary mastectomy rates (reported by nine studies) were 7.3% and 5.7% respectively. There is limited evidence that tumor marking before neoadjuvant chemotherapy improves the rate of unsatisfactory margins or survival outcomes in a patient undergoing BCS after NACT.