Background The diagnosis of mixed invasive ductal and lobular carcinoma (IDC‐L) in clinical practice is often associated with uncertainty related to its prognosis and response to systemic therapies. With the increasing recognition of invasive lobular carcinoma (ILC) as a distinct disease subtype, questions surrounding IDC‐L become even more relevant. In this study, we took advantage of a detailed clinical database to compare IDC‐L and ILC regarding clinicopathologic and treatment characteristics, prognostic power of histologic grade, and survival outcomes. Materials and Methods In this retrospective cohort study, we identified 811 patients diagnosed with early‐stage breast cancer with IDC‐L or ILC. Descriptive statistics were performed to compare baseline clinicopathologic characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan–Meier method and compared using the Cox proportional hazards model. Results Patients with ILC had more commonly multifocal disease, low to intermediate histologic grade, and HER2‐negative disease. Histologic grade was prognostic for patients with IDC‐L but had no significant discriminatory power in patients with ILC. Among postmenopausal women, those with IDC‐L had significantly better outcomes when compared with those with ILC: disease‐free survival (DFS) and overall survival (OS; adjusted hazard ratio HR, 0.54; 95% confidence interval CI 0.31–0.95). Finally, postmenopausal women treated with an aromatase inhibitor had more favorable DFS and OS than those treated with tamoxifen only (OS adjusted HR, 0.50; 95% CI, 0.29–0.87), which was similar for both histologic types (p = .212). Conclusion IDC‐L tumors have a better prognosis than ILC tumors, particularly among postmenopausal women. Histologic grade is an important prognostic factor in IDC‐L but not in ILC. Implications for Practice This study compared mixed invasive ductal and lobular carcinoma (IDC‐L) with invasive lobular carcinomas (ILCs) to assess the overall prognosis, the prognostic role of histologic grade, and response to systemic therapy. It was found that patients with IDC‐L tumors have a better prognosis than ILC, particularly among postmenopausal women, which may impact follow‐up strategies. Moreover, although histologic grade failed to stratify the risk of ILC, it showed an important prognostic power in IDC‐L, thus highlighting its clinical utility to guide treatment decisions of IDC‐L. Finally, the disease‐free survival advantage of adjuvant aromatase inhibitors over tamoxifen in ILC was consistent in IDC‐L. 摘要 背景。临床实践中混合浸润性导管和小叶癌 (IDC‐L) 的诊断通常与其预后和系统治疗反应相关的不确定性有关。随着人们日益认识到浸润性小叶癌 (ILC) 是一种独特的疾病亚型，围绕 IDC‐L 而产生的问题变得更加相关。在本次研究中，我们利用详细的临床数据库来比较 IDC‐L 和 ILC 的临床病理和治疗特征、组织学分级的预后能力以及生存预后。 材料和方法。在本次回顾性队列研究中，我们找到了 811 名被诊断为患有 IDC‐L 或 ILC 的早期乳腺癌患者。我们执行了描述性统计，以比较基线临床病理特征和治疗。随后，我们使用Kaplan–Meier分析方法对生存率进行了分析，并使用Cox比例风险模型进行了比较。 结果。ILC 患者患有更常见的多灶性疾病，组织学分级介于低级至中级之间，且为 HER2 阴性。组织学分级对 IDC‐L 患者而言是预后因素，但在 ILC 患者中没有显著的区分能力。在绝经后女性中，IDC‐L 患者的预后明显好于 ILC 患者:无病生存期 (DFS) 和总生存期 OS；校正风险比 (HR)，0.54；95% 置信区间 (CI) 0.31–0.95。最后，采用芳香化酶抑制剂治疗的绝经后女性在 DFS 和 OS 方面比仅采用他莫昔芬治疗的绝经后女性更好(OS 校正 HR，0.50；95% CI，0.29–0.87)，后一种治疗方式对这两种组织学类型而言效果相似 (p = 0.212)。 结论。IDC‐L 肿瘤的预后要好于 ILC 肿瘤，尤其在绝经后女性中更是如此。在 IDC‐L(而非 ILC)中，组织学分级是一个重要的预后因素。 实践意义:本研究将混合浸润性导管和小叶癌 (IDC‐L) 与浸润性小叶癌(ILC)进行对比，以评估总体预后、组织学分级的预后作用以及系统治疗的反应。研究发现，IDC‐L 肿瘤患者的预后要好于 ILC 患者，尤其在绝经后女性中更是如此，这可能会影响随访策略。此外，尽管组织学分级未能对 ILC 的风险进行分层，但是，它在 IDC‐L 中显示出重要的预后能力，因而突显其指导 IDC‐L 治疗决策的临床实用性。最后，辅助芳香化酶抑制剂在 ILC 中相对于他莫昔芬的无病生存期优势与在 IDC‐L 中的优势是一致的。 In this retrospective analysis, a large, detailed, and curated single center database was used to compare clinicopathologic features and outcomes between invasive lobular carcinoma and mixed invasive ductal and lobular carcinomas, focusing on the prognostic implications of histological grade and taking into consideration the differences in systemic therapies.