目录
1. PHASE 1 STUDY OF REZATAPOPT, A P53 REACTIVATOR, IN TP53 Y220C–MUTATED TUMORS
首个P53激活剂REZATAPOPT在TP53 Y220C突变肿瘤的Ⅰ期研究
（NEJM，IF=176.08 ）
2. OVERALL SURVIVAL WITH FIRST-LINE VS SECOND-LINE CDK4/6 INHIBITOR USE IN ADVANCED BREAST CANCER A RANDOMIZED CLINICAL TRIAL
晚期乳腺癌一线与二线CDK4/6抑制剂治疗的总生存期：一项随机临床试验
（JAMA Oncology，IF=20.10 ）
3.REAL-WORLD USE AND SURVIVAL OUTCOMES OF SACITUZUMAB GOVITECAN IN METASTATIC TRIPLE-NEGATIVE BREAST CANCER AND HORMONE RECEPTOR-POSITIVE/HER2-NEGATIVE METASTATIC BREAST CANCER
真实世界中 SACITUZUMAB GOVITECAN 在转移性三阴性乳腺癌及 HR+/HER2- 转移性乳腺癌中的应用及生存结局
（British Journal of Cancer，IF=9.30 ）
4. PATHWAY ACTIVITY PROFILING CAN PREDICT NEOADJUVANT ENDOCRINE THERAPY RESPONSE IN HR+ HER2- POSTMENOPAUSAL EARLY STAGE BREAST CANCER
通路活性分析可预测 HR+ HER2- 绝经后早期乳腺癌患者的新辅助内分泌治疗反应
（Breast Cancer Research，IF=6.10 ）
5. BREAST CANCER STAGING FOR PATIENTS WITH “LOW‐RISK” DISEASE: ARE THEY ALL THE SAME？
低危乳腺癌患者的分期：他们是否都一样？
（Cancer，IF=5.10 ）
6. SURVIVAL OUTCOMES WITH OR WITHOUT RISK-REDUCING MASTECTOMY IN BRCA1 AND BRCA2 PATHOGENIC VARIANT CARRIERS
BRCA1和BRCA2致病性突变携带者接受或不接受降低风险乳房切除术的生存结局
（Breast Cancer，IF=2.90 ）
1. Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C–Mutated Tumors
首个P53激活剂Rezatapopt 在TP53 Y220C突变肿瘤的Ⅰ期研究
（NEJM，IF=176.08 ）
Abstract：
Background:
Rezatapopt is an investigational, first-in-class, oral, selective p53 reactivator that specifically binds to Y220C-mutated p53, which stabilizes p53 in its wild-type conformation and restores its functionality.
研究背景：
Rezatapopt 是一种在研的、首创的、口服、选择性 p53 再激活剂，其作用机制是特异性结合Y220C突变的p53，从而稳定 p53 的野生型构象并恢复其功能。
Methods:
In this phase 1, single-group, dose-escalation and dose-optimization study, we assigned heavily pretreated patients with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation to receive rezatapopt during continuous 21-day treatment cycles. The primary objectives were to determine the maximum tolerated dose and recommended phase 2 dose. Primary end points included dose-limiting toxic effects and adverse events. Secondary end points included preliminary efficacy and pharmacokinetic features.
