保乳治疗的生存获益优于乳房切除术

《癌症》杂志1月28日在线发表的一项研究显示，进行保乳治疗即乳房肿块切除术的Ⅰ期或Ⅱ期乳腺癌女性的全因死亡率比进行乳房切除术的女性低28%，并且乳腺癌死亡率比后者低16% (Cancer Jan. 28, 2013 [doi:10.1002/cncr.27795])。

在这项研究中，杜克大学综合癌症中心的E. Shelley Hwang博士及其同事回顾了1990年至2004年112,154例被诊断为新发单侧T1/T2Ⅰ期或Ⅱ期乳腺癌的女性患者的病历。大部分女性(61,771例)接受肿块切除术和放疗；其余女性接受无放疗的乳房切除术。中位随访时间为10年。两组有1/4的患者在诊断时的年龄小于50岁；另1/4为70~80岁；少数(6%)小于40岁。

保乳治疗率从1990~92年的37%增至2002~04年的62%，而乳房切除手术率呈下降趋势。中位肿瘤大小为1.5 cm；肿瘤越大的患者越倾向于接受乳房切除术。保乳治疗在不同年龄组中的应用率存在差异，肿瘤≤2 cm的年龄最小组和年龄最大组的保乳治疗率最低，肿瘤＞2 cm的患者保乳治疗率随年龄而降低。

随访期间共有31,416例患者死亡，其中39%的死因为乳腺癌；5年总生存率为89%。

为了进一步探索治疗与死亡之间的交互作用，研究者根据年龄和肿瘤特征将队列分成4组：≥50岁，激素受体(HR)阴性；≥50岁，HR阳性；＜50岁，HR阴性；＜50岁，HR阳性。结果显示，与乳房切除组相比，保乳治疗组HR阳性的≥50岁女性的生存获益最大[比值比(HR)=0.81]。HR阳性的50岁以下女性的获益最小(HR=0.93)，但仍具有统计学显著性。

研究者还对3年总生存和疾病特异性生存进行了评估。结果显示，保乳治疗组3年全因死亡率显著低于乳房切除组，这些原因包括心脏病(HR=0.51)、慢性肺病(HR=0.46)和脑血管疾病 (HR=0.64)。这些结果可能与基线疾病负担方面的一些差异相关。在全因死亡方面，乳房切除组女性在乳腺癌诊断3年内死亡的几率大于保乳治疗组。基于这些结果可合理推测，乳房切除组患者就诊时的非致死性合并症负担可能较大，并且这一因素可能影响了手术决策。但是，单纯这一因素不能解释校正年龄和肿瘤特征后在乳房切除组中观察到的较低疾病特异性生存。

研究者表示，从保乳治疗与生存之间的强烈相关性来看，保乳治疗与放疗联合应用时，生存方面的获益至少等同于或甚至优于乳房切除术。

该研究获美国国立癌症研究所资助。Hwang博士声明无经济利益冲突。

随刊述评：有趣且重要的研究

Hope S. Rugo博士

《肿瘤学报告》(Oncology Report)副主编Hope S. Rugo博士在评价该研究时指出，这是一项有趣且重要的研究，但论文中未提及系统治疗，而系统治疗对乳腺癌特异性生存具有重大影响。由于混杂因素可能产生偏倚，因此需谨慎解读该研究观察到的生存获益。

虽然该研究存在上述缺陷，但是其结果具有重要意义。目前，乳房切除术的获益明显被过分渲染，在保乳手术可获得同等预后的情况下，患者往往还是倾向于选择乳房切除术。患者通常认为手术越彻底预后就越好。

在这方面，需要加强对患者的教育，而这需要外科医生和肿瘤医生的积极参与。保乳治疗不仅可显著改善乳腺癌女性患者的生存质量，而且不会有损美观。对于认为乳房切除术是比保乳治疗更简单易行的早期乳腺癌治疗方案的医生而言，该研究结果具有消除这种错误观念的提醒作用。

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By: MICHELE G. SULLIVAN, Internal Medicine News Digital Network

Women who underwent lumpectomy for stage I or II breast cancer were 28% less likely to die from any cause and up to 16% less likely to die from breast cancer, compared with women who underwent mastectomy, Dr. E. Shelley Hwang and her colleagues reported Jan. 28 in the online issue of Cancer.

The 3-year disease-specific survival benefit for breast-conserving therapy (BCT) was most pronounced for chronic respiratory disease, for which lumpectomy was associated with a 54% decreased risk of death; heart disease, with a 49% decreased risk; and cerebrovascular disease, with a decreased risk of 36%.

