新辅助化疗对浸润性乳腺癌分子标志物及分子分型的影响

目的研究乳腺癌新辅助化疗(NAC)(蒽环类联合紫衫类)过程中,雌激素受体(ER)、孕激素受体(PR)、HER2状态和Ki67值的变化,以及这些变化是否会对分子分型产生影响。方法回顾性分析从2011年11月到2015年6月期间在军事医学科学院附属医院行蒽环联合紫衫类NAC的137例浸润性乳腺癌患者。通过免疫组织化学方法测定NAC前后组织中ER、PR、HER2以及Ki67,并分为:Luminal A、Luminal B、三阴性和HER2阳性4种分子亚型。NAC前后分子标志物和分子分型的变化采用χ~2检验或用Fisher确切概率法检验,并用Kappa检验对新辅助化疗前后的分子标志物及分子分型进行一致性检验。结果 NAC前后ER、PR、HER2、Ki67的一致率分别为88.32%、83.21%、94.16%和75.91%。ER、PR、HER2在NAC前后变化差异均无统计学意义(P值均大于0.05)。在NAC后Ki67值平均数从35.75%降到了19.12%(P0.05)。除性激素受体(HR)阳性,HER2阴性型的肿瘤之外,其余病例的分子分型在NAC前后的结果一致(P=0.488)。NAC前后分子分型的一致率为57.66%,Kappa值=0.4020。结论 NAC会使浸润性乳腺癌Ki67的表达下降,并会影响HR阳性、HER2阴性型肿瘤的分子分型。     

乳腺浸润性导管癌分子亚型与临床病理特征及预后的关系

目的 检测乳腺浸润性导管癌的临床病理特征及特定蛋白的表达情况,对其进行分型,探讨各哑型与预后的关系.方法 采用免疫组织化学EnVision法检测128例浸润性导管癌ER、PR、HER2和CK5/6的表达,参考文献报道的免疫分型方法 对其分型,并对HER2过表达型9例进行FISH检测.结果 ER、PR、HER2和CKS/6在本组128例浸润性导管癌中的阳性表达率分别为67%(86/128)、45%(58/128)、27%(34/128)和27%(34/128),并将128例分为5种免疫哑型,管腔A型55%(70/128),管腔B型20%(25/128),HER2过表达型7%(9/128),基底细胞样型10%(13/128),无法分类型8%(11/128).FISH检测HER2过表达型9例均为HER2基因扩增.各分子亚型间预后差异具有统计学意义,管腔A型预后最好,基底细胞型预后较差.多因素分析,乳腺癌临床分期和免疫分型是独立的预后因素.月经状态在乳腺癌各免疫亚型中的分布差异有统计学意义.结论 通过检测ER、PR、HER2和CK5/6的表达可以将乳腺浸润性导管癌分成具有不同生物学行为的5个免疫亚型,对于评估预后,指导治疗具有一定的意义.     

乳腺浸润性导管癌分子亚型与临床病理特征及预后的关系

目的 检测乳腺浸润性导管癌的临床病理特征及特定蛋白的表达情况,对其进行分型,探讨各哑型与预后的关系.方法 采用免疫组织化学EnVision法检测128例浸润性导管癌ER、PR、HER2和CK5/6的表达,参考文献报道的免疫分型方法 对其分型,并对HER2过表达型9例进行FISH检测.结果 ER、PR、HER2和CKS/6在本组128例浸润性导管癌中的阳性表达率分别为67%(86/128)、45%(58/128)、27%(34/128)和27%(34/128),并将128例分为5种免疫哑型,管腔A型55%(70/128),管腔B型20%(25/128),HER2过表达型7%(9/128),基底细胞样型10%(13/128),无法分类型8%(11/128).FISH检测HER2过表达型9例均为HER2基因扩增.各分子亚型间预后差异具有统计学意义,管腔A型预后最好,基底细胞型预后较差.多因素分析,乳腺癌临床分期和免疫分型是独立的预后因素.月经状态在乳腺癌各免疫亚型中的分布差异有统计学意义.结论 通过检测ER、PR、HER2和CK5/6的表达可以将乳腺浸润性导管癌分成具有不同生物学行为的5个免疫亚型,对于评估预后,指导治疗具有一定的意义.     

