Magnoni Francesca, Corso Giovanni, Maisonneuve Patrick, Bianchi Beatrice, Accardo Giuseppe, Sangalli Claudia, Massari Giulia, Rotili Anna, Nicosia Luca, Pesapane Filippo, Montagna Emilia, Mazzarol Giovanni, Galimberti Viviana, Veronesi Paolo, Curigliano Giuseppe
Division of Breast Surgery, IEO European Institute of Oncology, IRCCS, Milan, Italy.
European Cancer Prevention Organization (ECP), 20141, Milan, Italy.
EClinicalMedicine. 2024 Mar 20;71:102552. doi: 10.1016/j.eclinm.2024.102552. eCollection 2024 May.
Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria.
We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score.
A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population.
Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment.
Umberto Veronesi Foundation.
阿贝西利目前被批准用于高危、淋巴结（LN）阳性、激素受体（HR）阳性乳腺癌（BC）的辅助治疗。在现实世界中，潜在符合阿贝西利辅助治疗条件的患者的临床病理特征仍有待确定。关于浸润性小叶癌（ILC）和浸润性导管癌（IDC）的生物学行为和长期预后存在相互矛盾的数据。在我们的研究中，我们根据MonarchE试验纳入标准，回顾性评估了选定的具有高危特征的ILC与IDC相比的真实世界数据和长期预后。
我们确定了2000年至2008年在欧洲肿瘤研究所接受首次原发性、非转移性、HR阳性、HER2阴性乳腺癌手术的15071例患者。11981例（79.5%）患者为IDC，1524例（10.1%）为ILC。其余1566例患者（10.4%）患有导管和小叶混合型乳腺癌或其他组织学乳腺癌亚型。根据MonarchE研究的纳入标准，我们根据阳性淋巴结数量多、肿瘤体积大或通过肿瘤分级或生物标志物测量的高细胞增殖，确定了两个高危组。患者通过倾向评分进行匹配。
共有2872例（21.3%）患者被选为临床高危患者，包括361/1524例ILC（23.7%）和2511/11981例IDC（21%）。322例高危ILC与相似的高危IDC进行了匹配。生存的中位随访时间为13.2年。在匹配组中，两个组织学组之间的无侵袭性疾病生存期（IDFS）（对数秩P = 0.09）和总生存期（OS）（对数秩P = 0.48）无统计学显著差异。对于IDC患者，5年和10年IDFS率（95%CI）分别为77.7%（72.9 - 82.2）和57.3%（51.7 - 63.1），而ILC患者的5年和10年IDFS率分别为75.5%（70.6 - 80.2）和50.7%（45.0 - 56.6）。IDC队列的5年和10年远处无复发生存期（DRFS）率分别为80%（75.3 - 84.2）和65.3%（59.8 - 70.7），而ILC队列的5年和10年DRFS率分别为78.7%（74.0 - 83.1）和61.5%（55.9 - 67.1）。这些数据与MonarchE对照组最近的疗效结果相符。ILC组（n = 17）发生腋窝复发的患者比IDC组（n = 10）多。在多变量分析中，按特定临床特征分层，年龄<35岁、pT2 - 3、腋窝有超过10个阳性腋窝淋巴结受累被发现是总体匹配高危人群中不良IDFS和OS的预测因素。
这项匹配队列研究的结果报告显示与MonarchE试验报告的对照组总体IDFS和DRFS率相比，高危HR阳性早期乳腺癌的IDFS和DRFS率相似。我们的研究表明，除了组织学亚型之外，长期预后状态也具有一致性。这些数据支持对这两种不同组织学类型的高危特征患者采取强化治疗策略。在我们的数据集中，约21%的高危HR阳性早期乳腺癌患者可能符合阿贝西利辅助治疗条件。
翁贝托·韦罗内西基金会