研究方法：
这是一项 I 期、单组、剂量递增及剂量优化的研究，旨在评估 Rezatapopt 在携带 TP53 Y220C 突变的晚期实体瘤患者中的安全性、耐受性、药代动力学（PK）及初步疗效。患者接受 Rezatapopt 口服给药，起始剂量逐步递增，随后进行剂量优化，以确定推荐的 II 期剂量（RP2D）。主要终点包括 安全性和耐受性，次要终点包括药代动力学参数、客观缓解率（ORR）、疾病控制率（DCR）及缓解持续时间（DoR）。
Results:
A total of 77 patients received rezatapopt at one of eight escalating doses: 150 mg, 300 mg, 600 mg, 1150 mg, 1500 mg, 2000 mg, or 2500 mg once daily or 1500 mg twice daily. The maximum tolerated dose was 1500 mg twice daily. On the basis of safety, efficacy, and pharmacokinetic data, 2000 mg once daily with food was selected as the recommended phase 2 dose. During the treatment period, 76 patients (99%) had at least one adverse event and 29 (38%) had an adverse event of grade 1 or 2. The most common adverse events were nausea (in 58% of patients), vomiting (in 44%), an increased blood creatinine level (in 39%), fatigue (in 39%), and anemia (in 36%). Treatment-related adverse events occurred in 67 patients (87%) and those of grade 1 or 2 in 48 (62%); 2 patients (3%) discontinued rezatapopt because of a treatment-related adverse event. Most gastrointestinal adverse events resolved with the treatment of symptoms and were less frequent when rezatapopt was given with food. Anemia was the most common adverse event of grade 3 or higher during the treatment period, occurring in 16% of patients. The overall response (complete or partial response) was 20% among all patients and 30% among those who had a KRAS wild-type tumor and received a dose of at least 1150 mg once daily. Confirmed responses were seen across multiple tumor types, including ovarian and breast cancers. All patients with a response had a solid tumor that harbored TP53 Y220C and wild-type KRAS.
研究结果：
共 77 名患者接受了 Rezatapopt 治疗，剂量分为八个递增水平：150 mg、300 mg、600 mg、1150 mg、1500 mg、2000 mg、2500 mg 每日一次，或 1500 mg 每日两次。最大耐受剂量（MTD）为 1500 mg 每日两次。基于安全性、疗效及药代动力学数据，最终选择 2000 mg 每日一次，随餐服用作为 II 期推荐剂量（RP2D）。在治疗期间，76 名患者（99%）出现至少一种不良事件（AE），其中 29 名（38%）出现 1–2 级不良事件。最常见的不良事件包括：恶心（58%）、呕吐（44%）、血肌酐升高（39%）、疲劳（39%）及贫血（36%）。治疗相关不良事件发生于 67 名患者（87%），其中 48 名（62%）为 1–2 级；2 名患者（3%）因治疗相关不良事件停药。大多数胃肠道不良事件在对症处理后缓解，且随餐服用 Rezatapopt 时发生率更低。贫血是治疗期间最常见的 ≥3 级不良事件，发生率为 16%。总体缓解率（ORR，完全缓解或部分缓解）在所有患者中为 20%，在 KRAS 野生型肿瘤且每日剂量 ≥1150 mg 的患者中为 30%。确认的缓解病例分布于多种肿瘤类型，包括卵巢癌和乳腺癌。所有出现缓解的患者均为携带 TP53 Y220C 突变且 KRAS 野生型的实体瘤。
Conclusions:
In this phase 1 study involving heavily pretreated patients, the most common adverse events associated with rezatapopt were nausea and vomiting. Antitumor activity occurred across multiple tumor types, providing proof of concept for p53 reactivation. (Funded by PMV Pharmaceuticals; PYNNACLE ClinicalTrials.gov number, NCT04585750.)
研究结论：
在这项针对多线治疗后患者的 I 期研究中，Rezatapopt 最常见的不良事件为恶心和呕吐。 其在多种肿瘤类型中显示出抗肿瘤活性，验证了 p53 再激活的概念。（本研究由 PMV Pharmaceuticals 资助；临床试验注册号 NCT04585750，PYNNACLE 研究）。
2. Overall Survival With First-Line vs Second-Line CDK4/6 Inhibitor Use in Advanced Breast Cancer A Randomized Clinical Trial
晚期乳腺癌一线与二线CDK4/6抑制剂治疗的总生存期：一项随机临床试验
（JAMA Oncology ，IF=20.10 ）
Abstract：
Background:
Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (CDK4/6i) combined with endocrine therapy are widely used in hormone receptor (HR)–positive, ERBB2-negative advanced breast cancer (ABC). The SONIA trial evaluates the optimal timing of CDK4/6i administration, either in first-line or second-line setting. To determine whether first-line CDK4/6i use is superior to second-line use in terms of overall survival (OS) and to provide an updated analysis of the primary end point of progression-free survival (PFS) after 2 lines of therapy.
