Department of Medical Oncology, University Hospital, Besançon, France.
Oncologist. 2013 Jun;18(6):667-74. doi: 10.1634/theoncologist.2012-0350. Epub 2013 May 30.
The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance.
Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization.
From a cohort of 489 patients with mBC, 269 patients had histopathological samples of metastatic relapse. Histopathological analysis of the specimen confirmed the diagnosis of mBC in 235 patients. Discordance in one or more receptors between primary breast cancer and mBC was found in 99 patients (42%). A switch in receptor status was identified for ER in 17% of tumors (p = 4 × 10(-3)), PR in 29% of cancers (p < 4 × 10(-4)), and HER2 in 4% of lesions (p = .16). Exposure to chemotherapy and to anthracycline-based chemotherapy was statistically associated with switches in ER status. Seven (2%) second malignancies and three benign diseases (1%) were diagnosed.
This study confirms that discordance in ER and PR receptor expression between the primary breast tumor and the corresponding metastatic lesions is high, whereas HER2 status remains relatively constant. Chemotherapy, and specifically anthracycline-based chemotherapy, was associated with switch in ER status. These results were obtained in a selected population of patients; further studies are warranted to confirm these data and to determine the interest of systematic rebiopsy in the metastatic setting.
本回顾性研究的主要目的是探究原发性乳腺癌和转移性乳腺癌（MBC）之间雌激素受体（ER）状态、孕激素受体（PR）状态和 HER2 状态的个体内相关性。次要目的包括患者特征、总生存期、转移性疾病中组织病理学评估的可行性，以及与受体状态不一致相关的预测因素。
鉴定出接受转移性复发活检或转移手术的患者。从患者报告中回顾性获得人口统计学、肿瘤特征、治疗特征以及 ER、PR 和 HER2 状态。受体状态通过免疫组化评估，ER 和 PR 的阳性截断值为 10%以上。如果免疫组化中过表达评分达到 3+或荧光原位杂交中扩增率>2，则认为 HER2 为阳性。
在 489 例 MBC 患者中，269 例有 MBC 转移复发的组织病理学样本。对标本的组织病理学分析在 235 例患者中证实了 MBC 的诊断。在 99 例患者（42%）中发现原发性乳腺癌和 MBC 之间的一种或多种受体不一致。在 17%的肿瘤中（p=4×10（-3））、29%的癌症中（p<4×10（-4））和 4%的病变中（p=0.16）发现 ER 受体状态发生转换。接受化疗和蒽环类化疗与 ER 状态转换具有统计学相关性。诊断出 7 例（2%）第二恶性肿瘤和 3 例（1%）良性疾病。
本研究证实，原发性乳腺癌肿瘤和相应转移性病变之间 ER 和 PR 受体表达的不一致性很高，而 HER2 状态相对稳定。化疗，特别是蒽环类化疗，与 ER 状态转换相关。这些结果是在选定的患者人群中获得的；需要进一步研究来证实这些数据，并确定在转移性疾病中系统再活检的意义。
