Shanthala S, Amirtham Usha, Gopal Champaka, N Suma M, Jacob Linu, Babu Govinda
Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India.
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India.
South Asian J Cancer. 2023 Dec 8;13(2):90-98. doi: 10.1055/s-0043-1775807. eCollection 2024 Apr.
S. Shanthala Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines recommend rebiopsy of accessible metastatic lesions to reassess tissue biomarkers. While existing literature on biomarker changes is conflicting and heterogeneous, similar studies on the Indian cohort of breast cancer patients are lacking. In this context, we aimed to evaluate the frequencies of biomarker changes between biopsies from primary and recurrent sites, and their association with various clinicopathological characteristics, including the type of metastasis and treatment in metastatic breast cancer (MBC) patients. This is an ambispective study performed at a single center. Immunohistochemical (IHC) expression of paired primary and recurrence samples of MBC patients was reviewed for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67. Concordance, loss, and gain of receptors were assessed based on the Allred scores for ER, PR, and HER2. Ki-67 was assessed based on a 14% cutoff. Further, receptor changes were studied in relation to age, menopausal status, morphology, grade, stage, metastatic sites, interval between biopsies, and treatment. At progression, biopsies were obtained from 41.18% of locoregional recurrence and 58.82% of metastatic sites. Despite high discordance of 47% for ER and 68.6% for PR, true receptor conversion was observed in 9.8%, 21.56%, and 5.88% for ER, PR, and HER2, respectively. There was a significant correlation between age and ER discordance ( = 0.029). Loss in PR significantly correlated with a gain in Ki-67. Of all the metastatic sites, the lung was significantly associated with PR and Ki-67 concordance ( = 0.008 and = 0.0425, respectively). Discordance of receptors was neither related to the sites of biopsy (local recurrence or metastatic site) nor to the time interval between biopsies, prior chemotherapy, or hormone therapy. In conclusion, metastatic progression of the disease is accompanied by age-dependent discordance of ER. Unparalleled changes in PR in relation to ER suggest that ER-independent pathways may influence PR expression in MBC. Furthermore, the concurrence of PR loss with Ki-67 gain indicates an aggressive phenotype with disease progression. Hence, follow-up testing of samples for receptor expression is beneficial in determining prognosis and guiding therapeutic decisions.
S. 尚塔拉 原发性和转移部位之间受体的免疫表型不一致对治疗结果有显著影响。当前国际指南建议对可及的转移病灶进行再次活检，以重新评估组织生物标志物。虽然关于生物标志物变化的现有文献相互矛盾且参差不齐，但缺乏针对印度乳腺癌患者队列的类似研究。在此背景下，我们旨在评估原发性和复发部位活检之间生物标志物变化的频率，以及它们与各种临床病理特征的关联，包括转移类型和转移性乳腺癌（MBC）患者的治疗情况。这是一项在单一中心进行的前瞻性研究。回顾了MBC患者配对的原发性和复发样本的免疫组织化学（IHC）表达，以检测雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子2（HER2）和Ki-67的表达。根据ER、PR和HER2的阿尔雷德评分评估受体的一致性、缺失和增加情况。Ki-67根据14%的临界值进行评估。此外，还研究了受体变化与年龄、绝经状态、形态、分级、分期、转移部位、活检间隔时间以及治疗的关系。在疾病进展时，41.18%的局部区域复发和58.82%的转移部位进行了活检。尽管ER的不一致率高达47%，PR的不一致率高达68.6%，但ER、PR和HER2的真正受体转换率分别为9.8%、21.56%和5.88%。年龄与ER不一致之间存在显著相关性（P = 0.029）。PR的缺失与Ki-67的增加显著相关。在所有转移部位中，肺与PR和Ki-67的一致性显著相关（分别为P = 0.008和P = 0.0425）。受体的不一致既与活检部位（局部复发或转移部位）无关，也与活检间隔时间、先前的化疗或激素治疗无关。总之，疾病的转移进展伴随着与年龄相关的ER不一致。PR与ER的变化不一致表明，ER非依赖性途径可能影响MBC中PR的表达。此外，PR缺失与Ki-67增加同时出现表明疾病进展时具有侵袭性表型。因此，对样本进行受体表达的随访检测有助于确定预后并指导治疗决策。