研究背景：
细胞周期蛋白依赖性激酶4和6抑制剂（CDK4/6i）联合内分泌治疗广泛用于激素受体（HR）阳性、ERBB2阴性晚期乳腺癌（ABC）。SONIA试验评估CDK4/6i给药的最佳时机，即一线或二线治疗。旨在确定一线CDK4/6i治疗在总生存期（OS）方面是否优于二线治疗，并在2线治疗后对无进展生存期（PFS）主要终点进行更新分析。
Methods:
The phase 3 SONIA randomized clinical trial is a multicenter trial in the Netherlands. Patients with HR-positive, ERBB2-negative ABC who did not receive prior treatment for ABC were randomized 1:1 to receive CDK4/6i added to first-line or second-line endocrine therapy. Patients were enrolled between November 23, 2017, and September 1, 2021. Data cutoff for this prespecified updated analysis was September 1, 2024. Data were analyzed from February to May 2025. Aromatase inhibitor plus CDK4/6i as first-line treatment followed by fulvestrant as second-line treatment (CDK4/6i first-line group) vs aromatase inhibitor as first-line treatment followed by fulvestrant plus CDK4/6i as second-line treatment (CDK4/6i second-line group). The primary end point was PFS after 2 lines of therapy. OS was a key secondary end point, with a prespecified analysis when all patients had 3 or more years of follow-up.
研究方法：
SONIA 3期随机临床试验是荷兰的一项多中心试验。将既往未接受过ABC治疗的HR阳性、ERBB2阴性ABC患者按1:1随机分配至CDK4/6i联合一线或二线内分泌治疗组。患者入组时间为2017年11月23日至2021年9月1日。本次预设更新分析的数据截止日期为2024年9月1日。数据分析时间为2025年2月至5月。芳香化酶抑制剂联合 CDK4/6i 作为一线治疗，随后氟维司群作为二线治疗（CDK4/6i一线组） vs 芳香化酶抑制剂作为一线治疗，随后氟维司群联合CDK4/6i作为二线治疗（CDK4/6i二线组）。主要终点为2线治疗后的PFS。OS为关键次要终点，预设分析要求所有患者随访≥3年。
Results:
Of 1050 enrolled patients, the median (IQR) age was 64 (16) years. A total of 524 were randomized to the CDK4/6i first-line group and 526 patients to the CDK4/6i second-line group. At a median follow-up of 58.5 months (95%CI, 57.0-60.9), 606 deaths (57.7%) had occurred. The median OS was 47.9 months (95%CI, 44.0-54.3) with first-line CDK4/6i and 48.1 months (95%CI, 44.7-52.0) with second-line CDK4/6i (hazard ratio [HR], 0.91; 95%CI, 0.77-1.07; P = .24). A post hoc subgroup analysis suggested an OS benefit with first-line use in premenopausal patients (HR, 0.53; 95%CI, 0.32-0.87) but not in postmenopausal patients (HR, 1.00; 95%CI, 0.84-1.19; P for interaction = .01). Among patients who discontinued second-line treatment, 257 of 303 in the first-line group (84.8%) and 303 of 360 in the second-line group (84.2%) received subsequent anticancer therapy, with similar treatment patterns. First-line CDK4/6i use was associated with more grade 3 or higher adverse events than second-line use (3400 vs 2242, respectively).
研究结果：
在入组的1050例患者中，中位（IQR）年龄为64（16）岁。524例随机分配至CDK4/6i一线组，526例分配至CDK4/6i二线组。中位随访58.5个月（95%CI，57.0-60.9）时，共发生606例死亡（57.7%）。一线CDK4/6i治疗的中位OS为47.9个月（95%CI， 44.0-54.3），二线CDK4/6i 治疗为48.1个月（95%CI，44.7-52.0）（风险比[HR]， 0.91；95%CI，0.77-1.07；P = .24）。事后亚组分析显示，绝经前患者一线使用有OS获益（HR，0.53；95%CI，0.32-0.87），但绝经后患者无获益（HR，1.00；95%CI，0.84-1.19；交互作用P = .01）。在停用二线治疗的患者中，一线组303例中的257例 （84.8%）和二线组360例中的303例（84.2%）接受了后续抗肿瘤治疗，治疗模式相似。一线CDK4/6i治疗与二线治疗相比，3级及以上不良事件更多（分别为3400例 vs 2242 例）。
Conclusions:
In this phase 3 randomized clinical trial, first-line CDK4/6i use did not improve OS compared with second-line use but did increase treatment-related toxic effects. Post hoc analysis suggests an OS benefit with first-line use in premenopausal patients.
