Schnitt S J, Hayman J, Gelman R, Eberlein T J, Love S M, Mayzel K, Osteen R T, Nixon A J, Pierce S, Connolly J L, Cohen P, Schneider L, Silver B, Recht A, Harris J R
Department of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer. 1996 Mar 15;77(6):1094-100.
Randomized clinical trials have clearly demonstrated that the use of radiation therapy (RT) following breast-conserving surgery (CS) substantially reduces the risk of local recurrence. However, the low rate of local recurrence after CS and RT for patients without known risk factors, and the recent increase in the detection of smaller cancers due to mammographic screening have led to the speculation that a subgroup of patients who have a low risk of local recurrence without RT might be identified. In 1986, we initiated a one-arm, prospective clinical trial of CS alone for treatment of highly selected breast cancer patients without known risk factors for local recurrence.
The study had a sequential design with a planned accrual of 90 patients. Criteria for entry into the trial were: a unicentric, clinical TI infiltrating ductal, mucinous or tubular carcinoma without an extensive intraductal component or lymphatic vessel invasion; a wide excision with a pathologically-documented negative margin of at least 1 cm; and histologically negative axillary lymph nodes. No adjuvant RT or systemic therapy was administered. Seventy-six per cent of the lesions were detected by mammography alone. The median gross pathologic tumor size was 0.9 cm. The median patient age was 67 years.
Eighty-seven patients were enrolled in the trial before it closed prematurely in 1992 because the predefined stopping boundary was crossed (i.e., the sixth local recurrence was observed). At that time, the average annual local recurrence rate was 4.2%. With a median follow-up of 56 months, there are now 14 patients (16%) with local recurrence as their site of first failure (average annual local recurrence rate: 3.6%). Four patients without local recurrence developed distant metastases. Three patients have died, one of metastatic breast cancer and two of unrelated causes.
Even in a highly selected group of patients with early-stage breast cancer, there is a substantial risk of early local recurrence for those treated with wide excision alone.
随机临床试验已明确表明，保乳手术（CS）后使用放射治疗（RT）可大幅降低局部复发风险。然而，对于无已知风险因素的患者，CS联合RT后的局部复发率较低，且由于乳腺钼靶筛查导致较小癌症的检出率近期有所增加，这引发了一种推测，即可能识别出一组无需RT即可发生局部复发风险较低的患者亚组。1986年，我们启动了一项单臂前瞻性临床试验，仅对高度选择的无局部复发已知风险因素的乳腺癌患者进行CS治疗。
该研究采用序贯设计，计划纳入90例患者。纳入试验的标准为：单中心、临床T1浸润性导管癌、黏液癌或管状癌，无广泛导管内成分或淋巴管侵犯；广泛切除，病理记录切缘阴性至少1 cm；腋窝淋巴结组织学阴性。未给予辅助RT或全身治疗。76%的病变仅通过乳腺钼靶检查发现。大体病理肿瘤大小中位数为0.9 cm。患者年龄中位数为67岁。
1992年试验提前结束前共纳入87例患者，原因是越过了预先设定的停止界限（即观察到第6例局部复发）。当时，平均年局部复发率为4.2%。中位随访56个月后，现有14例患者（16%）以局部复发作为首次失败部位（平均年局部复发率：3.6%）。4例无局部复发的患者发生远处转移。3例患者死亡，1例死于转移性乳腺癌，2例死于无关原因。
即使在高度选择的早期乳腺癌患者组中，仅行广泛切除治疗的患者仍有较高的早期局部复发风险。