The survival benefit varied with age, tumor size, and hormone receptor status but was significant in every subgroup, Dr. Hwang and her colleagues wrote (Cancer Jan. 28, 2013 [doi:10.1002/cncr.27795]).

"Our findings have important implications for understanding the overall benefit of BCT at the population level," wrote Dr. Hwang of the Duke University Comprehensive Cancer Center, Durham, N.C., and her coauthors. "These results provide confidence in the efficacy of BCT even among younger patients with HR-negative disease thought to be at relatively higher risk for local failure."

The team reviewed the records of 112,154 women who were treated for a new, unilateral T1/T2 stage I or II breast cancer diagnosed from 1990 to 2004. Most of these women (61,771) underwent a lumpectomy and radiation; the remainder underwent mastectomy without radiation. They were followed for a median of 10 years.

About a quarter of each group was younger than 50 years when diagnosed; another quarter was aged 70-80 years. A small portion (6%) was younger than 40 years.

Surgical approach evolved over the study period. Breast-conserving therapy increased from 37% in 1990-92 to 62% by 2002-04, while the rate of mastectomies declined.

The median tumor size was 1.5 cm; patients with larger tumors were more likely to have mastectomies. "Interestingly, the use of BCT varied by age even among tumors [smaller than and equal to] 2 cm where the youngest and oldest age groups had the lowest BCT rate. In [tumors larger than] 2 cm, BCT rate declined by age," Dr. Hwang and her associates said.

Over the follow-up period, there were 31,416 deaths; 39% of these were caused by breast cancer; 5-year overall survival was 89%.

To further explore the treatment-mortality interaction, the investigators divided the cohort into four groups according to age and tumor characteristics:

· 50 years or older, hormone receptor negative.

· 50 years or older, hormone receptor negative.

· Younger than 50 years, hormone receptor positive.

· Younger than 50 years, hormone receptor positive.

Women 50 years and older with HR-positive tumors who had BCT experienced the greatest survival benefit, compared with mastectomy patients (hazard ratio, 0.81). Women younger than 50 years with HR- positive tumors experienced the smallest benefit (HR, 0.93), but one which was still statistically significant.

The investigators also looked at 3-year overall and disease-specific survival. "Notably, BCT was associated with significantly lower 3-year mortality rates from all causes," including heart disease (HR, 0.51), chronic respiratory disease (HR, 0.46), and cerebrovascular disease (HR, 0.64).

The findings align with those of randomized trials showing the benefits of BCT, the authors noted.

"Despite this, recent studies have shown an increased rate of mastectomy for patient subgroups including younger women with early-stage tumors, many of which would have presumably been amenable to BCT," they wrote. This could be the result of a perception that women with unfavorable characteristics, like younger age and high-risk tumors, don’t do as well with BCT.

The investigators noted that some differences in disease burden at baseline could have contributed to the findings.

"Interestingly, for every cause of mortality that we evaluated, women who had mastectomy were more likely to die within 3 years of their breast cancer diagnosis than women who chose BCT. Based on these findings, it is reasonable to infer that the mastectomy group was likely to have a greater burden of nonfatal comorbidities at presentation, and that this factor may well have influenced surgical decision-making. Nevertheless, this factor alone cannot account for why women with mastectomy had lower [disease specific survival] after adjusting for age and tumor characteristics," Dr. Hwang and her associates said.

Based on the strong associations with survival, "these findings support the notion that BCT, when combined with radiation, confers at least equivalent and perhaps even superior survival to mastectomy as definitive breast cancer treatment," they said.

The National Cancer Institute funded the study. Dr. Hwang had no financial disclosures.

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Interesting and important article

This article is interesting and important, but I don’t see any mention of systemic therapy, which has a huge impact on breast cancer–specific survival. Confounding factors could have created bias in this registry analysis that makes interpretation of improved survival impossible.

Having said that, I believe this is an important publication. The benefits of mastectomy are clearly overemphasized, and mastectomy is used in many situations where breast-conserving surgery will result in at least an identical outcome. Patients often understand that their outcome will be improved if more surgery is done, or if they remove the offending breast.

Education for patients in this regard is critical. Surgeons and medical oncologists are critical components of a change in practice – a change that has the potential to significantly improve quality of life and cosmetic outcome for women with breast cancer, representing over 200,000 patients per year in the United States. Hopefully, data such as these will disabuse practitioners of the all-too-common approach that mastectomy is an easier, simpler solution than breast-conserving surgery when managing early-stage breast cancer.

Hope S. Rugo, M.D., associate editor of The Oncology Report, is professor of medicine and director of breast oncology and clinical trials education at the comprehensive cancer center of the University of California, San Francisco.