乳腺浸润性导管癌分子亚型与临床病理特征及预后的关系

目的 检测乳腺浸润性导管癌的临床病理特征及特定蛋白的表达情况,对其进行分型,探讨各哑型与预后的关系.方法 采用免疫组织化学EnVision法检测128例浸润性导管癌ER、PR、HER2和CK5/6的表达,参考文献报道的免疫分型方法 对其分型,并对HER2过表达型9例进行FISH检测.结果 ER、PR、HER2和CKS/6在本组128例浸润性导管癌中的阳性表达率分别为67%(86/128)、45%(58/128)、27%(34/128)和27%(34/128),并将128例分为5种免疫哑型,管腔A型55%(70/128),管腔B型20%(25/128),HER2过表达型7%(9/128),基底细胞样型10%(13/128),无法分类型8%(11/128).FISH检测HER2过表达型9例均为HER2基因扩增.各分子亚型间预后差异具有统计学意义,管腔A型预后最好,基底细胞型预后较差.多因素分析,乳腺癌临床分期和免疫分型是独立的预后因素.月经状态在乳腺癌各免疫亚型中的分布差异有统计学意义.结论 通过检测ER、PR、HER2和CK5/6的表达可以将乳腺浸润性导管癌分成具有不同生物学行为的5个免疫亚型,对于评估预后,指导治疗具有一定的意义.     

乳腺导管内癌分子分型应用研究

目的 采用免疫组织化学检测方法 对乳腺导管内癌进行分子分型.方法 收集50例乳腺导管内癌存档蜡块,用单克隆抗体CK5/6、CK8、CK18、34βE12、p63、S-100、SMA、CD10、CD117、EGFR、ER、PR和HER2进行免疫组织化学EnVision法染色,按照免疫表型分为5种类型:腺腔A型(ER+/PR+/HER2-)、腺腔B型(ER+/PR+/HER2+)、正常乳腺样型(ER-/PR-/HER2-且不表达基底/肌上皮标记及EGFR)、HER2过表达型(ER-/PR-/HER2+)和基底细胞样型(ER-/PR-/HER2-,且至少表达一种基底型角蛋白和(或)肌上皮标记物或EGFR).结果 腺腔A型16例(32%),腺腔B型19例(38%),HER2过表达型13例(26%),基底细胞样型2例(4%),无正常乳腺型.2例基底细胞样型,均表达CK5/6、CD117,例1同时表达SMA,例2表达CK8、CK18、34βE12、S-100,均为高级别导管内癌.结论 乳腺导管内癌可按免疫表型进行分子分型,部分导管内癌具有与基底细胞样癌相同的免疫表型,可能是基底细胞样癌的前驱病变,其诊断依赖于免疫组化检测.     

基底细胞样型乳腺癌的临床病理观察

目的 观察基底细胞样型乳腺癌(BLBC)的临床病理特征.方法 采用ER、PR、HER2、Ki-67、CK5/6、CK14和表皮生长因子受体(EGFR)进行免疫组织化学EnVision法检测458例女性浸润性乳腺癌以筛选BLBC,比较BLBC与其他免疫表型乳腺癌的临床病理特征.对其中228例浸润性乳腺癌患者进行了随访.结果 458例浸润性乳腺癌中发现BLBC 46例(10.0%).癌灶直径平均3.3 cm.58.7%(27/46)出现推挤性生长方式,52.2%(24/46)出现地图状坏死,30.4%(14/46)癌灶中心出现无细胞纤维化区域以及63.0%(29/46)癌灶周边和间质内有不同程度淋巴细胞浸润.癌细胞异型性明显,核分裂象多见,主要排列成不规则、紧密实性结构.Ki-67高表达(>25%)在BLBC中占43.5%(20/46).CK5/6、CK14和EGFR阳性分别见于58.7%(27/46)、43.5%(20/46)和65.2%(30/46)的BLBC病例.BLBC的3年累积生存率为66.9%,低于管腔A型乳腺癌,与HER2高表达型乳腺癌差异无统计学意义.结论 BLBC在女性浸润性乳腺癌中所占比例为10%,其组织结构和细胞形态具有一定特征性,但诊断BLBC仍必需结合其免疫表型.BLBC是预后比较差的乳腺癌亚型之一.     