研究结论：
在这项3期随机临床试验中，与二线使用相比，一线CDK4/6i治疗未能改善OS，但增加了治疗相关毒性。事后分析提示绝经前患者一线使用有OS获益。
3. Real-world use and survival outcomes of Sacituzumab govitecan in metastatic triple-negative breast cancer and hormone receptor-positive/HER2-negative metastatic breast cancer
真实世界中 Sacituzumab govitecan 在转移性三阴性乳腺癌及 HR+/HER2- 转移性乳腺 癌中的应用及生存结局
（British Journal of Cancer，IF=9.30 ）
Abstract：
Background:
Sacituzumab govitecan (SG) was granted early access in France as third-line therapy for metastatic triple-negative breast cancer (mTNBC) and hormone receptor-positive/HER2-negative (HR+/HER2–mBC) metastatic breast cancer. This nationwide cohort study assessed its real-world use and survival outcomes.
研究背景：
Sacituzumab govitecan（SG）在法国获准作为三线治疗用于转移性三阴性乳腺癌 （mTNBC）及激素受体阳性/HER2 阴性（HR+/HER2–mBC）转移性乳腺癌的早期使用。本项全国性队列研究评估了其真实世界的使用情况及生存结局。
Methods:
Using the French National Health Data System, we included all patients initiating SG between July 1, 2021, and December 31, 2023, with follow-up until June 30, 2024. Patient demographics, comorbidities, and prior treatments were recorded. Overall survival (OS) and time to treatment discontinuation (TTD) were estimated by Kaplan-Meier methods, and multivariable Cox models identified OS prognostic factors.
研究方法：
基于法国国家健康数据系统，纳入 2021 年 7 月 1 日至 2023 年 12 月 31 日期间开始使用 SG 的所有患者，随访至 2024 年 6 月 30 日。记录患者人口学特征、合并症及既往治疗。 采用Kaplan-Meier方法估算总生存期（OS）及治疗中止时间（TTD），并通过多变量 Cox 模型识别 OS 预后因素。
Results:
3653 patients were included: 2527 mTNBC and 1,126 HR+/HER2– mBC, with median ages of 58 and 61.5 years. Median OS was 11.0 months (95%CI: 10.4–11.7) for mTNBC and 11.4 months (95% CI: 10.7–12.4) for HR+/HER2–mBC. One-year survival was 47% and 48% and median TTD of 4.3 and 3.5 months, respectively. Poorer OS was independently associated with inpatient SG initiation and liver/digestive metastases. In mTNBC, additional factors included brain metastases, respiratory disease, tobaccorelated hospitalisation, multiple metastatic sites, and prior treatments.
研究结果：
共纳入 3,653 例患者：其中 2,527 例 mTNBC，1,126 例 HR+/HER2–mBC，中位年龄分别为 58 岁和 61.5 岁。mTNBC 的中位 OS 为 11.0 个月（95% CI：10.4–11.7），HR+/HER2–mBC 为 11.4 个月（95%CI ：10.7–12.4）。一年生存率分别为 47% 和 48%，中位 TTD 分别为 4.3 个月和 3.5 个月。OS 较差的独立相关因素包括住院期间开始 SG 治疗及肝/消化道转移；在 mTNBC 中，其他因素还包括脑转移、呼吸系统疾病、与烟草相关的住院史、多部位转移及既往治疗。
Conclusions:
The study highlights SG’s clinical relevance and the challenge of translating trial efficacy into real-world outcomes, reinforcing the need for further investigation of tolerability in broader populations.
研究结论：
该研究强调了 SG 的临床相关性，同时指出将临床试验疗效转化为真实世界结局的挑战，进一步凸显在更广泛人群中探索其耐受性的必要性。
4.Pathway activity profiling can predict neoadjuvant endocrine therapy response in HR+ HER2- postmenopausal early stage breast cancer
通路活性分析可预测 HR+ HER2- 绝经后早期乳腺癌患者的新辅助内分泌治疗反应
（Breast Cancer Research ，IF=6.10 ）
Abstract：
Background:
To improve patient selection for neoadjuvant endocrine therapy (NET), signal transduction pathway profiles of estrogen receptor (ER)-, androgen receptor (AR), were studied and compared to standard immunohistochemistry (IHC) in postmenopausal patients with HR+ (IHC ER≥50%, progesterone receptor any), HER2- breast cancer of the NEOLBC trial (NCT03283384).
