手术切缘小对乳腺癌患者不利

在肿瘤外科学会(SSO)年度癌症研讨会上公布的研究显示，对于乳腺癌患者而言，缩小手术切缘可能反而带来大问题。一项针对2,377例接受保乳治疗或乳房切除术的女性患者结局的回顾性研究显示，对于所有患者，切缘＜2 mm可导致显著的残留疾病风险。另一项研究对接受乳房切除术的导管原位癌(DCIS)女性随访10年发现，局部区域复发(LRR)率随手术切缘缩小而增加，并且临近切缘是LRR的唯一独立预测因素。

Erin M. Garvey博士

在第一项研究中，亚利桑那州凤凰城梅奥医院的Erin Garvey博士及其同事假设，手术切缘≥1 mm的无广泛原位成分的浸润性导管癌患者在再次切除时将无残留疾病证据。为了检验这一假设，研究者回顾性分析了一个前瞻性数据库收录的2000年1月~2012年5月间接受2,520例手术的2,377例患者数据。其中1,498例(63%)患者接受肿块切除术，182例(12%)需再次切除：10%仅接受保乳手术，2%改为乳房切除术。在158例再次切除后完成保乳治疗的患者中，50例(32%)存在残留疾病，在27例手术改为乳房切除术的患者中，20例存在残留疾病。

在37%(879例)接受预先乳房切除术的患者中，2%(19例)接受再次切除，其中5例患者存在残留疾病。总体而言，在具有阳性切缘的患者中，40%存在残留疾病，而在切缘0.1~0.9 mm的患者中，38%存在残留疾病，在切缘1.0~1.9 mm的患者中，33%存在残留疾病。

单因素分析显示，再次切除时残留疾病的存在与年龄、种族、绝经状态、最终切缘宽度、激素受体状态、肿瘤组织学、三阴疾病或血管淋巴浸润是否存在无任何显著关联。残留疾病与1个以上的2 mm以下切缘存在关联，但不显著。

中位随访43个月(范围0~140个月)发现，保乳治疗患者和乳房切除术患者的5年局部复发率分别为1.9%和1.1%。未接受再次切除的保乳治疗患者的5年局部复发率为1.8%，而需再次切除者的5年局部复发率为4.3%，改为乳房切除术的患者的5年局部复发率为0%。

接受再次切除的保乳治疗患者的局部复发率趋于增高，但不显著，不过在排除转为乳房切除术的患者后，观察到显著增高，与未进行再次切除的患者相比，危险比为2.56(P=0.04)。

在第二项研究中，德克萨斯大学M.D.安德森癌症中心的Elizabeth FitzSullivan博士对1996~2009年810例接受乳房切除术的DCIS女性患者进行了回顾，分析了组织学切缘的最终宽度，无病切缘定义为≥3 mm。

Elizabeth FitzSullivan博士

总体而言，4例患者存在阳性切缘，59例的切缘≤1 mm，35例的切缘为1.1~2.9 mm。

多因素分析显示，临近或阳性切缘的独立预测因素是病理肿瘤大小≥1.5 cm[比值比(OR)=5.11；P=0.001]、多中心疾病(OR=5.44；P=0.026)和存在坏死(OR=2.5；P=0.003)。然而，年龄、绝经后状态、保留皮肤乳房切除术和即刻乳房再造均与临近或阳性切缘无显著关联。

在7例进行乳房切除术后放疗的患者中，无1例出现局部区域复发。在未接受术后放疗的803例患者中，10年LRR率为1%，包括7例浸润性疾病和1例DICS。5例患者接受手术治疗，其余3例未接受进一步治疗。

根据切缘状态对局部复发率进行分层发现，切缘≤1 mm的患者的10年LRR率为5%，而切缘1.1~2.9 mm的患者为3.6%，具有无病切缘的患者仅为0.07%(P＜0.001)。两组切缘狭窄的患者的LRR率无差异。

在546例对侧乳房完整的患者中，对侧乳腺癌的10年发生率为6.4%。

单因素分析显示，LRR的显著预测因素包括切缘状态(P=0.002)、多中心疾病(P=0.005)和坏死(P=0.005)。然而，多因素分析显示，仅切缘状态是LRR的显著预测因素，HR为8.0(P=0.006)。

研究者表示，接受乳房切除术的具有临近手术切缘的DCIS患者的LRR率低于对侧乳腺癌发生率，表明不需要在乳房切除术后常规进行放疗，而应仅对具有手术无法切除的临近或阳性切缘的患者进行术后常规放疗。

上述两项研究均由内部资金支持。Garvey博士和FitzSullivan博士均声明无经济利益冲突。

爱思唯尔版权所有  未经授权请勿转载

By: NEIL OSTERWEIL, Oncology Practice

NATIONAL HARBOR, MD. – Small surgical margins can mean big trouble for patients with breast cancer, said investigators at the annual Society of Surgical Oncology Cancer Symposium.

A retrospective study of outcomes for 2,377 women who underwent either breast-conserving therapy or mastectomy revealed that margins less than 2 mm resulted in a substantial risk of residual disease for all patients, reported Dr. Erin Garvey, a general surgery resident at Mayo Clinic Arizona in Phoenix.
 
