True recurrence vs. new primary ipsilateral breast tumor relapse: An analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management

Purpose: The purpose of this study was to classify ail ipsilateral breast t umor relapses (IBTR) in patients treated with conservative surgery and radi ation therapy (CS+RT) as either new primary tumors (NP) or true local recur rences (TR) and to assess the prognostic and therapeutic implications of th is classification. Methods and Materials: Of the 1152 patients who have been treated at Yale-N ew Haven Hospital before 1990, 136 patients have experienced IBTR as their primary site of failure. These relapses were classified as either NP or TR. Specifically, patients were classified as NP if the recurrence was distinc tly different from the primary tumor with respect to the histologic subtype , the recurrence location was in a different location, or if the flow cytom etry changed from aneuploid to diploid. This information was determined by a detailed review of each patient's hospital and/or radiotherapy record, ma mmograms, and pathologic reports. Results: As of 2/99, with a mean follow-up of 14.2 years, the overall ipsil ateral breast relapse-free rate for all 1152 patients was 86% at 10 years. Using the classification scheme outlined above, 60 patient relapses were cl assified as TR, 70 were classified as NP and 6 were unable to be classified . NP patients had a longer mean time to breast relapse than TR patients (7. 3 years vs. 3.7 years, p < 0.0001) and were significantly younger than TR p atients (48.9 years vs. 54.5 years, p < 0.01). Patients developed both TR a nd NP at similar rates until approximately 8 years, when TR rates stabilize d but NP rates continued to rise. By 15 years following original diagnosis, the TR rate was 6.8% compared to 13.1% for NP. Of the patients who had bee n previously tested for BRCA1/2 mutations, 17% (8/52) had deleterious mutat ions. It is noteworthy that all patients with deleterious mutations had new primary IBTR, while patients without deleterious mutations had both TR and NP (p = 0.06). Ploidy was evenly distributed between TR and NP but KP had a significantly lower S phase fraction (NP 13.1 vs. TR 22.0, p < 0.05). The overall survival following breast relapse was 64% at 10 years and 49% at 1 5 years. With a mean follow-up of 10.4 years following breast relapse, pati ents,vith NP had better 10-year overall survival (TR 55% vs. NP 75%, p < 0. 0001), distant disease-free survival (TR 41% vs, NP 85%,p < 0.0001), and ca use-specific survival (TR 55% vs. NP 90%,p < 0.0001). Conclusion: It appears that a significant portion of patients who experienc e ipsilateral breast tumor relapse following conservative surgery and radia tion therapy have new primary tumors as opposed to true local recurrences. True recurrence and new primary tumor ipsilateral breast tumor relapses hav e different natural histories, different prognoses, and, in turn, different implications for therapeutic management. (C) 2000 Elsevier Science Inc.