研究背景：
为改善新辅助内分泌治疗（NET）患者的选择，本研究分析并比较了雌激素受体（ER）、 雄激素受体（AR）信号转导通路活性谱与标准免疫组化（IHC）在 NEOLBC 试验 （NCT03283384）中 HR+（IHC ER≥50%，孕激素受体任意）、HER2- 绝经后乳腺癌患者中的表现。
Methods:
After two weeks of NET with letrozole, patients with Ki67 (Ki67-2W)≥1% IHC were randomized to receive letrozole + ribociclib or standard chemotherapy until surgery, while patients with Ki67-2W <1% continued NET (letrozole monotherapy). Baseline, two week- and resection FFPE samples of 82 patients were analyzed using mRNA-based OncoSIGNal profiling test, providing the pathway activity score (PAS).
研究方法：
患者接受来曲唑（letrozole）NET 两周后，若 Ki67（Ki67-2W）≥1%（IHC），则随机分配至 来曲唑 + ribociclib 或标准化疗直至手术；若 Ki67-2W <1%，则继续 NET（来曲唑单药）。共收集 82 例患者的基线、两周及切除 FFPE 样本，采用基于 mRNA 的 OncoSIGNal 通路活性分析，获得通路活性评分（PAS）。
Results:
Despite samples being ER-IHC ≥50%, the ER-PAS varied over a range of 32 - 78 (scale from 0 – 100) with 20% of the patients showing low ER-PAS (32 – 45; similar to triple negative breast cancer tissue). At 2 weeks, 89% (73/82) of the patients showed a decreased ER-PAS (11.6 ± 8.6) compared to baseline (p<0.001), whereas ER-IHC remained unchanged. Patients with complete response (RECIST1.1) appeared to have a higher ER-PAS at baseline compared to those with stable disease (p = 0.03), ROC analysis confirmed ER-PAS at baseline as an acceptable predictive factor for MRI response (AUC ≥ 0.7). Lastly, baseline and 2-week pathway activity profiling could identify targetable escape mechanisms for NET non-responders, which could improve personalized treatment strategies.
研究结果：
尽管样本 ER-IHC ≥50%，ER-PAS 范围差异较大（32–78，评分范围 0–100），其中 20% 患者 ER-PAS 偏低（32–45，类似三阴性乳腺癌组织）。两周后，89%（73/82）患者 ER-PAS 较基线显著下降（平均下降 11.6 ± 8.6，p<0.001），而 ER-IHC 未见变化。完全缓解（RECIST1.1）患者基线 ER-PAS 高于疾病稳定者（p=0.03），ROC 分析证实基线 ER-PAS 对 MRI 反应预测具有可接受的准确性（AUC ≥0.7）。此外，基线及两周的通路活性分析可识别 NET 无反应患者的可靶向逃逸机制，有助于优化个体化治疗策略。
Conclusions:
ER IHC+ does not correlate to ER-PAS and ER-PAS is a more dynamic marker that appears to reflect variable NET response more accurately than IHC.
研究结论：
ER IHC 阳性并不等同于 ER-PAS，ER-PAS 是更具动态性的指标，较 IHC 更能准确反映 NET 反应差异。
5. Breast cancer staging for patients with “low‐risk” disease: Are they all the same？
低危乳腺癌患者的分期：他们是否都一样？
（Cancer，IF=5.10 ）
Abstract：
Background:
Contemporary breast cancer staging incorporates anatomic and biologic factors. Although a low (<11) Oncotype Recurrence Score (RS) is linked to favorable survival, it is unclear if RS alone justifies downstaging to pathologic prognostic stage (PPS) IA. This study evaluated whether a low RS equates prognostically to PPS IA.
