Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial.
Effect of body mass index on response to neo-adjuvant therapy in HER2-positive breast cancer: an exploratory analysis of the NeoALTTO trial.
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体重指数对HER2阳性乳腺癌中对新辅助治疗的反应的影响：Neoaltto试验的探索性分析。
DOI：
10.1186/s13058-020-01356-w
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发表时间：
2020-10-27
期刊：
影响因子：
--
通讯作者：
de Azambuja E
中科院分区：
文献类型：
--
作者：
Di Cosimo S;Porcu L;Agbor-Tarh D;Cinieri S;Franzoi MA;De Santis MC;Saura C;Huober J;Fumagalli D;Izquierdo M;Piccart M;Daidone MG;de Azambuja E
肥胖是乳腺癌（BC）发展、复发和死亡的危险因素。有鉴于此，我们旨在研究NeoALTTO试验中接受抗HER 2治疗的BC患者中肥胖的临床价值，该试验将455例患者随机分配至新辅助拉帕替尼、曲妥珠单抗或其联合治疗加紫杉醇组。根据基础体重指数（BMI）将患者分为体重不足（< 18.5 kg/m2）、正常（≥ 18.5; < 25 kg/m2）、超重（≥ 25; < 30 kg/m2）和肥胖（≥ 30 kg/m2）WHO类别。使用BMI作为分类变量进行单变量和多变量logistic回归分析。病理完全缓解（pCR）和无事件生存期（EFS）分别是NeoALTTO的主要和次要结局。在分析的454例患者中，分别有14例（3%）、220例（48%）、137例（30%）和83例（18%）被归类为体重不足、体重正常、超重和肥胖; 231例（51%）和223例（49%）原发性肿瘤为激素受体（HR）阳性和HR阴性; 160例（35%）达到pCR。在总体患者人群中，未发现BMI组与pCR之间存在关联，因为我们报告体重不足、正常体重、超重和肥胖病例的pCR率分别为57.1%、35%、30.7%和39.8%。相反，在HR阳性肿瘤中，超重或肥胖通常与实现pCR的可能性降低相关，而与其他临床变量无关，包括计划的手术、淋巴结状态和肿瘤大小（比值比[OR] = 0.55，95%CI 0.30-1.01，与正常或体重不足相比; p = 0.053）;值得注意的是，在HR阴性病例中未观察到BMI对pCR的差异性影响（与正常或体重不足者相比，OR = 1.30，95%CI 0.76-2.23; p = 0.331），导致BMI和HR状态之间存在统计学显著的相互作用（p = 0.036）。无论是在总体还是HR阳性人群中，BMI和EFS之间都没有相关性，但这项分析的效力不足。基线时超重或肥胖且HR阳性原发性BC的NeoALTTO患者在新辅助抗HER 2治疗后似乎不太可能实现pCR。这一发现为未来针对HER 2/HR信号传导和代谢之间相互作用的研究铺平了道路。
Obesity is a risk factor for breast cancer (BC) development, recurrence, and death. In view of this, we aimed to investigate the clinical value of obesity in BC patients treated with anti-HER2 therapies in the NeoALTTO trial, which randomized 455 patients to neo-adjuvant lapatinib, trastuzumab, or their combination plus paclitaxel. Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m2), normal (≥ 18.5; < 25 kg/m2), overweight (≥ 25; < 30 kg/m2), and obese (≥ 30 kg/m2) WHO categories. Univariate and multivariate logistic regression analyses were performed using BMI as a categorical variable. Pathological complete response (pCR) and event-free survival (EFS) were the NeoALTTO primary and secondary outcomes, respectively. Among 454 patients analyzed, 14 (3%), 220 (48%), 137 (30%), and 83 (18%) were classified as underweight, normal weight, overweight, and obese, respectively; 231 (51%) and 223 (49%) had hormone receptor (HR)-positive and HR-negative primary tumors; 160 (35%) achieved pCR. In the overall patient population, no association was found between BMI groups and pCR, as we reported pCR rates of 57.1%, 35%, 30.7%, and 39.8% in underweight, normal weight, overweight, and obese cases, respectively. In contrast, in HR-positive tumors, overweight or obesity was generally associated with decreased likelihood of achieving a pCR independently of other clinical variables, including planned surgery, nodal status, and tumor size (odds ratio [OR] = 0.55, 95%CI 0.30–1.01, as compared to normal or underweight; p = 0.053); notably, no differential effect of BMI with respect to pCR was observed in HR-negative cases (odds ratio [OR] = 1.30, 95%CI 0.76–2.23, as compared to normal or underweight; p = 0.331), resulting in a statistically significant interaction between BMI and HR status (p = 0.036). There was no association between BMI and EFS neither in the overall nor in the HR-positive population, but this analysis was under-powered. NeoALTTO patients overweight or obese at baseline and with HR-positive primary BC appeared less likely to achieve pCR after neo-adjuvant anti-HER2 therapies. This finding paves the way to future research in targeting the interplay between HER2/HR signaling and metabolism.
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DOI：
10.1093/annonc/mdu042
发表时间：
2014-10
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Chan DSM;Vieira AR;Aune D;Bandera EV;Greenwood DC;McTiernan A;Navarro Rosenblatt D;Thune I;Vieira R;Norat T
通讯作者：
Norat T
影响因子：
11.5
作者：
Bardia, Aditya;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
3.8
作者：
Fontanella, Caterina;Lederer, Bianca;Loibl, Sibylle
通讯作者：
Loibl, Sibylle
影响因子：
45.3
作者：
Litton, Jennifer K.;Gonzalez-Angulo, Ana M.;Brewster, Abenaa M.
通讯作者：
Brewster, Abenaa M.
影响因子：
5.2
作者：
Salisbury TB;Tomblin JK
通讯作者：
Tomblin JK