Holm Jonas Busk, Skovbjerg Stine Blaabjerg, Nielsen Hanne Melgaard, Christiansen Peer, Bruun Jens Meldgaard, Alsner Jan, Cronin-Fenton Deirdre, Borgquist Signe
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
Breast Cancer Res. 2025 Jul 11;27(1):130. doi: 10.1186/s13058-025-02083-w.
Obesity, defined as Body Mass Index (BMI) ≥ 30 kg/m, is associated with inferior breast cancer prognosis, but its effect on neoadjuvant chemotherapy response is uncertain. We hypothesized that obesity decreases the odds of pathological complete response (pCR) after neoadjuvant chemotherapy.
We assembled a cohort of women with breast cancer who underwent neoadjuvant chemotherapy and subsequent surgery between January 1, 2016, and December 31, 2020, in Denmark. Patients received six or eight series of EC-TAX (epirubicin, cyclophosphamide, and paclitaxel) based on disease stage. Trastuzumab and pertuzumab were also used for patients with HER2+ disease. BMI was assessed as a categorical variable (normal weight (BMI = 18.5-<25 kg/m), overweight (BMI = 25-<30 kg/m), and obesity (BMI ≥ 30 kg/m)) and as a continuous variable. We used multivariable logistic regression models to compute odds ratios (ORs) for pCR after neoadjuvant chemotherapy according to BMI groups, using normal weight as reference, and stratified by menopausal, estrogen receptor (ER), and HER2 status. We adjusted for age and menopausal status based on a directed acyclic graph.
Among 1819 patients, 417 had pCR. Patients with overweight (N = 585) or obesity (N = 450) had 22% and 27% lower odds, respectively, of pCR (OR=0.78 [95%CI = 0.60-1.00] and OR=0.73 [95%CI = 0.55-0.97]) compared with patients with normal weight (N = 784). In ER/HER2-stratified analyses, we observed lower pCR odds among women with obesity and HER2+ tumors (OR=0.72 [95%CI = 0.47-1.12]) compared with their normal weight counterparts, but no notable association appeared for ER+/HER2- (OR=0.97 [95%CI = 0.49-1.96]) and ER-/HER2- tumors (OR=0.88 [95%CI = 0.49-1.57]). In analyses stratified by menopausal status, obesity was associated with lower pCR odds among postmenopausal women (OR=0.62 [95%CI = 0.41-0.94]), and, to a lesser extent, premenopausal women (OR=0.86 [95%CI = 0.58-1.27]).
Our findings suggest that breast cancer patients with overweight or obesity have lower odds of pCR compared with patients with normal weight. As the results varied by ER and HER2 status, the observed association may depend on subtype. In summary, our results are consistent with earlier studies that propose BMI as a potential prognostic marker of pCR.
肥胖定义为体重指数（BMI）≥30kg/m²，与乳腺癌预后较差相关，但其对新辅助化疗反应的影响尚不确定。我们假设肥胖会降低新辅助化疗后病理完全缓解（pCR）的几率。
我们收集了2016年1月1日至2020年12月31日期间在丹麦接受新辅助化疗及后续手术的乳腺癌女性队列。患者根据疾病分期接受六或八个疗程的EC-TAX（表柔比星、环磷酰胺和紫杉醇）治疗。曲妥珠单抗和帕妥珠单抗也用于HER2阳性疾病患者。BMI被评估为分类变量（正常体重（BMI = 18.5 - <25kg/m²）、超重（BMI = 25 - <30kg/m²）和肥胖（BMI≥30kg/m²））以及连续变量。我们使用多变量逻辑回归模型，以正常体重为参照，根据BMI分组计算新辅助化疗后pCR的比值比（OR），并按绝经状态、雌激素受体（ER）和HER2状态进行分层。我们根据有向无环图对年龄和绝经状态进行了调整。
在1819例患者中，417例达到pCR。超重（N = 585）或肥胖（N = 450）患者的pCR几率分别比正常体重患者（N = 784）低22%和27%（OR = 0.78 [95%CI = 0.60 - 1.00]和OR = 0.73 [95%CI = 0.55 - 0.97]）。在ER/HER2分层分析中，我们观察到肥胖且HER2阳性肿瘤女性的pCR几率低于正常体重者（OR = 0.72 [95%CI = 0.47 - 1.12]），但ER阳性/HER2阴性（OR = 0.97 [95%CI = 0.49 - 1.96]）和ER阴性/HER2阴性肿瘤（OR = 0.88 [95%CI = 0.49 - 1.57]）未出现明显关联。在按绝经状态分层的分析中，肥胖与绝经后女性较低的pCR几率相关（OR = 0.62 [95%CI = 0.41 - 0.94]），在绝经前女性中相关性较小（OR = 0.86 [95%CI = 0.58 - 1.27]）。
我们的研究结果表明，与正常体重患者相比，超重或肥胖的乳腺癌患者pCR几率较低。由于结果因ER和HER2状态而异，观察到的关联可能取决于亚型。总之，我们的结果与早期将BMI作为pCR潜在预后标志物的研究一致。
