Abstract：
BACKGROUND: 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.
METHODS: 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].
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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].
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：激素受体表达是乳腺癌中已知的阳性预后和预测因素；然而，关于其对携带BRCA致病变异体（PV）的年轻患者预后的影响的证据有限。
方法：这个国际，多中心，回顾性队列研究纳入了被诊断为浸润性乳腺癌并在BRCA基因中携带种系PV的年轻患者(≤40岁).我们研究了激素受体状态对乳腺癌临床行为和预后的影响。感兴趣的结果(无病生存[DFS]，首先根据激素受体表达（阳性与负)，然后根据乳腺癌亚型(腔A样与腔B样vs.三负vs.HER2阳性乳腺癌）。
结果：来自全球78个中心，包括4,709名BRCA运营商，其中2,143例(45.5%)患有激素受体阳性乳腺癌,2,566例(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的远处复发率较高（13.1%vs.9.6%,p<0.001)，而第二原发性乳腺癌的发病率较低(9.1%vs.14.7%,p<0.001）与激素受体阴性疾病的患者相比。激素受体阳性和阴性患者的8年DFS分别为65.8%和63.4%,分别。激素受体阳性与激素受体的危险比DFS的阴性疾病随时间变化，BCSS,和OS(对于激素受体状态和存活时间的相互作用,p<0.05)。与所有其他亚组相比，腔A样乳腺癌患者的DFS长期预后最差（8年DFS：腔A样乳腺癌60.8%三阴性与HER2阳性为65.5%，管腔B样亚型为69.7%）。
结论：在年轻的BRCA携带者中，激素受体阳性与第二原发性乳腺癌复发模式的差异阴性疾病值得在咨询患者治疗时考虑，后续行动,和降低风险的手术。
方法：这个国际，多中心，回顾性队列研究纳入了被诊断为浸润性乳腺癌并在BRCA基因中携带种系PV的年轻患者(≤40岁).我们研究了激素受体状态对乳腺癌临床行为和预后的影响。感兴趣的结果(无病生存[DFS]，首先根据激素受体表达（阳性与负)，然后根据乳腺癌亚型(腔A样与腔B样vs.三负vs.HER2阳性乳腺癌）。
结果：来自全球78个中心，包括4,709名BRCA运营商，其中2,143例(45.5%)患有激素受体阳性乳腺癌,2,566例(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的远处复发率较高（13.1%vs.9.6%,p<0.001)，而第二原发性乳腺癌的发病率较低(9.1%vs.14.7%,p<0.001）与激素受体阴性疾病的患者相比。激素受体阳性和阴性患者的8年DFS分别为65.8%和63.4%,分别。激素受体阳性与激素受体的危险比DFS的阴性疾病随时间变化，BCSS,和OS(对于激素受体状态和存活时间的相互作用,p<0.05)。与所有其他亚组相比，腔A样乳腺癌患者的DFS长期预后最差（8年DFS：腔A样乳腺癌60.8%三阴性与HER2阳性为65.5%，管腔B样亚型为69.7%）。
结论：在年轻的BRCA携带者中，激素受体阳性与第二原发性乳腺癌复发模式的差异阴性疾病值得在咨询患者治疗时考虑，后续行动,和降低风险的手术。
