Prognostic and predictive value of cell cycle progression (CCP) score in ductal carcinoma in situ of the breast.,Modern Pathology

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Prognostic and predictive value of cell cycle progression (CCP) score in ductal carcinoma in situ of the breast.
Modern Pathology ( IF 7.1 ) Pub Date : 2020-01-10 , DOI: 10.1038/s41379-020-0452-0
Matteo Lazzeroni ₁ , Andrea DeCensi _{2,

3} , Aliana Guerrieri-Gonzaga ₁ , Eleonora Pagan ₄ , Vincenzo Bagnardi ₄ , Debora Macis ₁ , Davide Serrano ₁ , Andrea Vingiani ₅ , Giuseppina Bonizzi ₅ , Massimo Barberis ₅ , Giancarlo Pruneri _{6,

7} , Susanne Wagner ₈ , Sara Gandini ₉ , Giuseppe Viale _{5,

7} , Bernardo Bonanni ₁

Affiliation

The natural history of ductal carcinoma in situ (DCIS) is highly variable and difficult to predict. Biomarkers are needed to stratify patients with DCIS for adjuvant therapy. We investigated the prognostic and predictive relevance of cell cycle progression (CCP) score in women with DCIS. We measured the expression of 23 genes involved in CCP with quantitative RT-PCR on RNA extracted from formalin-fixed paraffin-embedded tumor samples, and assessed the correlation of a predefined score with histopathologic features and recurrence. The signature was analyzed in a cohort of 909 consecutive DCIS with full histopathological features treated in a single institution. The main outcome measure was ipsilateral breast event (IBE) as first event observed, be it in situ or invasive. Median follow-up time was 8.7 years (IQR 6.5-10.5 years). There were 150 ipsilateral IBEs, 84 (56%) of which were invasive. In the first 5 years of follow-up, the score provided statistically different findings (p = 0.009), with IBE rates of 14.7% (95% CI, 10.4-19.7) for the highest quartile of CCP score (Q4) and 8.7% (95% CI, 6.7-11.0) for the lowest quartiles (Q1-3). The prognostic value for IBEs approached significance also in women treated with mastectomy (adjusted hazard ratio [HR] Q4 vs. Q1-3 = 2.60; 95% CI: 0.96-7.08; P = 0.06). Radiotherapy provided a greater benefit in women with higher CCP score. In addition, Q4 predicted a different risk after tamoxifen depending on menopausal status, with a beneficial trend on IBEs in postmenopausal women (HR 0.30; 95% CI, 0.07-1.39), and an opposite trend in premenopausal women (HR 1.68; 95% CI, 0.38-7.44) (P-interaction = 0.03). The results of this study provide for the first time the evidence that CCP score is a prognostic marker, which, after additional validation, could have an important role in personalizing the management of DCIS.

中文翻译：

细胞周期进程 (CCP) 评分在乳腺导管原位癌中的预后和预测价值。

导管原位癌 (DCIS) 的自然病程变化很大且难以预测。需要生物标志物来对 DCIS 患者进行分层以进行辅助治疗。我们研究了 DCIS 女性细胞周期进展 (CCP) 评分的预后和预测相关性。我们对从福尔马林固定石蜡包埋的肿瘤样本中提取的 RNA 进行定量 RT-PCR 测量了 23 个参与 CCP 的基因的表达，并评估了预定义评分与组织病理学特征和复发的相关性。在同一机构治疗的具有完整组织病理学特征的 909 例连续 DCIS 队列中分析了特征。主要结果测量是同侧乳房事件 (IBE) 作为观察到的第一个事件，无论是原位还是侵入性。中位随访时间为 8.7 年（IQR 6.5-10.5 年）。有 150 例同侧 IBE，其中 84 例 (56%) 为侵入性。在前 5 年的随访中，分数提供了统计上不同的发现 (p = 0.009)，CCP 分数最高四分位数 (Q4) 的 IBE 率为 14.7%（95% CI，10.4-19.7）和 8.7% (95% CI, 6.7-11.0) 对于最低四分位数 (Q1-3)。IBE 的预后价值在接受乳房切除术治疗的女性中也接近显着（调整后的风险比 [HR] Q4 与 Q1-3 = 2.60；95% CI：0.96-7.08；P = 0.06）。放疗为 CCP 评分较高的女性提供了更大的益处。此外，根据绝经状态，Q4 预测了他莫昔芬后的不同风险，绝经后妇女的 IBE 呈有益趋势（HR 0.30；95% CI，0.07-1.39），绝经前妇女呈相反趋势（HR 1.68；95%） CI, 0.38-7.44) (P-相互作用 = 0.03)。

更新日期：2020-01-11

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