缺氧诱导因子-1α与非特殊型浸润性乳腺癌分子分型及血管生成的关系分析

目的:探讨缺氧诱导因子-1α(HIF-1α)在非特殊型浸润性乳腺癌(IBC-NST)中的表达及其与乳腺癌分子分型、血管生成等的关系。方法:收集IBC-NST组织150例,应用免疫组织化学法(IHC)检测乳腺癌组织中HIF-1α、人类表皮生长因子受体2(HER2)、雌激素受体(ER)、孕激素受体(PR)、细胞增殖相关核抗原Ki67、血管内皮细胞标记CD34的表达情况,并检测30例癌旁正常乳腺组织中HIF-1α、CD34的表达作为对照;另以荧光原位杂交法(FISH)进一步检测HER2 IHC 2+的乳腺癌组织中HER2基因扩增情况;分析HIF-1α与乳腺癌分子分型、CD34标记的微血管密度(MVD)、年龄、病理分级以及TNM分期等的关系。结果:在150例IBC-NST中HIF-1α表达阳性率为61. 3%,MVD为28. 37±7. 83,均高于正常对照组,差异均具有统计学意义(P0. 05); HER2过表达型或三阴性型乳腺癌HIF-1α阳性率均高于Luminal A型或B型,且Luminal B型高于Luminal A型,差异均具有统计学意义(P0. 05); HIF-1α阳性组乳腺癌ER、PR阳性率低于HIF-1α阴性组,而HIF-1α阳性组Ki67表达指数、MVD则高于HIF-1α阴性组,且Ⅲ～Ⅳ期乳腺癌HIF-1α阳性率高于Ⅰ～Ⅱ期,差异均具有统计学意义(P 0. 05); HIF-1α阳性与阴性乳腺癌组间HER2表达差异无统计学意义(P0. 05),不同年龄、病理分级乳腺癌组间HIF-1α表达差异无统计学意义(P0. 05)。结论:IBC-NST不同分子分型中HIF-1α差异表达,HER2过表达型和三阴性型中HIF-1α表达阳性率高,HIF-1α抑制乳腺癌ER、PR表达,提高Ki67增殖指数; HIF-1α对乳腺癌血管生成、肿瘤进展具有促进作用; HIF-1α有望成为乳腺癌(尤其三阴性型)治疗的有效靶点及乳腺癌的预后指标。     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.     

雄激素受体在乳腺癌中的表达及其与雌、孕激素受体和HER2的关系

目的 研究雄激素受体(AR)在乳腺浸润性导管癌中的表达及其与雌激素受体(ER)、孕激素受体(PR)和HER2状态的关系,探讨其作为乳腺癌治疗靶点的可行性.方法 采用免疫组织化学EnVision法检测AR、ER、PR、HER2在175例乳腺浸润性导管癌中的表达,依据结果分为腺腔A型、腺腔B型、HER2过表达型和三阴性型(ER-/PR-/HER2-)组.结果 175例中AR阳性88例(50.3%),AR表达与ER、PR、HER2均呈正相关(P＜0.01).腺腔A型53例(30.3%),腺腔B型33例(18.9%),HER2过表达型23例(13.1%),三阴性型66例(37.7%),AR阳性率分别为56.6%(30/53),75.8%(25/33)、47.8%(11/23)和33.3%(22/66),组间AR阳性率差异显著(x2=17.054,P=0.001).三阴性型组AR阳性者核分裂象较少(x2=5.140,P=0.023),腺腔A型组AR阳性者多为年轻患者(x2=4.567,P=0.033),差异有统计学意义.其他组内AR表达与否和临床病理学特征比较无统计学意义.结论 AR在乳腺癌中有较高的阳性率,可作为乳腺癌,特别是三阴性型乳腺癌的治疗靶点.     