研究背景：
目前乳腺癌分期结合了解剖学因素和生物学因素。尽管较低的 Oncotype 复发评分（Recurrence Score，RS <11）与良好的生存预后相关，但目前尚不清楚仅凭 RS 是否足以将分期降至病理预后分期（Pathologic Prognostic Stage，PPS）IA。本研究旨在评估低 RS 在预后上是否等同于 PPS IA。
Methods:
Patients (18–75 years) with pT1–3/pN0–1/M0, hormone receptor– positive, HER2-negative unilateral invasive breast cancer, diagnosed between 2010 and 2018 were identified from the National Cancer Database. Patients receiving neoadjuvant therapy or lacking RS data were excluded. Patients were grouped by PPS, with overall survival (OS) estimated using Kaplan–Meier and adjusted with Cox models.
研究方法：
从国家癌症数据库中筛选出在 2010 至 2018 年间确诊的患者，这些患者年龄在 18–75 岁，患有 pT1–3/pN0–1/M0、激素受体阳性（hormone receptor–positive）、HER2 阴性（HER2-negative）单侧浸润性乳腺癌。接受新辅助治疗或缺乏复发评分（Recurrence Score，RS）数据的患者被排除。患者根据病理预后分期（Pathologic Prognostic Stage，PPS）进行分组，并采用 Kaplan–Meier 法估计总体生存（Overall Survival， OS），并通过 Cox 回归模型进行调整。
Results:
Among 231,031 patients, 23.8% had RS < 11, 36.6% had RS 11–17, 25.8% had RS18–25, and 13.8% had RS > 25. Median follow up was 58.9 months. Most with RS < 11 were PPS IA (94.2%), yet OS declined with higher stage (p < .001). Adjusted analyses showed worse OS for higher stages within RS < 11 (IB: HR 1.66 [95% CI, 1.34–2.05]; IIA: HR 2.29 [1.44–3.65]; IIB: HR 2.48 [1.03–5.95]). In the RS 11–17 group, 90.8% were PPS IA. Five‐year OS varied (IA: 97.8%, IB: 95.8%, IIA: 95.2%, IIB: 93.7%, IIIA: 100%; p < .001). Adjusted OS differences persisted (IB: HR 1.51 [1.32–1.73]; IIA: HR 1.32 [1.01–1.72]; IIB: HR 1.58 [0.95–2.63]; IIIA: HR 1.44 (0.21–9.95]).
研究结果：
在 231,031 名患者中，23.8% 的 RS < 11，36.6% 的 RS 为 11–17，25.8% 的 RS 为 18-25，13.8% 的 RS > 25。中位随访时间为 58.9 个月。大多数 RS < 11 的患者属于 PPS IA （94.2%），然而，随着分期升高，总体生存率（OS）下降（p < 0.001）。调整分析显示，在 RS < 11 的患者中，较高分期的 OS 更差（IB：HR 1.66 [95% CI，1.34–2.05]； IIA：HR 2.29 [1.44–3.65]；IIB：HR 2.48 [1.03–5.95]）。在 RS 11–17 组中，90.8% 属于 PPS IA。5 年 OS 随分期不同而变化（IA：97.8%，IB：95.8%，IIA：95.2%，IIB： 93.7%，IIIA：100%；p < 0.001）。调整后 OS 差异仍然存在（IB：HR 1.51 [1.32–1.73]；IIA：HR 1.32 [1.01–1.72]；IIB：HR 1.58 [0.95–2.63]；IIIA：HR 1.44 [0.21–9.95]）
Conclusions:
Prognostic stage significantly influences survival among patients with low RS. RS < 11 alone should not automatically downstage patients to PPS IA; anatomic and other nongenomic factors remain important for prognosis.
研究结论：
预后分期对低 RS 患者的生存具有显著影响。仅凭 RS < 11 不应自动将患者降至病理预后分期（PPS）IA；解剖学因素及其他非基因组因素在预后评估中仍然具有重要作用。
6. Survival Outcomes With or Without Risk-Reducing Mastectomy in BRCA1 and BRCA2 Pathogenic Variant Carriers
BRCA1和BRCA2致病性突变携带者接受或不接受降低风险乳房切除术的生存结局
（Breast Cancer ，IF=2.90 ）
Abstract：
Background:
Many women carrying pathogenic variants (pvs) of BRCA1 and BRCA2 genes (pvBRCA1/2) elect to undergo bilateral risk-reducing mastectomy (BRRM) in the belief that it will improve their overall survival (OS). Although many are satisfied with their decision to undergo BRRM a significant minority exhibit regret. We compared long-term oncology outcomes in women with pvBRCA1/2 choosing BRRM with those choosing a program of imaging surveillance.
