Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy; Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Institut Jules Bordet, Academic Trials Promoting Team, Bruxelles, Belgium. Electronic address: https://twitter.com/Lucarecco.
U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Ann Oncol. 2024 Sep;35(9):792-804. doi: 10.1016/j.annonc.2024.06.009. Epub 2024 Jun 20.
Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes.
This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer].
From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype).
In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.
激素受体表达是乳腺癌的一个已知的阳性预后和预测因素；然而，关于其对携带 BRCA1 和/或 BRCA2 基因突变的年轻患者预后的预后影响的证据有限。
本国际多中心回顾性队列研究纳入了年轻（≤40 岁）诊断为浸润性乳腺癌且携带 BRCA 基因种系突变（PV）的患者。我们研究了激素受体状态对乳腺癌临床行为和结局的影响。根据激素受体表达（阳性与阴性）首先调查了无病生存期（DFS）、乳腺癌特异性生存期（BCSS）和总生存期（OS）等感兴趣的结局，然后根据乳腺癌亚型[管腔 A 样、管腔 B 样、三阴性和人表皮生长因子受体 2（HER2）阳性乳腺癌]进行了调查。
来自全球 78 个中心的 4709 名 BRCA 携带者被纳入研究，其中 2143 名（45.5%）患有激素受体阳性乳腺癌，2566 名（54.5%）患有激素受体阴性乳腺癌。中位随访时间为 7.9 年。激素受体阳性疾病患者远处复发率较高（13.1%比 9.6%，P<0.001），而激素受体阴性疾病患者第二原发乳腺癌发生率较低（9.1%比 14.7%，P<0.001）。激素受体阳性和阴性疾病患者的 8 年 DFS 分别为 65.8%和 63.4%。激素受体阳性与阴性疾病的 DFS、BCSS 和 OS 的风险比随时间变化（激素受体状态与生存时间的交互作用 P<0.05）。在 DFS 方面，管腔 A 样乳腺癌患者的长期预后最差，与所有其他亚组相比（8 年 DFS：管腔 A 样 60.8%，三阴性 63.5%，HER2 阳性 65.5%，管腔 B 样 69.7%）。
在年轻的 BRCA 携带者中，激素受体阳性与阴性疾病之间复发模式和第二原发乳腺癌的差异需要在治疗、随访和降低风险手术方面为患者提供咨询时考虑。