免疫组织化学诊断标准对基底细胞样型乳腺癌预后分析的影响

目的 探讨不同的免疫组织化学(IHC)诊断标准对基底细胞样型乳腺癌(BLBC)预后分析的影响及意义.方法 收集1996-2002年并有5年以上随访资料的浸润性乳腺癌284例,IHC检测ER、PR、HER2、CK5/6、CK14、表皮生长因子受体(EGFR)的表达,按照Nielsen标准[ER-/HER2-,CK5/6+和(或)EGFR+]、Kim标准[ER-/PR-/HER2-,CK5/6+和(或)CK14+和(或)EGFR+]、基底样CK标准[CK5/6+和(或)CK14+]、三阴性标准[ER-/PR-/HER2-]标准分型并比较其5年生存率.结果 在4种标准下,284例浸润性乳腺癌中BLBC的发病率分别为15.5%(44例)、14.8%(42例)、43.3%(123例)、21.1%(60例);复发率分别为18.2%(8/44)、21.4%(9/42)、10.6%(13/123)、11.7%(7/60),均明显高于其他亚型,但仅在Nielsen和Kim标准中之BLBC型的复发率与其他型差异有统计学意义.Nielsen和三阴性标准中BLBC型之5年无病生存率(均P<0.01)和5年总生存率(P<0.05和0.01)显著低于腺腔A型;Kim标准中BLBC型5年无病生存率显著低于腺腔A型(P<0.01),但5年总生存率与其他分型差异无统计学意义;基底样CK标准的BLBC型与非BLBC型之5年生存率差异无统计学意义.结论 在不同的IHC诊断标准下BLBC均呈高复发和预后差的趋势,但不同的分型标准影响其预后分析结果 ,相对完善、统一的诊断标准是亟待解决的问题.     

718例浸润性乳腺癌分子分型中CK5/6和EGFR的表达及临床病理分析

目的 探讨CK5/6和EGFR在浸润性乳腺癌(invasive breast carcinoma,IBC)分子分型中的表达及相关性.方法 采用免疫组化法检测718例IBC中CK5/6、EGFR、ER、PR、HER-2及Ki-67蛋白的表达,分析CK5/6、EGFR与IBC组织学类型、分子分型及其他相关标志物之间的关系....     

Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same?

There are 4 major molecular classifications in the literature that divide breast carcinoma into basal and nonbasal subtypes, with basal subtypes associated with poor prognosis. Basal subtype is defined as positive for cytokeratin (CK) 5/6, CK14, and/or CK17 in CK classification; negative for ER, PR, and HER2 in triple negative (TN) classification; negative for ER and negative or positive for HER2 in ER/HER2 classification; and positive for CK5/6, CK14, CK17, and/or EGFR; and negative for ER, PR, and HER2 in CK/TN classification. These classifications use similar terminology but different definitions; it is critical to understand the precise relationship between them. We compared these 4 classifications in 195 breast carcinomas and found that (1) the rates of basal subtypes varied from 5% to 36% for ductal carcinoma in situ and 14% to 40% for invasive ductal carcinoma. (2) The rates of basal subtypes varied from 19% to 76% for HG carcinoma and 1% to 7% for NHG carcinoma. (3) The rates of basal subtypes were strongly associated with tumor grades (P < .001) in all classifications and associated with tumor types (in situ versus invasive ductal carcinomas) in TN (P < .001) and CK/TN classifications (P = .035). (4) These classifications were related but not interchangeable (kappa ranges from 0.140 to 0.658 for HG carcinoma and from 0.098 to 0.654 for NHG carcinoma). In conclusion, although these classifications all divide breast carcinoma into basal and nonbasal subtypes, they are not interchangeable. More studies are needed to evaluate to their values in predicting prognosis and guiding individualized therapy.     

