Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer

Abstract

Purpose: To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer.

Methods and Materials: Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors ≤ 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors ≤ 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n−]: 396; 1–3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 implant in 298 patients (mean total dose: 15.2 ± 0.07 Gy, range: 15–25 Gy) or by electrons in 225 patients (mean total dose: 14.8 ± 0.09 Gy, range: 5–20 Gy). The mean age was 52.5 ± 0.5 years (range: 26–86 years) and 267 patients were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6 ± 0.3 cm (range: 0.3–3 cm). The intraductal component of the primary tumor was extensive (EIC = IC ≥ 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (≤2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5 ± 1.7 months.

Results: First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60 ± 6 months (median: 47 months, range: 6–217 months) and 49.5 ± 5.4 months (median: 33 months, range: 6–217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78 ± 8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (≤40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7–5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4–6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6–2.8, p = 0.018), and extensive intraductal component (IC <25% vs. IC ≥ 25%; RR: 2.6, 95% CI: 1.3–5.2, p = 0.0075). However, the probability of distant metastatic spread was increased by three different independent factors: the number of involved axillary nodes (RR: 2.2, 95% CI: 1.3–3.8, p = 0.0039), high histologic grade (1 vs. 2 vs. 3; RR: 2, 95% CI: 1.4–3.2, p = 0.00074), isolated local recurrence (no vs. yes; RR: 9.9, 95% CI: 5.5–18, p = 1.8 10⁻¹⁴). Peritumoral vascular invasion significantly influenced the probability of distant metastases in univariate analysis (p = 0.0036) but was not an independent factor in multivariate analysis. Five-year specific survival after local recurrence was influenced only by disease-free interval from the beginning of treatment to local recurrence (≤2 years vs. >2 years; RR: 4.8, 95% CI: 1.2–19, p = 0.026).

Conclusions: In this series, the risk of distant metastases increased with increased incidence of isolated local recurrences. However, the predicting factors for local recurrence and distant metastases seemed to differ. In addition, after local recurrence, the disease-free interval from the beginning of treatment to local recurrence influenced specific survival.