Background: In estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative breast cancers, the progesterone receptor (PR) is an independent prognostic marker. Little is known about the prognostic value of PR by tumor grade. We assessed this in two independent datasets.
Patients and methods: Women with primary operable, invasive ER+ HER-2 negative breast cancer diagnosed between 2000 and 2012, treated at University Hospitals Leuven, were included. We assessed the association of PR status and subtype (grade 1-2 vs. grade 3) with distant recurrence-free interval (DRFI) and breast cancer-specific survival. The interaction between PR status and subtype was investigated, and associations of PR status by subtype were calculated. The BIG 1-98 data set was used for validation.
Results: In total, 4,228 patients from Leuven and 5,419 from BIG 1-98 were analyzed. In the Leuven cohort, the adjusted hazard ratio (HR) of PR-positive versus PR-negative tumors for DRFI was 0.66 (95% confidence interval [CI], 0.50-0.89). For the interaction with subtype (p = .34), the HR of PR status was 0.79 (95% CI, 0.61-1.01) in luminal A-like and 0.59 (95% CI, 0.46-0.76) in luminal B-like tumors. In luminal A-like tumors, observed 5-year cumulative incidences of distant recurrence were 4.1% for PR-negative and 2.8% for PR-positive tumors, and in luminal B-like 18.7% and 9.2%, respectively. In the BIG 1-98 cohort, similar results were observed; for the interaction with subtype (p = .12), the adjusted HR of PR status for DRFI was 0.88 (95% CI, 0.57-1.35) in luminal A-like and 0.58 (95% CI, 0.43-0.77) in luminal B-like tumors. Observed 5-year cumulative incidences were similar.
Conclusion: PR positivity may be more protective against metastatic relapse in luminal B-like versus luminal A-like breast cancer, but no strong conclusions can be made. In absolute risk, results suggest an absent PR is clinically more important in high compared with low proliferative ER+ HER-2 negative tumors.
Implications for practice: An absent progesterone receptor (PR) predicts a worse outcome in women treated for an estrogen receptor-positive, human epidermal growth factor receptor 2 negative breast cancer. As low proliferative tumors lacking PR are now also classified high risk, the prognostic value of PR across risk groups was studied. Despite a negative test for interaction of the prognostic value of PR by tumor grade, the magnitude of an absent PR on breast cancer relapse is much larger in high than in low proliferative breast cancers.
摘要
背景。在雌激素受体阳性 (ER+)、人表皮生长因子受体 2 (HER‐2) 阴性乳腺癌中，孕激素受体 (PR) 是一种独立的预后指标。我们对于根据肿瘤级别估计的 PR 预后价值知之甚少。在 2 个独立的数据集中，我们对此进行了评估。
患者和方法。研究中包含在 2000 年至 2012 年期间被诊断出患有原发性可手术、浸润性 ER+ HER‐2 阴性乳腺癌并在鲁汶大学医院接受治疗的女性。利用无远端复发间期 (DRFI) 和乳腺癌相关生存率，我们评估了 PR 状态和亚型(1–2 级与 3 级)之间的关联。我们调查了 PR 状态和亚型之间的互相作用并推测出根据亚型估计的 PR 状态的关联。BIG 1‐98 数据集用于进行验证。
结果。我们一共分析了 4,228 名来自鲁汶的患者和 5,419 名来自 BIG 1‐98 的患者。在鲁汶队列中，针对 DRFI 的 PR 阳性肿瘤与 PR 阴性肿瘤的校正危害比 (HR) 为 0.66(95% 置信区间 [CI]，0.50–0.89)。就与亚型的相互作用而言 (p = .34)，在管腔 A 型肿瘤和管腔 B 型肿瘤中，PR 状态的 HR 为分别为 0.79(95% CI，0.61–1.01)和 0.59(95% CI，0.46–0.76)。在管腔 A 型肿瘤中，对于 PR 阴性肿瘤和 PR 阳性肿瘤，观察到的远端复发的 5 年累积发生率分别为 4.1% 和 2.8%，而在管腔 B 型肿瘤中，该发生率分别为 18.7% 和 9.2%。在 BIG 1‐98 队列中，我们观察到了相似的结果；就与亚型的相互作用而言 (p = .12)，在管腔 A 型肿瘤和管腔 B 型肿瘤中，针对 DRFI 的 PR 状态的校正 HR 分别为 0.88(95% CI，0.57–1.35)和 0.58(95% CI，0.43–0.77)。观察到的 5 年累积发生率相似。
结论。在管腔 B 型乳腺癌与管腔 A 型乳腺癌中，PR 阳性可能对转移性复发更具防护力，但是，我们未能得出有力的结论。在绝对风险方面，研究结果表明，与低增生性 ER+ HER‐2 阴性肿瘤相比，缺乏 PR 在高增生性 ER+ HER‐2 阴性肿瘤中具有更高的临床重要性。
对临床实践的提示:缺乏孕激素受体 (PR) 可以预测女性接受雌激素受体阳性、人表皮生长因子受体 2 阴性乳腺癌治疗的较差效果。由于缺乏 PR 的低增生性肿瘤现在也已被划分为高风险，所以，我们研究了各风险组之间的 PR 预后价值。尽管根据肿瘤等级对 PR 预后价值的相互作用进行了阴性检测，但是，就乳腺癌复发而言，在高增生性乳腺癌中 PR 的缺乏程度要远远高于低增生性乳腺癌。
Keywords: Age; Breast cancer; Luminal; Progesterone receptor; Prognostic value; Subtype.
© AlphaMed Press 2018.