Identification of different subtypes of breast cancer using tissue microarray

Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC) characteristics. The main aim of the present study was to classify breast cancer into molecular subtypes based on immunohistochemistry findings and correlate the subtypes with clinicopathological factors. Two hundred and seventeen primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, EGFR, CK8/18, p53 and Ki67 using tissue microarray technique. All subtypes were significantly associated with Malay ethnic background (p=0.035) compared to other racial origins. The most common subtypes of breast cancers were luminal A and was significantly associated with low histological grade (p<0.000) and p53 negativity (p=0.003) compared to HER2+/ER-, basal-like and normal-like subtypes with high histological grade (p<0.000) and p53 positivity (p=0.003). Luminal B subtype had the smallest mean tumor size (p=0.009) and also the highest mean number of lymph nodes positive (p=0.032) compared to other subtypes. All markers except EGFR and Ki67 were significantly associated with the subtypes. The most common histological type was infiltrating ductal carcinoma, NOS. Majority of basal-like subtype showed comedo-type necrosis (68.8%) and infiltrative margin (81.3%). Our studies suggest that IHC can be used to identify the different subtypes of breast cancer and all subtypes were significantly associated with race, mean tumor size, mean number of lymph node positive, histological grade and all immunohistochemical markers except EGFR and Ki67.     

Molecular classification predicts survival for breast cancer patients in Vietnam: a single institutional retrospective analysis

Background: The Bhagarva surrogate molecular subtype definitions classify invasive breast cancer into seven the different subgroups based on immunohistochemical (IHC) criteria according to expression levels of markers as ER, PR, HER2, EGFR and/or basal cytokeratin (CK5/6) which are different in prognosis and responsiveness to adjuvant therapy. Purpose: The present study aimed to classify primary breast cancers and directly compares the prognostic significance of the intrinsic subtypes. Methods: The current study was conducted on 522 breast cancer patients who had surgery, but had not received neoadjuvant chemotherapy, from 2011 to 2014. The clinicopathologic characteristics were recorded. IHC staining was performed for ER, PR, HER2, Ki67, CK5/6, EGFR and D2-40 markers. All breast cancer patients were stratified according to Bhagarva criteria. The followed-up patients’ survival was analyzed by using Kaplan-Meier and Log-Rank models. Results: The luminal A (LUMA) was observed at the highest rate (32.5%). Non-basal-like triple negative phenotype (TNB-) and Luminal A HER2-Hybrid (LAHH) were the least common (3.3% in both). LUMA and luminal B (LUMB) were significantly associated with better prognostic features compared to HER2, basal-like triple negative phenotype (TNB+) and TNB-. Statistically significant differences were demonstrated between overall survival (OS), disease-free survival (DFS) and molecular subtypes (P<0.05), of which LUMB and LUMA had the highest rate of OS and DFS being 97.2 and 93.7%; and 97.2 and 90.5%, respectively. Conversely, HER2 revealed the worst prognosis with the lowest prevalence of OS and DFS (72.5 and 69.9%, respectively). Conclusion: The molecular subtypes had a distinct OS and DFS. The intrinsic stratification displayed inversely to clinicopathological features in breast cancer.     