"A policy of re-excision for margins less than 2 mm, coupled with a standardized multidisciplinary approach to breast cancer surgery, results in excellent re-excision and 5-year local recurrence rates. The local recurrence rate is higher, however, for those patients who complete breast-conserving therapy, thus warranting appropriate patient counseling regarding re-excision options and long-term outcome expectations," she said.

In a separate study, investigators from the University of Texas M.D. Anderson Cancer Center, Houston, reported 10-year follow-up data for women who opted for mastectomy to treat ductal carcinoma in situ (DCIS). They found that the incidence of local-regional recurrence (LRR) increased as the surgical margins shrank, and that close margins were the only independent predictor of LRR, reported Dr. Elizabeth FitzSullivan, a surgery fellow at M.D. Anderson.

"However, the local-regional recurrence rate in these patients is so low that routine postmastectomy radiation therapy is not warranted," she said.

No accord on margins

Despite multiple studies and meta-analyses, there is no standard for acceptable margin width in breast cancer, and surveys of both surgeons and radiation oncologists have shown wide variations in preferred margin widths, Dr. Garvey said.

Her group hypothesized that patients with invasive ductal carcinoma without an extensive in situ component who had surgical margins of at least 1 mm would have no evidence of residual disease on re-excision.

To test the idea, they took a retrospective look at records from a prospective database on 2,377 patients who underwent a total of 2,520 procedures from January 2000 through May 2012.

Of this group, 1,498 (63%) underwent lumpectomy, and 180 (12%) required re-excision surgery: 10% who had breast-conserving surgery alone, and 2% whose surgeries were converted to mastectomies. Of the 158 patients who had completed breast-conserving therapy following re-excision, 50 (32%) had residual disease, as did 20 of the 27 patients whose procedures were converted to mastectomies.

Of the 37% (879) who had up-front mastectomies, 2% (19) had re-excision, and of this group, 5 patients had residual disease.

In all, 40% of patients with positive margins had residual disease, compared with 38% of those with margins from 0.1 to 0.9 mm, and 33% for those with margins from 1.0 to 1.9 mm.

In univariate analysis, the presence of residual disease on re-excision did not show any significant association with age, race, menopausal status, width of the closest final margin, hormone receptor status, tumor histology, triple-negative disease, or the presence of angiolymphatic invasion. There was a trend, albeit nonsignificant, toward an association between residual disease and more than one margin narrower than 2 mm, Dr. Garvey noted.

At a median follow-up of 43 months (range, 0-140 months), 5-year local recurrence rates were 1.9% for patients who had breast-conserving therapy, and 1.1% for those who had mastectomy.

Patients who underwent breast-conserving therapy without re-excision had a 5-year local recurrence rate of 1.8%, compared with 4.3% for those who required re-excision, and 0% for those whose procedures were converted to mastectomy.

There was a nonsignificant trend toward higher local recurrence rates for breast-conserving therapy in patients who had re-excisions, which became significant when those patients who had conversion to mastectomy were excluded, with a hazard ratio compared with no re-excision of 2.56 (P = .04).

Narrower margins, larger risk

Dr. FitzSullivan and her M.D. Anderson colleagues reviewed the records of 810 women treated with mastectomy for DCIS from 1996 to 2009. They looked at the final width of histologic margins, defining disease-free margins as those of 3 mm or greater.

In all, 4 patients had positive margins, 59 had margins of 1 mm or smaller, and 35 had margins from 1.1 to 2.9 mm.

In multivariate analysis, independent predictors of close or positive margins were pathologic tumor size of 1.5 cm or greater (odds ratio, 5.11; P = .001), multicentric disease (OR, 5.44; P = .026), and the presence of necrosis (OR, 2.5; P = .003). Neither age, postmenopausal status, skin-sparing mastectomy, nor immediate breast reconstruction were significantly associated with close or positive margins, however.

None of seven patients who underwent postmastectomy radiotherapy had local-regional recurrences. Of the 803 patients who did not receive postsurgery radiation, 10-year LRR rates were 1%, consisting of 7 cases of invasive disease and 1 of DICS. Five patients had surgical management, and the remaining 3 had no further treatment.

When the researchers stratified the local recurrence rates by margin status, they saw that 5% of patients with margins of 1 mm or smaller had LRRs within 10 years, as did 3.6% of those with margins from 1.1 to 2.9 mm, compared with just 0.07% of those with disease-free margins (P less than .001). There was no difference in LRR between the two narrow-margin groups.

Among 546 patients with an intact contralateral breast, the 10-year rate of contralateral breast disease was 6.4%.

On univariate analysis, significant predictors of LRR included margin status (P = .002), multicentric disease (P = .005), and necrosis (P = .005). On multivariate analysis, however, only margin status remained significant, with an HR of 8.0 (P = .006).

Dr. FitzSullivan said that the low rate of LRR of DCIS treated with mastectomy and close surgical margins, compared with the rate of contralateral breast cancer, suggests that routine postmastectomy radiation therapy is not warranted, and should be reserved only for those patients with close or positive surgical margins that cannot be surgically excised.

Each study was internally funded. Dr. Garvey and Dr. FitzSullivan reported having no financial disclosures.