Patel Jaymin M, Goss Andrew, Garber Judy E, Torous Vanda, Richardson Edward T, Haviland Miriam J, Hacker Michele R, Freeman Gordon J, Nalven Tessa, Alexander Brian, Lee Larissa, Collins Laura C, Schnitt Stuart J, Tung Nadine
Division of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA USA.
Harvard Medical School, Boston, MA USA.
NPJ Breast Cancer. 2020 Jun 5;6:19. doi: 10.1038/s41523-020-0160-4. eCollection 2020.
Retinoblastoma protein (Rb) is a product of the tumor suppressor gene. Its expression is highly prevalent in luminal breast cancers and is critical to the success of cyclin-dependent kinase (CDK) 4/6 inhibitor therapy. Expression of Rb in triple-negative breast cancer (TNBC), tumors generally associated with basal biology, is not well known. However, heterogeneity among TNBC and presence of subtypes with luminal features are well described. The purpose of this study was to determine prevalence and predictors of Rb protein expression in 1-associated and sporadic TNBCs. We studied 180 TNBC patients (70 1-associated and 110 sporadic). The clinical and pathologic features of these cases were previously assessed and reported. For this study, immunohistochemical stains for Rb were performed on tissue microarray sections. Details of treatment and outcome were abstracted from medical records. Fifty-one percent of TNBC were Rb positive (≥10% nuclei staining), and 85% of these cases had ≥50% nuclei staining. Rb expression was significantly associated with sporadic TNBC (71.4% vs 49.4%; < 0.001), androgen receptor (AR) expression (16.5% vs 3.4%; = 0.007), histologic grade 1 or 2 (9.9% vs 2.2%; = 0.04), and first recurrence in bone (8.8% vs 1.1%; = 0.03). Expression of p53 was not associated with Rb expression. Expression of Rb in TNBC was significantly associated with sporadic TNBC, AR expression, lower histologic grade, and metastasis to bone. These observations characterize a TNBC subtype with features suggestive of luminal-like biology and the potential to benefit from CDK 4/6 inhibition.
视网膜母细胞瘤蛋白(Rb)是肿瘤抑制基因的产物。其表达在管腔型乳腺癌中高度普遍,并且对于细胞周期蛋白依赖性激酶(CDK)4/6抑制剂治疗的成功至关重要。Rb在三阴性乳腺癌(TNBC)中的表达情况尚不明确,TNBC通常与基底生物学特征相关。然而,TNBC之间的异质性以及具有管腔特征的亚型的存在已得到充分描述。本研究的目的是确定1型相关和散发性TNBC中Rb蛋白表达的普遍性及预测因素。我们研究了180例TNBC患者(70例1型相关和110例散发性)。这些病例的临床和病理特征先前已进行评估并报告。在本研究中,对组织微阵列切片进行了Rb的免疫组织化学染色。治疗和结局的详细信息从病历中提取。51%的TNBC为Rb阳性(≥10%细胞核染色),其中85%的病例细胞核染色≥50%。Rb表达与散发性TNBC显著相关(71.4%对49.4%;P<0.001)、雄激素受体(AR)表达(16.5%对3.4%;P = 0.007)、组织学1级或2级(9.9%对2.2%;P = 0.04)以及首次骨转移(8.8%对1.1%;P = 0.03)。p53的表达与Rb表达无关。TNBC中Rb的表达与散发性TNBC、AR表达、较低的组织学分级以及骨转移显著相关。这些观察结果确定了一种TNBC亚型,其特征提示类似管腔样生物学特性,并且有可能从CDK 4/6抑制中获益。