Prasad Ramachandran, Boland Gary P, Cramer Angela, Anderson Elizabeth, Knox W Fiona, Bundred Nigel J
Department of Surgery, University Hospital of South Manchester, Manchester, United Kingdom.
Cancer. 2003 Dec 15;98(12):2539-46. doi: 10.1002/cncr.11836.
The biologic effect of continuing hormone replacement therapy (HRT) after a diagnosis of breast carcinoma is unclear. The goal of rhe current study was to determine the short-term effect of HRT withdrawal on invasive breast carcinoma using biologic surrogate markers of tumor response.
The study was performed between 1996 and 2000 and comprised 140 women who had been using HRT at the time of breast carcinoma diagnosis by core needle biopsy. The breast tumors were removed a median of 17 days later (range, 2-31 days). Of these women, 125 women stopped HRT at the time of core needle biopsy and 15 continued to receive HRT until surgery. In addition, 55 women with breast carcinoma from the same time period, who were not receiving HRT at diagnosis, were studied. Changes in expression of Ki-67 (a measure of epithelial cell proliferation), progesterone receptor (PR), p27KIP-1 (a cyclin-dependent kinase inhibitor), and cyclin D1 (a cell cycle-related protein) were determined by immunohistochemistry on paired sections of the core needle biopsy and surgical specimens from each patient.
In women who stopped HRT, a significant decrease in Ki-67 expression was observed between core needle biopsy and surgery in estrogen receptor (ER)-positive (n = 106; P < 0.001), but not in ER-negative tumors (n = 19; P = 0.58), with an associated reduction in PR (P < 0.001) and cyclin D1 expression (P < 0.001) and an increase in p27KIP-1 (P = 0.03). These changes in Ki-67 and PR expression occurred irrespective of c-erb-B2 status. No change was observed in any parameter in the other groups of patients.
ER-positive invasive breast carcinomas demonstrated a favorable biologic response to withdrawal of HRT. Therefore, HRT should be stopped at the time of diagnosis and was subsequently contraindicated.
乳腺癌确诊后继续进行激素替代疗法（HRT）的生物学效应尚不清楚。本研究的目的是使用肿瘤反应的生物学替代标志物来确定停用HRT对浸润性乳腺癌的短期影响。
该研究于1996年至2000年进行，纳入了140名在通过粗针活检诊断为乳腺癌时正在使用HRT的女性。乳腺肿瘤在中位时间17天后（范围为2 - 31天）切除。在这些女性中，125名女性在粗针活检时停用了HRT，15名继续接受HRT直至手术。此外，研究了同期55名诊断时未接受HRT的乳腺癌女性。通过免疫组织化学对每位患者粗针活检和手术标本的配对切片进行检测，确定Ki-67（上皮细胞增殖的指标）、孕激素受体（PR）、p27KIP-1（一种细胞周期蛋白依赖性激酶抑制剂）和细胞周期蛋白D1（一种细胞周期相关蛋白）表达的变化。
在停用HRT的女性中，雌激素受体（ER）阳性肿瘤（n = 106；P < 0.001）在粗针活检和手术之间观察到Ki-67表达显著降低，而ER阴性肿瘤（n = 19；P = 0.58）则未观察到，同时PR（P < 0.001）和细胞周期蛋白D1表达降低（P < 0.001），p27KIP-1增加（P = 0.03）。Ki-67和PR表达的这些变化与c-erb-B2状态无关。其他组患者的任何参数均未观察到变化。
ER阳性浸润性乳腺癌对停用HRT表现出良好的生物学反应。因此，HRT应在诊断时停用，随后禁用。
