Breast Oncology Program, Dana-Farber Cancer Institute, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
JAMA Oncol. 2022 Aug 1;8(8):1177-1183. doi: 10.1001/jamaoncol.2022.2286.
It is unclear whether ERBB2-low breast cancer should be considered an individual biologic subtype distinct from ERBB2-0 breast cancer.
To investigate whether low ERBB2 expression is associated with distinct clinicopathologic characteristics and prognosis among patients with hormone receptor (HR)-positive and triple-negative breast cancer (TNBC).
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted using data from a prospectively maintained institutional database on all consecutive patients with breast cancer undergoing surgery between January 2016 and March 2021 at Dana-Farber Brigham Cancer Center. The study included 5235 patients with stage I through III, ERBB2-negative invasive breast cancer. Tumors were classified as ERBB2-low if they had an ERBB2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and ERBB2-0 if they had an ERBB2 IHC score of 0. Data were analyzed from September 2021 through January 2022.
Standard treatment according to institutional guidelines.
Comparison of clinicopathologic characteristics and disease outcomes (pathologic complete response rate [pCR], disease-free survival, distant disease-free survival, and overall survival) between patients with ERBB2-low and ERBB2-0 breast cancer.
Among 5235 patients with ERBB2-negative invasive breast cancer (5191 [99.2%] women; median [range] age at primary surgery, 59.0 [21.0-95.0] years), 2917 patients (55.7%) and 2318 patients (44.3%) had ERBB2-low and ERBB2-0 tumors, respectively. Expression of HR was significantly more common among ERBB2-low compared with ERBB2-0 tumors (2643 patients [90.6%] vs 1895 patients [81.8%]; P < .001). The rate of ERBB2-low tumors increased progressively, from 296 of 739 estrogen receptor (ER)-negative tumors (40.1%) to 31 of 67 ER-low (ie, ER 1%-9%) tumors (46.3%), 37 of 67 ER-moderate (ie, ER, 10%-49%) tumors (55.2%), 2047 of 3542 ER-high (ie, ER, 50%-95%) tumors (57.8%), and 499 of 803 ER-very high (ie, ER > 95%) tumors (62.1%) (P < .001). Among 675 patients receiving neoadjuvant chemotherapy, those with ERBB2-0 tumors experienced higher pCR rates (95 patients [26.8%] vs 53 patients [16.6%]; P = .002). However, there were no statistically significant differences in pCR rate between ERBB2-low and ERBB2-0 tumors when separately analyzing HR-positive, ER-low, HR-positive without ER-low, or TNBC tumors. In exploratory survival analysis, no differences by ERBB2-low expression in disease-free survival, distant disease-free survival, or overall survival were observed among patients with HR-positive tumors or TNBC.
The results of this cohort study did not support the interpretation of ERBB2-low breast cancer as a distinct biologic subtype. ERBB2-low expression was positively associated with level of ER expression, and ER-low tumors were enriched among ERBB2-0 tumors, suggesting that, given the worse prognosis of ER-low tumors, they may be associated with confounding of prognostic analyses of ERBB2-low expression.
尚不清楚 ERBB2-低水平乳腺癌是否应被视为与 ERBB2-0 乳腺癌不同的独立生物学亚型。
探究低水平 ERBB2 表达是否与激素受体（HR）阳性和三阴性乳腺癌（TNBC）患者的临床病理特征和预后相关。
设计、地点和参与者：这是一项使用前瞻性维护的机构数据库中数据进行的队列研究，纳入了 2016 年 1 月至 2021 年 3 月期间在达纳-法伯布列根癌症中心接受手术的所有 I 期至 III 期、ERBB2 阴性浸润性乳腺癌连续患者。肿瘤被分类为 ERBB2-低水平，如果它们的 ERBB2 免疫组化（IHC）评分为 1+或 2+，且原位杂交检测为阴性；如果它们的 ERBB2 IHC 评分为 0，则被分类为 ERBB2-0。数据于 2021 年 9 月至 2022 年 1 月进行分析。
根据机构指南进行标准治疗。
比较 ERBB2-低水平和 ERBB2-0 乳腺癌患者的临床病理特征和疾病结局（病理完全缓解率 [pCR]、无病生存、远处无病生存和总生存）。
在 5235 例 ERBB2 阴性浸润性乳腺癌患者（5191 例 [99.2%] 女性；原发性手术时的中位[范围]年龄，59.0[21.0-95.0]岁）中，2917 例（55.7%）和 2318 例（44.3%）患者的肿瘤分别为 ERBB2-低水平和 ERBB2-0 水平。与 ERBB2-0 肿瘤相比，ERBB2-低水平肿瘤中 HR 的表达明显更常见（2643 例 [90.6%] 比 1895 例 [81.8%]；P<0.001）。ERBB2-低水平肿瘤的比例逐渐增加，从 739 例雌激素受体（ER）阴性肿瘤中的 296 例（40.1%）到 67 例 ER 低水平（即 ER 1%-9%）肿瘤中的 31 例（46.3%），67 例 ER 中等水平（即 ER 10%-49%）肿瘤中的 37 例（55.2%），3542 例 ER 高水平（即 ER 50%-95%）肿瘤中的 2047 例（57.8%）和 803 例 ER 非常高水平（即 ER>95%）肿瘤中的 499 例（62.1%）（P<0.001）。在 675 例接受新辅助化疗的患者中，ERBB2-0 肿瘤患者的 pCR 率更高（95 例 [26.8%] 比 53 例 [16.6%]；P=0.002）。然而，当分别分析 HR 阳性、ER 低水平、HR 阳性无 ER 低水平或 TNBC 肿瘤时，ERBB2-低水平和 ERBB2-0 肿瘤的 pCR 率之间没有统计学上的显著差异。在探索性生存分析中，在 HR 阳性肿瘤或 TNBC 患者中，未观察到 ERBB2-低水平表达在无病生存、远处无病生存或总生存方面的差异。
这项队列研究的结果不支持将 ERBB2-低水平乳腺癌视为一种独特的生物学亚型的解释。ERBB2-低水平表达与 ER 表达水平呈正相关，并且 ER 低水平肿瘤在 ERBB2-0 肿瘤中更为丰富，这表明鉴于 ER 低水平肿瘤的预后较差，它们可能与 ERBB2-低水平表达的预后分析混淆有关。
