Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, National Standardization Center for Breast Cancer Diagnosis and Treatment, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, People's Republic of China.
Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China.
Oncologist. 2021 Feb;26(2):e241-e250. doi: 10.1002/onco.13567. Epub 2020 Nov 3.
Small-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease.
Data between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size.
We identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did.
Patients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients.
This study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.
小尺寸的原发肿瘤并不总是预示着更好的预后。我们假设，广泛淋巴结转移的非常小的原发性乳腺肿瘤在 IV 期疾病中代表了侵袭性的生物学行为。
回顾性地从监测、流行病学和最终结果数据库中检索了 2010 年至 2015 年的数据，纳入标准为女性、单侧、转移性和 T1/2 浸润性导管癌。主要研究变量包括 T 分期、N 分期、分级、转移部位、受累部位数量、雌激素受体状态、孕激素受体状态和人表皮生长因子受体 2 状态。使用 Kaplan-Meier 和调整后的 Cox 比例风险模型及交互项。根据肿瘤大小检查 1、2 和 3 年乳腺癌特异性死亡率（BCSM）。
我们确定了 5340 名符合条件的乳腺癌患者。在多变量分析中，种族、年龄、分级、分子亚型、手术、脑转移和肝转移被发现与 BCSM 独立相关。对于 T1 肿瘤，N0、N1 和 N2+组的 BCSM 相同。在小于 50mm 的肿瘤中，1、2 和 3 年 BCSM 并未随着肿瘤大小的减小而降低。对于三阴性乳腺癌（TNBC），T1a/T1bN2+组的 BCSM 明显差于任何其他组。
IV 期癌症患者的小尺寸肿瘤可能具有与大尺寸肿瘤一样高的 BCSM。在 TNBC 中，伴有严重淋巴结受累的非常小的肿瘤与最差的 BCSM 相关。需要继续努力进一步研究 Ta1/T1bN2+M1 TNBC 并为受影响的患者制定个体化治疗方案。
本研究表明，对于 IV 期乳腺癌，较小的原发肿瘤并不总是与更好的乳腺癌特异性死亡率相关。本研究表明，广泛区域淋巴结受累的非常小的三阴性乳腺癌（TNBC）可能是生物学侵袭性疾病的代表。由于 T1a/T1bN2+TNBC 的预后较差，可能迫切需要为受影响的患者提供更个体化的治疗。未来的相关研究应侧重于导致 Ta1/T1bN2+TNBC 生物学行为差异的遗传和分子差异。阐明非常小的原发性 TNBC 与转移到淋巴结和远处部位的生长之间的调节机制将在开发靶向治疗中发挥重要作用。
