Background

CDK4/6 inhibitors have been used to treat hormone receptor-positive HER2-negative advanced breast cancer. Their benefit in HER2-positive breast cancer has not been determined yet. In this study, we investigated the effects of HER2 on CDK4/6 activity by assessing the level of downstream phosphorylated retinoblastoma protein (pRb) in HER2-positive breast cancer (HER2 positivity is defined by immunohistochemical study or FISH, regardless of ER status) to determine if these cases may be responsive to CDK4/6 inhibitors.

Materials and Methods

One hundred and thirty cases of breast biopsies with invasive carcinoma were collected, including 77 cases of HER2+ (39 cases of ER +PR±HER2+ and 38 cases of ER-PR-HER2+) and 53 cases of HER2- (ER-PR-HER2-) breast cancer. Immunohistochemical study of pRb was performed and the pRb level was assessed by H-score (intensity x percentage of positive cells).

Results

The pRb H-score ranges from 3 to 270. The average H-scores for the ER-PR-HER2+, ER+PR±HER2+ and ER-PR-HER2- groups are 115.8 ± 75.8, 93.1 ± 68.6 and 63.1 ± 65.6, respectively. By comparison, HER2+ cases have significantly higher pRb levels than HER2- cases (P = .001). Among HER2+ cases, there was a trend of positive correlation between the HER2 gene copy number, and the pRb level although not statistically significant (r = 0.192, 95% CI, [-0.033, 0.399], P = .09).

Conclusion

In breast cancer, HER2 positivity leads to significantly higher levels of CDK4/6 activity as reflexed by pRb. Breast cancer that is positive for HER2 may respond to CDK4/6 inhibitors and pRb may potentially be used as a biomarker to predict the responsiveness.

中文翻译：

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HER2对乳腺癌CDK4/6活性的影响

背景

CDK4/6 抑制剂已被用于治疗激素受体阳性 HER2 阴性晚期乳腺癌。它们在 HER2 阳性乳腺癌中的益处尚未确定。在这项研究中，我们通过评估 HER2 阳性乳腺癌中下游磷酸化视网膜母细胞瘤蛋白 (pRb) 的水平来研究 HER2 对 CDK4/6 活性的影响（HER2 阳性由免疫组织化学研究或 FISH 定义，无论 ER 状态如何）确定这些病例是否对 CDK4/6 抑制剂有反应。

材料和方法

收集130例浸润性癌乳腺活检，其中HER2+ 77例（ER+PR±HER2+ 39例，ER-PR-HER2+ 38例）和HER2-（ER-PR-HER2）53例-） 乳腺癌。对 pRb 进行免疫组织化学研究，并通过 H 评分（强度 x 阳性细胞百分比）评估 pRb 水平。

结果

pRb H 评分范围为 3 至 270。ER-PR-HER2+、ER+PR±HER2+ 和 ER-PR-HER2- 组的平均 H 评分为 115.8 ± 75.8、93.1 ± 68.6 和 63.1 ± 65.6，分别。相比之下，HER2+ 病例的 pRb 水平显着高于 HER2- 病例 ( P = . 001)。在HER2+病例中，HER2基因拷贝数与pRb水平呈正相关趋势，但无统计学意义（r  = 0.192, 95% CI, [-0.033, 0.399], P = . 09）。

结论

在乳腺癌中，HER2 阳性导致 CDK4/6 活性水平显着升高，这由 pRb 反映。HER2 阳性的乳腺癌可能对 CDK4/6 抑制剂有反应，而 pRb 可能被用作预测反应性的生物标志物。