雌激素受体、孕激素受体和HER2表达水平是乳腺癌全身治疗方法选择的依据，但是在疾病进程中可能发生变化，由阳转阴或由阴转阳（HER2还存在高、低、零表达互相转变）。各类指南均推荐对肿瘤转移灶进行再次活检，以重新评定受体状态和进行治疗决策。骨转移是最常见的乳腺癌转移部位之一，但是在技术上活检难度稍大，相关研究少，且受体状态变化对生存结局的真实影响极少谈及。 2022年11月21日，国际抗癌联盟《国际癌症杂志》在线发表复旦大学附属肿瘤医院林明曦、金奕滋、吕泓、胡夕春✉️、张剑✉️等学者的研究报告，首次探讨了乳腺癌原发灶与其骨转移灶受体表达水平的不一致率及其生存结局。 该单中心回顾研究对2011年1月～2020年12月复旦大学附属肿瘤医院经治的155例病理证实骨转移的乳腺癌患者进行回顾分析。- HER2由零转低：40.4%（17/42）此类患者适合接受新型抗体缀合药物治疗
根据多因素比例风险回归模型分析，受体变化的独立风险因素包括既往内分泌治疗和抗HER2治疗。 对于激素受体阳性HER2阴性乳腺癌，骨转移灶激素受体转阴与未转阴患者相比，一线治疗后：- 中位无进展生存：5.3比19.4个月（P=0.004）
- 中位总生存：32.1比67.8个月（P<0.001）
对转移部位数量进行校正后，骨转移灶激素受体转阴与未转阴患者相比，一线治疗后：- 进展或死亡风险高3.271倍（95%置信区间：1.06～10.09，P=0.039）
- 总死亡风险高6.09倍（95%置信区间：1.50～24.72，P=0.011）
HER2转阴对一线治疗后无进展生存和总生存影响不显著。 因此，该单中心回顾研究结果表明，乳腺癌骨转移后受体表达水平变化真实存在，并提供了各种变化率供业界参考；同时，这可能直接导致预后改变或导致后续治疗改变，最终显著影响生存结局。尤其值得注意的是，对肿瘤原发灶HER2零表达患者骨转移灶进行再次活检，有可能使患者获得新药（例如德曲妥珠单抗等新型抗体缀合药物）治疗机会，故有必要进一步开展多中心大样本前瞻研究进行验证。Int J Cancer. 2022 Nov 21. IF: 7.316Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases.Lin M, Jin Y, Lv H, Hu X, Zhang J.Fudan University Shanghai Cancer Center, China; Shanghai Medical College, Fudan University, Shanghai, China.ER, PgR, and HER-2 status are the cornerstones of choosing systemic therapy for breast cancer, but can change during the disease course. Guidelines recommended the biopsy of the metastatic tumor to reassess receptor status. Bone is the most frequent metastatic site of breast cancer but remained technically difficult to biopsy. Our study aimed to evaluate the incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. 155 breast cancer patients were diagnosed with pathology-confirmed bone metastasis at Fudan University Shanghai Cancer Center. 93 patients with receptor status available on both primary tumor and bone metastases were included in our study. ER, PgR, and HER-2 status converted from positive to negative in 10.8% (10/93), 28.0% (26/93), and 8.6% (8/93) of the patients, while ER, PgR, and HER-2 status converted from negative to positive in 3.2% (3/93), 4.3% (4/93), and 1.1% (1/93) of the patients, respectively. 40.4% (17/42) of the HER2-0 tumors converted to HER2-low, which enabled them to receive the treatment of new antibody-drug conjugates (ADCs). Prior endocrine and anti-HER2 therapy were the independent risk factors for receptor conversion. Loss of HR expression in bone metastases was significantly associated with worse first-line PFS (adjusted hazard ratio=3.271, P-value=0.039) and OS (adjusted hazard ratio=6.09, P-value=0.011). In conclusion, our study confirmed that patients may experience receptor conversion between primary breast cancer and bone metastases, possibly influenced by prior treatments, which significantly influenced prognosis. The re-biopsy of bone metastases in patients with primary HER2-0 tumors may benefit from the new ADC drugs.
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