Predictors of systemic recurrence and impact of local failure among early stage breast cancer patients treated with breast conserving therapy

Introduction: Our aim was to determine predictors of systemic recurrence (SR), and the impact of prior local failure (LF) in stage I-II breast cancer patients (pts) treated with breast conserving therapy (BCT) with long-term follow-up. Methods: Between 1970 and 1994, 1152 consecutive female pts with stage I-II breast cancer underwent BCT at our institution. Pts with prior breast cancer or other primary malignancies (n=70) and with LF alone (n=69) were excluded. Variables evaluated included; age, race, tumor size, stage, pathological tumor margins, axillary node involvement, estrogen/progesterone receptors, Black's nuclear grade, axillary node dissection, and use of adjuvant therapy. Results: Among the 1013 pts, 53% presented with stage I, and 47% with stage II disease. Median age was 50 years (yrs) with median follow-up of 9 yrs (range: 0.25-29). Axillary nodes were positive in 233 pts (27%). Fifty-six pts (5%) developed local failure followed by systemic recurrence (LF→SR), 136 pts (13%) systemic recurrence alone (SR) and 821 pts (76%) were without recurrence (NR). Pts with younger age, small tumors, positive margins, lumpectomy alone, and without chemotherapy or hormonal therapy were more likely to develop LF followed by SR. Median time to develop SR was 3.6 yrs. In pts with LF followed by SR, median time to LF was 4 yrs, and median time between LF, and SR was 1.1 yrs. Significant independent predictors of SR by mullivariate analysis were non-use of tamoxifen and presence of axillary nodal metastases. Overall 10-yr survival among pts with LF→SR versus SR was 56% and 30% respectively (p=0.04). Sites of distant metastases were; bone, lung, liver, brain, and supraclavicular lymph nodes. Patients with prior LF had significantly longer median time to distant metastases when compared to those with SR alone (6.5 yrs vs. 3 yrs; p= <0.001). Conclusions: Approximately 50% of patients with local failure subsequently develop systemic recurrence, and median time to systemic recurrence among these patients is one year. Breast conserving therapy patients that develop local failure should be treated aggressively with multi-modality therapy.