Sihto Harri, Lundin Johan, Lehtimäki Tiina, Sarlomo-Rikala Maarit, Bützow Ralf, Holli Kaija, Sailas Liisa, Kataja Vesa, Lundin Mikael, Turpeenniemi-Hujanen Taina, Isola Jorma, Heikkilä Päivi, Joensuu Heikki
Laboratory of Molecular Oncology, Biomedicum, Helsinki University Central Hospital, Helsinki, Finland.
Clin Cancer Res. 2008 Jul 1;14(13):4103-10. doi: 10.1158/1078-0432.CCR-07-5003.
The frequency and significance of gene expression profile-derived molecular subtypes of breast cancers found in mammography screening are unknown.
We identified breast cancers diagnosed in women of any age living in defined geographic regions in Finland in 1991 to 1992 and collected clinical and pathologic data. Surrogates for the molecular subtypes were determined for 247 cancers found in organized mammography screening and 989 cancers detected outside of screening using immunohistochemistry or in situ hybridization. Molecular subtypes were defined as luminal A [estrogen receptor (ER) positive and/or progesterone receptor (PR) positive, HER2-], luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5+, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified. The median follow-up time was 9.4 years.
The luminal type A was common (73.7%) and the HER2+/ER- type is rare (5.7%) in screen-detected cancer, and only 16% were HER2 positive. Women with cancer diagnosed in screening at ages 50 to 69 years had similar molecular subtype distribution as women whose cancer was found outside of screening at age >69 years. In a multivariate model, cancer detection at screening independently predicted favorable distant disease-free survival when the molecular subtype was included as a covariate in addition to age, histologic grade, and cancer size. Women with small (pT(1)N(0)M(0)) HER2-positive cancer had similar outcome regardless of the method of detection.
Molecular subtype distribution of screen-detected breast cancer differs from that of cancers found outside of screening and accounts in part for the better outcome of screen-detected cancer.
在乳腺钼靶筛查中发现的乳腺癌基因表达谱衍生分子亚型的频率及意义尚不清楚。
我们确定了1991年至1992年在芬兰特定地理区域居住的任何年龄女性中诊断出的乳腺癌,并收集了临床和病理数据。使用免疫组织化学或原位杂交技术,对在有组织的乳腺钼靶筛查中发现的247例癌症以及在筛查外检测到的989例癌症确定分子亚型替代指标。分子亚型定义为腔面A型[雌激素受体(ER)阳性和/或孕激素受体(PR)阳性,HER2阴性]、腔面B型(ER阳性和/或PR阳性,HER2阳性)、基底样型(ER阴性、PR阴性、HER2阴性、细胞角蛋白5阳性和/或HER1阳性)、HER2阳性/ER阴性(ER阴性、PR阴性、HER2阳性)以及未分类型。中位随访时间为9.4年。
在筛查发现的癌症中,腔面A型常见(73.7%),HER2阳性/ER阴性型罕见(5.7%),且只有16%为HER2阳性。50至69岁筛查诊断为癌症的女性与69岁以上筛查外发现癌症的女性分子亚型分布相似。在多变量模型中,当分子亚型作为协变量与年龄、组织学分级和肿瘤大小一起纳入时,筛查时癌症检测独立预测远处无病生存良好。HER2阳性的小(pT(1)N(0)M(0))癌症女性无论检测方法如何,预后相似。
筛查发现的乳腺癌分子亚型分布与筛查外发现的癌症不同,部分解释了筛查发现癌症预后较好的原因。