Changes in management techniques and patterns of disease recurrence over time in patients with breast carcinoma treated with breast-conserving therapy at a single institution.

BACKGROUND: The authors reviewed changes in the initial clinical presentation, management techniques, and patterns of disease recurrence over time (1981-1996) in patients with breast carcinoma treated with breast-conserving therapy (BCT) at a single institution. The goals of the current study were to determine the frequency and use of optimal local and systemic therapy techniques and to evaluate the impact of these changes on treatment efficacy. METHODS: Six hundred seven patients with American Joint Committee on Cancer Stage I or II invasive breast carcinomas treated with BCT at William Beaumont Hospital (Royal Oak, MI) constituted the study population. All patients received at least an excisional biopsy of the primary tumor, an axillary lymph node staging procedure, and postoperative radiotherapy (RT) (a median tumor bed dose of 61 Gray [Gy] was administered). All sides were reviewed by one pathologist. Numerous clinicopathologic and treatment-related factors were analyzed to monitor changes that occurred over time. Changes in patterns of disease recurrence and treatment efficacy over time also were analyzed. RESULTS: Over the time period analyzed, changes at initial presentation included an increase in the mean age at diagnosis (age 56.1 years vs. 61.4 years; P < 0.001), a decrease in the number of patients with clinically palpable tumors (78% vs. 36%; P < 0.001), a decrease in the mean tumor size (2.2 cm vs. 1.6 cm; P < 0.001), but no change in the percentage of patients with negative lymph nodes (79% vs. 78%; P = 0.83). No differences over time were observed in mean tumor grade (2.0 vs. 1.9; P = 0.2) or the presence of angiolymphatic invasion (27% vs. 26%; P = 0.25). Changes in surgical management and pathologic assessment included the more frequent use of reexcision (46% vs. 81%; P < 0.001), larger mean total volumes of breast tissue specimens excised (115 cm3 vs. 189 cm3; P = 0.001), a larger percentage of patients with final negative surgical margins (74% vs. 97%; P < 0.001), and a small increase in the mean number of lymph nodes excised (13.8 lymph nodes vs. 14.1 lymph nodes; P = 0.01). The only other significant change in the pathologic management of patients over time included a doubling in the mean number of slides examined (10.6 slides vs. 21.1 slides; P < 0.001). Changes in adjuvant local and systemic therapy included an increase in the percentage of patients treated with > 60 Gy to the tumor bed (66% vs. 95%; P < 0.001), a doubling in the mean number of days from the last surgery to the start of RT (24 days vs. 50 days; P < 0.001), and a decrease in the use of regional lymph node RT (24% vs. 8%; P < 0.001). The use of adjuvant tamoxifen increased from 10% to 61% (P < 0.001). Finally, improvements were observed in the 5-year and 12-year actuarial rates of local disease recurrence (8% vs. 1% and 21% vs. 9%, respectively; P = 0.001) and distant metastases (12% vs. 4% and 22% vs. 9%, respectively; P = 0.006). No changes in the mean number of years to ipsilateral (6.5 years vs. 6.4 years; P = 0.59) or distant disease recurrence (4.6 years vs. 3.8 years; P = 0.73) were observed. CONCLUSIONS: The impact of screening mammography and substantial changes in surgical, pathologic, RT, and systemic therapy recommendations were observed over time in the study population. These changes were associated with improvements in 5-year and 12-year local and distant control rates and suggested that improvements in outcome can be realized through adherence to best practice guidelines and continuous monitoring of treatment outcome data.

Risk factors for regional nodal failure after breast-conserving therapy: regional nodal irradiation reduces rate of axillary failure in patients with four or more positive lymph nodes.

PURPOSE: To determine the incidence of, and risk factors for, regional nodal failure (RNF) and to evaluate the effectiveness of, and indications for, regional nodal irradiation (RNI) in patients with Stage I-II breast cancer treated with breast-conserving therapy. METHOD AND MATERIALS: A total of 1500 cases of Stage I-II breast cancer were treated with breast-conserving therapy between February 1980 and December 2000. All patients underwent excisional biopsy, and 925 (62%) underwent re-excision. Level I-II axillary lymph node dissection was done in 94% of patients. The lymph nodes were pathologically involved in 335 patients (22%); 255 with 1-3 nodes and 80 with >/=4 nodes involved. All patients received whole breast irradiation to a median dose of 45 Gy, and 97% received a tumor bed boost to a median dose of 61 Gy. Treatment included the breast only in 1309 patients (87%), and the breast and regional lymphatics in 191 (13%). RESULTS: With a median follow-up of 8.1 years, 35 patients had failure within the regional nodes: 12 patients (6%) who received RNI and 23 patients (2%) who did not. The 5- and 10-year rate for any RNF was 1.9% and 2.8%, respectively. The 5 and 10-year rates of axillary failure and supraclavicular failure were 0.6% and 1.0% and 0.9% and 1.6%, respectively. In patients with >/=4 positive lymph nodes, RNI reduced the 10-year rate of any RNF from 11% to 2% (p = 0.024), the rate of axillary failure from 5% to 0% (p = 0.019), and the rate of supraclavicular failure from 11% to 2% (p = 0.114). RNI did not affect the rate of axillary failure or supraclavicular failure in patients with 1-3 positive nodes. In node-negative patients, the rate of RNF was significantly greater if <6 nodes were removed at the time of axillary dissection. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with RNF. On univariate analysis, RNF was associated with the number of nodes excised, number of positive nodes, percentage of positive nodes, size of nodal metastasis, presence of angiolymphatic invasion, estrogen receptor status, age, systemic chemotherapy, and RNI. Three subsets of patients had unusually high rates of RNF, those with >/=67% nodes positive (16%), nodal metastasis >/=2.0 cm (44%), or age 10 nodes excised, respectively (p = 0.05). CONCLUSION: Failure within the regional lymph nodes as an isolated site of first relapse is uncommon in patients with Stage I-II breast cancer treated with breast-conserving therapy. RNI can significantly reduce the rate of RNF (axillary failure) in patients with >/=4 positive lymph nodes. The maximal size of the lymph node metastasis was found to be the only significant independent predictor of RNF, with nodal metastases >/=2.0 cm associated with extremely high regional failure rates. Despite this, young age and the extent of axillary dissection (particularly as related to the number of positive nodes) also appear to be important and should be considered when evaluating patients for RNI. Inadequate axillary dissection was not only associated with increased regional failure, but also reduced survival.