ASSO2013：预防性对侧乳房切除术无益生存反增加并发症

美国肿瘤外科学会(ASSO)年度癌症研讨会上公布的一项研究显示，尽管没有证据表明对侧预防性乳房切除术(CPM)对生存有益，但该手术的开展率仍在不断上升。据10所国家综合癌症网络中心(NCCN)的其中一所报道，从1998年至2007年，分别有21%的原位管癌(DCIS)和17%的I-III期乳腺癌患者在单侧乳房切除术后1年内进行了对侧预防性乳房切除术(CPM)。

俄亥俄州立大学综合癌症中心的外科教授William E. Carson III博士及其同事对I-III期浸润性乳腺癌患者总生存期的分析显示，与仅接受单侧乳腺癌切除术的患者相比，接受CPM术的患者其总生存期存在非常显著的差异，这与患者是否接受新辅助化疗无关。另一项芝加哥大学外科医生Megan Miller完成的研究显示，与单侧乳房切除术相比，CPM导致并发症发生率增加，包括需要再手术或再入院治疗的主要并发症的风险同样增加。“CPM患者发生任意并发症的机率是单侧乳房切除术后患者的1.5倍，而重要并发症的发生率则是后者的2.6倍。”她在美国肿瘤外科学会(ASSO)年度癌症研讨会上说。CPM患者约40%的并发症发生于无癌灶的一侧。

SSO立场声明

Carson医生指出，外科肿瘤学会（SSO）2007年立场声明称，目前或先前诊断的患者中对于那些整形如对称性或平衡性存在问题或监护困难的患者，或可推荐CPM以减少风险。两项研究利用流行病学和最终结果监测(Surveillance, Epidemiology and End Results, SEER)数据(Tuttle et al. [J. Clin. Oncology 2009;27:1362-7]); Bedrosian et al. [J. Natl. Cancer Inst. 2010;102:401-9])，一项研究利用本研究的数据(Jones et al. [Ann. Surg. Oncol. 2009;16:2691-6])，其结果显示在过去的10年间，CPM开展率增加了10%。学历越高、越年轻的女性越倾向于选择CPM。

为了考察NCCN中心是否也有这样的趋势，Carson III博士及其同事对1998~2007年间在国家综合癌症网络(NCCN)旗下10个中心接受单侧乳房切除术的1,309例导管原位癌(DCIS)女性患者和7,044例Ⅰ~Ⅲ期浸润性乳腺癌女性患者的数据进行了分析。两组的中位随访时间超过4年。DCIS组和Ⅰ~Ⅲ浸润性乳腺癌组分别有272例(21%)和1,199例(17%)患者在接受单侧乳房切除术后的1年内接受了CPM。

多因素分析显示，能够预测患者接受CPM的可能性的显著因素包括年龄＜50岁、白人、接受MRI检测，以及肿瘤≤1 cm。在浸润性乳腺癌女性患者中，教育程度、淋巴结阴性状态和无即刻乳房再造也是CPM的显著预测因素(均P＜0.0001)。

不同中心的CPM开展率不同，在DCIS患者中的开展率为8.2%~34.7%，在Ⅰ~Ⅲ期浸润性乳腺癌患者中的开展率为3.6%~30.8%。其他研究显示，DCIS患者的CPM开展率从1998年的15%增至2007年的27%，浸润性乳腺癌患者的CPM开展率从8%增至26%。在50岁以下患者中观察到的增幅最显著。

校正年龄、人种、肿瘤大小、淋巴结状态、肿瘤级别、组织学和治疗，进行多因素Cox回归分析发现，与单纯单侧乳房切除术相比，单侧乳房切除术加CPM在总生存方面无优势。

并发症

芝加哥大学的Megan Miller博士及其同事回顾性分析了2009年1月~2012年3月在该中心接受单侧乳房切除术(391例)或CPM(209例)的600例患者的数据。观察指标是严重并发症和轻微发症。严重并发症包括需要再次手术的血清肿或血肿、需要住院的感染、全乳头或皮瓣坏死、以及需要输血的出血。轻微并发症包括需要抽吸的血清肿及血肿、需要口服抗生素的感染、部分乳头或皮瓣坏死、轻微出血和伤口愈合延迟。

单侧乳房切除术组和CPM组任何并发症的发生率分别为29%和42%(P＜0.001)，严重并发症的发生率分别为4.1%和14%( P＜0.001)，轻微并发症的发生率均为15%，多重严重并发症的发生率分别为4.9%和9.1%(P=0.043)。在CPM组中，40%的并发症发生于CPM术侧。校正年龄、体重指数、糖尿病、既往放射、吸烟史和再造类型，进行多因素分析发现，CPM患者发生任何并发症的比值比(OR)为1.5(P=0.029)，发生严重并发症的OR为2.6(P=0.007)。

Miller医生说，我们相信考虑CPM的患者有必要意识到上述风险，肯定还需要更多的关于患者决策途径和参与决策制定的研究。这两项研究均由内部资金支持。Carson博士是NCCN董事会成员。Miller博士声明无经济利益冲突。

