浸润性乳腺癌是妇女最常见的恶性肿瘤,具有很高的异质性。大量研究表明，乳腺癌的异质性与其分子遗传学和基因表达模式的差异相关。Perou等(2000年)首先提出乳腺癌的分子分类的概念，并经后来诸多学者的研究逐步完善，基本确定为以下5个类型。该分类强调癌组织表达雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2,即C-erbB-2)的状态及其与治疗和预后的关系。
为低级别浸润性癌，ER+和(或)PR+，HER2-，是乳腺癌最常见的类型，亦高表达CK8、CK18。
也是低级别浸润性癌，但分化差些，ER+和(或)PR+，HER2+，笔者以为可称之为三阳型。导管Ａ型和Ｂ型均起源于导管上皮，共同特点是ER、PR表达阳性，肿瘤分化较好，区别在于HER2的表达不同。病理形态上均可见有腺样结构形成，间质浸润，有时可见少量导管原位癌结构。管腔A型内分泌治疗可有良好反应，管腔B型因HER2阳性，内分泌治疗加上曲妥珠单抗(赫赛汀，Herceptin)靶向治疗，可克服内分泌治疗的耐药性，延缓肿瘤的治疗时间，提高疗效。
为高级别浸润性癌，ER和PR阴性。HER2阳性者年龄较轻，病情进展较快，肿瘤体积较大，组织学分级较高，淋巴结转移较多，化疗缓解期短，对他莫替芬(TAM)产生耐药，无病生存(DFS)率和总生存(OS)率低，预后较差。自从1998年抗HER2单克隆抗体曲妥珠单抗用于临床以来，HER2阳性晚期乳腺癌的疗效显著提高。目前对于HER2的检测国内外已有规范的检测指南，规定一般先用IHC检测,HER2蛋白阳性(3+)者可作为建议患者接受曲妥珠单抗治疗的依据，不确定(2+)者需进一步应用FISH或CISH等方法进行HER2基因扩增状态的检测，或重复IHC做进一步检测。在病理形态上本型主要为浸润性导管癌，也可见少数浸润性小叶癌、微乳头状癌和黏液癌。
为高级别浸润性癌，ER-和(或)PR-，HER2-，又称三阴性乳腺癌(TNBC)。该型起源于导管基底层细胞（肌上皮细胞），高表达基底上皮细胞分子标志物（CK5/6,17）。绝大多数三阴性乳腺癌的基因表达特征与基底细胞样形乳腺癌相同。三阴性乳腺癌具有很高的侵袭性，预后很差。
免疫表型类似正常乳腺。国内一篇大宗(745例)乳腺癌分子分类研究显示，管腔A型占31.5%,管腔B型占12.8%,HER2过表达型占18.9%，基底细胞样型占19.1%，并证实分子分型与WHO组织学分型有一定相关性，但并非绝对对应。由于浸润性导管癌占绝大多数，所以在各个分子亚型中亦占绝对优势。特殊类型中，小管癌、经典小叶癌、浸润性筛状癌、神经内分泌癌和黏液癌多归类于管腔型；大汗腺癌和多形性小叶癌多归于HER2过度表达型；而髓样癌、化生性癌和腺样囊腺癌等归于基底细胞样型。
Immunohistochemical Identification of Breast Tumor Intrinsic Subtypes. 来自于2006年的文章 Race, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study
Subtype definitions were as follows:
luminal A (ER+ and/or progesterone receptor positive [PR+], HER2−)
luminal B (ER+ and/or PR+, HER2+)
basal-like (ER−, PR−, HER2−, cytokeratin 5/6 positive, and/or HER1+)
HER2+/ER− (ER−, PR−, and HER2+)
unclassified (negative for all 5 markers).
来自文章：2015-4-IHC classification of breast cancer subtypes in a large cohort of a clinical cancer registry: use in clinical routine for therapeutic decisions and its effect on survival
Immuno-histochemical analyses, i.e., estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 (4-IHC), defined the tumor biological subtypes Luminal A, Luminal B, HER2-like, and Basal-like.
Subtype-related differences in therapies and overall survival (OS) were analyzed using multivariable statistical methods.
4344 patients (97.0 %) could be classified into the four common tumor biological subtypes.
The two most frequent entities were Luminal A (48.4 %), Luminal B (24.8 %), HER2-like (17.8 %), and Basal-like subtype (9.0 %).
In the current study data from the Tumor Centre Regensburg (Bavaria, Germany) were analyzed. This high-quality population-based regional cancer registry was founded in 1991 and covers a population of more than 2.2 million people of Upper Palatinate and Lower Bavaria. Currently, the follow-up data of 241,250 patients are available.
本次统计分析只挑选那些在2000~2012这13年间患有原位乳腺癌，没有复发转移的患者，共计4480个女性患者。
结论：
In conclusion, the classification of tumor biological subtypes by the ER, PR, HER2, and Ki-67 biomarkers (4-IHC) is practical, simple, quite discriminative, informative, and—most importantly—clinically useful.
Montreal cohort of 87 patients hierarchically clustered across 30 genes predicative of immunohistochemical (IHC) breast cancer subtype. Prediction analysis of microarrays (PAM)-determined expression from 30 genes were indicative of IHC breast cancer subtype. Hierarchical clustering of patients (columns) and genes (rows) tends to segregate triple-negative (TN; indicated in black), HER2+ (indicated in yellow) and HR+ (indicated in blue) tumours. Red indicates upregulation and green downregulation of transcripts for genes labelled on the right. Gene transcript expression levels are Z-score normalised with a colour key indicated in the top left corner.
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