Nishimukai Arisa, Yagi Tomoko, Yanai Ayako, Miyagawa Yoshimasa, Enomoto Yukie, Murase Keiko, Imamura Michiko, Takatsuka Yuichi, Sakita Isao, Hatada Takuya, Miyoshi Yasuo
Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Sakita Clinic, Nishinomiya, Hyogo, Japan.
Clin Breast Cancer. 2015 Jun;15(3):204-11. doi: 10.1016/j.clbc.2014.12.007. Epub 2014 Dec 24.
We examined the prognostic significance of progesterone receptor (PgR) expression in immunohistochemical-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration. The study included 327 surgically removed estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancers. High Ki-67 expression (> 15%) and low PgR expression (£ 20%) were significant independent factors resulting in worse distant relapse-free survival. This association was observed in postmenopausalwomen but not in premenopausal women.
Accurate classification of luminal A and luminal B characteristics of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is considered clinically important for determining effective adjuvant treatment. Although Ki-67 expression has been identified as an essential constituent for this classification, the role of progesterone receptor (PgR) expression has yet to be fully elucidated. Because PgR expression is influenced by the estrogen milieu, we examined the prognostic significance of PgR expression in immunohistochemical (IHC)-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration.
We examined 327 surgically removed ER(+) and HER2(-) breast cancer specimens. ER, PgR, and Ki67 expression was determined IHC for semiquantitative measurement. We used 1%, 20%, and 15% as the cutoff value for ER, PgR, and Ki-67, respectively.
Breast cancer with low PgR (≤ 20%) expression was significantly associated with postmenopausal status, a large tumor size, and low ER expression. The low PgR expression subset had significantly worse distant relapse-free survival (DRFS) than the high PgR expression subset (P = .0067). This association was observed consistently in postmenopausal women but not in the premenopausal women. Multivariate analysis demonstrated that high Ki-67 expression (hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.57-10.58; P = .003) and low PgR expression (HR, 2.54; 95% CI, 1.08-6.40; P = .038) were significant independent factors affecting DRFS.
Low PgR expression was independently associated with a poorer prognosis for ER(+) and HER2(-) breast cancer. Determination of PgR expression combined with that of Ki-67 could thus improve the accuracy of IHC-based classification of luminal A and luminal B breast cancer, especially for postmenopausal women.
我们在考虑绝经状态的情况下，研究了基于免疫组织化学的、由Ki-67表达定义的管腔亚型中孕激素受体（PgR）表达的预后意义。该研究纳入了327例手术切除的雌激素受体阳性且人表皮生长因子受体2阴性的乳腺癌。高Ki-67表达（>15%）和低PgR表达（≤20%）是导致远处无复发生存期较差的显著独立因素。这种关联在绝经后女性中观察到，但在绝经前女性中未观察到。
准确分类雌激素受体（ER）阳性且人表皮生长因子受体2（HER2）阴性乳腺癌的管腔A和管腔B特征被认为对于确定有效的辅助治疗在临床上很重要。尽管Ki-67表达已被确定为该分类的重要组成部分，但孕激素受体（PgR）表达的作用尚未完全阐明。由于PgR表达受雌激素环境影响，我们在考虑绝经状态的情况下，研究了基于免疫组织化学（IHC）的、由Ki-67表达定义的管腔亚型中PgR表达的预后意义。
我们检查了327例手术切除的ER(+)和HER2(-)乳腺癌标本。通过免疫组织化学（IHC）测定ER、PgR和Ki67表达以进行半定量测量。我们分别将1%、20%和15%用作ER、PgR和Ki-67的临界值。
低PgR（≤20%）表达的乳腺癌与绝经后状态、肿瘤大尺寸和低ER表达显著相关。低PgR表达亚组的远处无复发生存期（DRFS）明显比高PgR表达亚组差（P = 0.0067）。这种关联在绝经后女性中一致观察到，但在绝经前女性中未观察到。多因素分析表明高Ki-67表达（风险比[HR]，3.80；95%置信区间[CI]，1.57 - 10.58；P = 0.003）和低PgR表达（HR，2.54；95% CI，1.08 - 6.40；P = 0.038）是影响DRFS的显著独立因素。
低PgR表达与ER(+)和HER2(-)乳腺癌预后较差独立相关。因此，联合测定PgR表达和Ki-67表达可提高基于免疫组织化学对管腔A和管腔B乳腺癌分类的准确性，尤其是对于绝经后女性。