研究背景：
许多携带BRCA1和BRCA2基因致病性变异（pvBRCA1/2）的女性选择接受双侧降低风险乳房切除术（BRRM），认为这将改善其总生存期（OS）。尽管多数女性对接受BRRM的决定感到满意，但仍有相当一部分人表现出后悔情绪。我们比较了选择BRRM与选择影像学监测方案的pvBRCA1/2女性携带者的长期肿瘤学结局。
Methods:
All participants were attendees at a regional family history/genetics service and had undergone genetic testing for pvBRCA1/2. Carriers of pvBRCA1/2 elected either to undergo BRRM or imaging surveillance as directed by UK national guidance. A prospective cohort design examined OS, breast cancer–specific death, and breast cancer incidence between the study groups.
研究方法：
所有患者均为当地接受家族史/遗传学服务的就诊者，并已接受pvBRCA1/2的基因检测。 pvBRCA1/2 携带者根据英国国家指南选择接受BRRM或影像学监测。采用前瞻性队列设计，比较研究组间的OS、乳腺癌特异性死亡和乳腺癌发病率。
结果：共有460名女性选择接受BRRM，745名选择监测（中位年龄分别为37.2岁和38.5岁；P = .06）。BRRM后总随访时间为4,652人年。乳腺癌总年发病率为2.4%，BRRM后降至0.15%，较单纯监测降低94%（对数秩检验χ² = 86.1；P < .001）。BRRM时诊断出9例隐匿性癌症（2%）。BRRM组和监测组的乳腺癌特异性死亡相似（分别为2例和4例死亡；P = .36；随访时间分别为4,634和5,419人年）。两组中乳腺癌死亡与卵巢癌死亡的比例相似。
Results:
A total of 460 women elected to undergo BRRM, while 745 chose surveillance (median age, 37.2 years and 38.5 years, respectively; P 5 .06). Follow-up totaled 4,652 woman-years after BRRM. Overall annual incidence rate of breast cancer was 2.4%, falling to 0.15% after BRRM, a 94% reduction compared with surveillance alone (log-rank chi-square 5 86.1; P < .001). There were nine occult cancers diagnosed at BRRM (2%). Breast cancer–specific deaths were similar in the BRRM and surveillance groups (two and four deaths, respectively; P 5 .36; 4,634 and 5,419 woman-years of follow-up, respectively). Proportionately, deaths from breast cancer were similar to deaths from ovarian cancer in both treatment groups.
研究结果：
共有 460 名女性选择接受双侧风险降低乳房切除术（BRRM），而 745 名女性选择监测（中位年龄分别为 37.2 岁和 38.5 岁，P = 0.06）。BRRM 后的随访总计 4,652 人年。乳腺癌的总体年发病率为 2.4%，在 BRRM 后降至 0.15%，与单纯监测相比降低了 94%（log-rank 卡方 = 86.1；P < 0.001）。在 BRRM 时共诊断出 9 例隐匿性癌症（2%）。乳腺癌特异性死亡在 BRRM 组和监测组相似（分别为 2 例和 4 例，P = 0.36；随访时间分别为 4,634 和 5,419 人年）。在两组中，乳腺癌死亡比例与卵巢癌死亡比例相近。
Conclusions:
For women electing imaging surveillance over risk-reducing surgery, our results may offer reassurance that their breast cancer–specific survival and OS are unlikely to be compromised. However, breast cancer incidence rates are significantly reduced after BRRM compared with imaging surveillance, which may be important information for women with pvBRCA1/2 considering BRRM.
研究结论：
对于选择影像学监测而非风险降低手术的女性，我们的结果可能带来一定安慰，即她们的乳腺癌特异性生存率和总生存率（OS）不太可能受到影响。然而，与影像学监测相比，接受双侧风险降低乳房切除术（BRRM）后乳腺癌的发病率显著降低，这对于携带 BRCA1/2 致 病性变异（pvBRCA1/2）并考虑 BRRM 的女性而言可能是重要的信息。
