Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057, New York, NY, 10029 , USA.
Department of Oncology, The Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing, China.
Breast Cancer. 2021 Nov;28(6):1235-1242. doi: 10.1007/s12282-021-01261-w. Epub 2021 May 18.
We evaluated the prognostic ability of immunohistochemistry (IHC)-based vs. PAM50-based subtypes for breast cancer mortality in a population-based study of breast cancer.
We included a total of 463 breast cancer cases from the population-based Long Island Breast Cancer Study Project (LIBCSP). IHC-based markers were abstracted from the medical records, while the PAM50-based intrinsic subtypes were assessed from tumor tissues using NanoString nCounter Analysis System. Cox proportional hazards models were used to estimate hazards ratios (HRs) for breast cancer-specific mortality associated with subtypes.
For IHC-based hormone receptor-positive (HR+) tumors (n = 361), 68.7% were classified as luminal subtypes by PAM50; for HR- tumors (n = 102), 95.1% were classified as non-luminal subtypes. Compared to HR+/HER2- subtype, HR- patients had significantly higher breast cancer mortality (HR-/HER2+: HR = 2.84, 95% CI = 1.58-5.11; triple-negative breast cancer: HR = 2.42, 95% CI = 1.44-4.06). Compared to luminal A, a higher mortality rate was observed for all other PAM50-based subtypes: luminal B (HR = 4.03, 95% CI = 1.97-8.22), HER2-enriched (HR = 6.82, 95% CI = 3.29-14.14) and basal-like (HR = 4.71, 95% CI = 2.24-9.93). Additional subtyping of HR+ patients by PAM50 provided future risk stratification where luminal B patients in this group had significant higher mortality than luminal A patients (HR = 3.93, 95% CI = 1.92-8.03). Similar results were also observed among 291 HR+/HER2- patients, but not among the HR- patients.
Our study suggests that for HR+ patients, especially HR+/HER2- patients, additional PAM50-based subtyping would provide better prognostic stratification and improve disease management.
我们在一项基于人群的乳腺癌研究中评估了免疫组织化学（IHC）与 PAM50 为基础的亚型对乳腺癌死亡率的预后能力。
我们共纳入了来自基于人群的长岛乳腺癌研究项目（LIBCSP）的 463 例乳腺癌病例。从病历中提取 IHC 标志物，而基于 PAM50 的内在亚型则使用 NanoString nCounter 分析系统从肿瘤组织中进行评估。Cox 比例风险模型用于估计与亚型相关的乳腺癌特异性死亡率的风险比（HRs）。
对于 IHC 为激素受体阳性（HR+）的肿瘤（n=361），68.7%通过 PAM50 分类为 luminal 亚型；对于 HR-肿瘤（n=102），95.1%被分类为非 luminal 亚型。与 HR+/HER2- 亚型相比，HR-患者的乳腺癌死亡率显著更高（HR-/HER2+：HR=2.84，95%CI=1.58-5.11；三阴性乳腺癌：HR=2.42，95%CI=1.44-4.06）。与 luminal A 相比，所有其他基于 PAM50 的亚型的死亡率均较高：luminal B（HR=4.03，95%CI=1.97-8.22）、HER2 富集型（HR=6.82，95%CI=3.29-14.14）和基底样（HR=4.71，95%CI=2.24-9.93）。通过 PAM50 对 HR+患者进行进一步亚组分析，可以提供未来的风险分层，其中该组中的 luminal B 患者的死亡率明显高于 luminal A 患者（HR=3.93，95%CI=1.92-8.03）。在 291 例 HR+/HER2- 患者中也观察到了类似的结果，但在 HR-患者中则没有。
我们的研究表明，对于 HR+患者，尤其是 HR+/HER2-患者，额外的 PAM50 为基础的亚型分类将提供更好的预后分层，并改善疾病管理。