Metaplastic breast carcinomas are basal-like tumours

AIMS: Recently, an immunohistochemical panel comprising antibodies against HER2, oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6 was reported to identify basal-like breast carcinomas, as defined by cDNA microarrays. Our aim was to analyse a series of metaplastic breast carcinomas (MBCs) using this panel plus two other basal markers (CK14 and p63) and progesterone receptor (PR), to define how frequently MBCs show a basal-like immunophenotype. METHODS AND RESULTS: Sixty-five cases were retrieved from the pathology archives of the authors' institutions and reviewed by three of the authors. Immunohistochemistry with antibodies for HER2, ER, EGFR, CK5/6, CK14 and p63 was performed according to standard methods. All but six cases (91%) showed the typical immunoprofile of basal-like tumours (ER- and HER2-, EGFR+ and/or CK5/6+). When CK14 and p63 were added to the panel, two additional cases could be classified as basal-like. The majority of MBCs lacked PR, except 4/19 (21%) carcinomas with squamous metaplasia. CONCLUSIONS: Our results demonstrate that MBCs show a basal-like phenotype, regardless of the type of metaplastic elements. Moreover, as these neoplasms frequently overexpress EGFR (57%), patients with MBC may benefit from treatment with anti-EGFR drugs.     

A subset of breast cancer predisposes to brain metastasis

This study evaluated the expression of biological markers of breast cancers with brain metastases. Eighteen paired tumors were assessed, with 42 non-brain-metastasizing breast cancers that were stained with ER, PR, HER2, CK5/6, p63, and Ki67, and were also classified into intrinsic subtypes. The expression patterns between the breast tumors with brain metastases were compared to the brain metastases and the controls. Breast cancers with brain metastases were of higher grade and showed higher incidence of lymph node metastases at initial diagnosis and higher EGFR, p63, and Ki67 expression. In the group of breast cancers with brain metastases, the brain metastases showed higher HER2, CK5/6, and Ki67 expression compared to the breast primaries. There was also a higher incidence of basal subtype and a lower incidence of luminal subtype. When tumors metastasized, changes in hormonal receptor (22%) and HER2 (6%) status were observed. We concluded that breast cancers with higher grade, lymph node involvement at diagnosis, high EGFR, p63, and Ki67 expression, and of basal subtype were at higher risk for brain metastases, and that both hormonal receptors and HER2 status may change in brain metastases.     

P-cadherin and cytokeratin 5: useful adjunct markers to distinguish basal-like ductal carcinomas in situ

Gene expression profiles of invasive breast carcinomas have identified a subgroup of tumours with worse prognosis, which have been called "basal-like". These are characterized by a specific pattern of expression, being estrogen receptor (ER) and HER2 negative, and frequently expressing at least one basal marker such as basal cytokeratins or epidermal growth factor receptor (EGFR). Previously, our group characterized basal-like tumours in a series of invasive breast carcinomas using P-cadherin (P-CD), p63 and cytokeratin 5 (CK5). Based on that study, we hypothesized that those high-grade basal-like invasive carcinomas might have a pre-invasive counterpart, which could be identified using the same approach. A series of 79 ductal carcinomas in situ (DCIS) were classified into distinct subgroups according to their ER, HER2 and basal markers expression. Luminal DCIS expressed ER and constituted 64.6% of the series; the HER2 overexpressing tumours did not express ER and represented 25.3% of the cases, whereas 10.1% lack the expression of ER and HER2 and expressed at least one basal marker (P-CD, CK5, CK14, p63, vimentin and/or EGFR). These basal-like DCIS were mostly high-grade, with comedo-type necrosis, and consistently showed expression of P-CD and CK5. In conclusion, DCIS with a basal-like phenotype represent a small percentage in our series, being P-CD and CK5, the most useful adjunct markers to distinguish this subset of carcinomas in situ of the breast.     

Identification of a basal-like subtype of breast ductal carcinoma in situ

Microarray profiling of invasive breast carcinomas has identified subtypes including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor-prognosis, basal-like tumors have been immunohistochemically characterized as estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study was to determine the prevalence of basal-like ductal carcinoma in situ in a population-based series of cases using immunohistochemical surrogates. A total of 245 pure ductal carcinoma in situ cases from a population-based, case-control study were evaluated for histologic characteristics and immunostained for ER, HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as: luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were unclassified (negative for all 4 defining markers). The basal-like subtype was associated with unfavorable prognostic variables including high-grade nuclei (P < .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001). These studies demonstrate the presence of a basal-like in situ carcinoma, a potential precursor lesion to invasive basal-like carcinoma.