与乳房切除术相关的拓展阅读：

• 乳腺癌保乳术后近距离放疗乳房切除术风险加倍
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Contralateral prophylactic mastectomy adds complications
NATIONAL HARBOR, MD. – The rate of contralateral prophylactic mastectomies is rising, even though there is no evidence for a survival benefit.
From 1998 through 2007, contralateral prophylactic mastectomies (CPM) were performed within 1 year of unilateral mastectomies in 21% of those with ductal carcinoma in situ (DCIS) and in 17% of those with stage I-III breast cancer who were treated at one of 10 National Comprehensive Cancer Network (NCCN) centers.
But in an analysis of overall survival for patients with stages I-III invasive breast cancer, there was so significant difference in overall survival for patients who underwent a CPM, compared with those who underwent only unilateral mastectomy, regardless of whether they had received neoadjuvant chemotherapy, reported Dr. William E. Carson III, professor of surgery at the Ohio State University Comprehensive Cancer Center in Columbus.
In addition, CPMs are associated with a significantly greater risk of complications than unilateral mastectomies, including increased risk for major complications requiring reoperation and rehospitalization, said Dr. Megan Miller, a surgery resident at the University of Chicago, Illinois.
"CPM patients are 1.5 times more likely to have any complication, and 2.6 times more likely to have a major complication than unilateral mastectomy patients," she said at the annual Society of Surgical Oncology Cancer Symposium.
Among patients who underwent CPM, almost 40% of the complications occurred on the side of the body without cancer, she noted.
SSO position statement
A 2007 position statement from the Society of Surgical Oncology (SSO) states that in patients with a current or prior diagnosis, CPM may be indicated for risk reduction in cases where surveillance is difficult or for reconstructive issues such as symmetry and balance, Dr. Carson noted.
Two studies using Surveillance, Epidemiology, and End Results (SEER) data (Tuttle et al. [J. Clin. Oncology 2009;27:1362-7]); Bedrosian et al. [J. Natl. Cancer Inst. 2010;102:401-9]) and one from his own center (Jones et al. [Ann. Surg. Oncol. 2009;16:2691-6]) showed about a 10% increase in the rate of CPM over a decade. Younger women with higher levels of education were more likely to seek CPM.
To see whether this trend extended to NCCN centers, Dr. Carson and his colleagues reviewed data on 1,309 women with DCIS, and 7,044 with stage I-III breast cancer who underwent unilateral mastectomy from 1998 through 2007 at one of 10 designated centers.
In all, 273 of the women diagnosed with DCIS (21%) had a contralateral prophylactic mastectomy, as did 1,199 (17%) of the women with a diagnosis of stage I-III invasive disease. Median follow-up was more than 4 years for both groups.
In a multivariate analysis, factors that significantly predicted the likelihood of CPM included age younger than 50 years, Caucasian race, MRI as the method of detection, and tumor size of 1 cm or smaller. In women with invasive disease, years of education, node-negative status, and no immediate reconstruction were also significant predictors of CPM (P less than .0001 for all variables).
Use of CPM varied widely by institution from 8.2%-34.7% of women with DCIS, and from 3.6%-30.8% of patients with stage I-III disease. As other studies have shown, the use of CPM increased over time, from 15% for DCIS in 1998 to 27% in 2007. For patients with invasive breast cancer, the respective increase was from 8% to 26%. The most pronounced increases were among patients younger than 50 years, Dr. Carson noted.
When they looked at overall survival in a multivariate Cox regression model adjusted for age, race, tumor size, nodal status, tumor grade, histology, and treatment, they found that there was no significant survival advantage for unilateral mastectomy plus CPM, compared with unilateral mastectomy alone.
Complications, complications
Dr. Miller and her colleagues retrospectively reviewed 600 patients who underwent either unilateral mastectomy (391) or CPM (209) at their center from January 2009 through March 2012. They looked at major complications such as seroma or hematoma requiring reoperations, infections requiring hospital admission, total nipple or flap necrosis, and bleeding requiring transfusion; and minor complications such as seromas and hematomas requiring aspiration, infections requiring oral antibiotics, partial nipple or flap necrosis, minor bleeding, and delayed wound healing.
The percentage of patients experiencing any complications was 29% for patients who had a unilateral mastectomy, compared with 42% of those who underwent CPM (P less than .001). Major complications occurred in 4.1% and 14%, respectively (P less than .001). Rates of minor complications were identical between the groups, at 15% each.
Multiple major complications were seen in 4.9% of unilateral patients, compared with 9.1% of CPM patients (P = .043).
Among the CPM patients, 40% of complications occurred on the CPM side.
In a multivariate analysis controlling for age, body mass index, diabetes, previous radiation, smoking history and reconstruction type, CPM was associated with an odds ratio for any complication of 1.5 (P = .029) and 2.6 for major complications (P = .007).
"We believe that patients considering CPM should be made aware of these risks, and certainly more research is needed on patient decision pathways and shared decision making," Dr. Miller said.
Both Dr. Carson’s and Dr. Miller’s studies were internally funded. Dr. Carson disclosed serving on the NCCN Board of Directors. Dr. Miller reported having no financial disclosures.