Long-term patterns of in-breast failure in patients with early stage breast cancer treated with breast-conserving therapy: a molecular based clonality evaluation.

BACKGROUND

The clonality of ipsilateral breast tumor recurrences (IBTR) after breast-conserving therapy (BCT) was established using a polymerase chain reaction-based allelic imbalance assay of microsatellite loci to compare tumor suppressor gene alteration patterns.

METHODS

The clonality of IBTRs relative to the initial invasive carcinomas were analyzed using a polymerase chain reaction-based allelic imbalance assay in 57 patients treated with BCT, including both whole breast irradiation and accelerated partial breast irradiation.

RESULTS

Thirty-four IBTRs (60%) were clonally related to the initial carcinoma and 23 (40%) were clonally different. Clonally related IBTRs were more frequently higher grade (70% vs. 32%, P = 0.019) and developed sooner after initial treatment (mean time interval to IBTR was 5.1 years in clonally related versus 9.3 years in clonally different cases [P = 0.002]). Twelve patients subsequently developed distant metastases, of which 9 (75%) had clonally related IBTRs. Clinical IBTR classification and molecular clonality assay results differed in 44% of all cases. The proportion of IBTRs that were clonally related at 5, 10, and 15 years after BCT were 82%, 48%, and 33%, respectively.

CONCLUSIONS

This analysis demonstrates the inaccuracy of clinically establishing the clonality of most IBTRs. Clonally related IBTRs occurred sooner than clonally different IBTRs, were more frequently associated with the development of distant metastases and had a worse prognosis. Molecular clonality assays provide a reliable means of identifying patients who may benefit from aggressive systemic therapy at the time of IBTR and provide an accurate assessment of the efficacy of various forms of local therapy.