ImportanceAmong women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC.ObjectiveTo estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC.Design, Setting, and ParticipantsParticipants were enrolled in the Young Women’s Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023.Main Outcomes and MeasuresThe 5- and 10- year cumulative incidence of SPBC.ResultsIn all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70).ConclusionsFindings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

中文翻译：

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年轻乳腺癌幸存者中的第二原发乳腺癌

重要性在 40 岁或以下被诊断患有原发性乳腺癌 (BC) 的女性中，先前的数据表明，她们患第二原发性乳腺癌 (SPBC) 的风险高于年龄较大的女性患上第一原发性乳腺癌的风险。估计年轻 BC 患者中 SPBC 的累积发病率并描述其危险因素。设计、环境和参与者参与者参加了年轻女性乳腺癌研究，这是一项前瞻性研究，纳入了 1297 名 40 岁或以下、被诊断为 0 至 III 期的女性BC 省，从 2006 年 8 月到 2015 年 6 月。通过患者调查和病历审查收集人口统计、基因检测、治疗和结果数据。在确定 SPBC 累积发生率时，使用事件时间分析来解释竞争风险，并使用细灰色次分布风险模型来评估临床因素与 SPBC 风险之间的关联。数据分析时间为 2023 年 1 月至 5 月。 主要结果和措施 SPBC 的 5 年和 10 年累积发病率。结果 总共 685 名患有 0 至 III 期 BC 的女性（原发 BC 诊断时的平均 [SD] 年龄为 36 [4]年）接受单侧乳房切除术或肿瘤切除术作为 BC 主要手术的患者均纳入分析。在中位 (IQR) 10.0 (7.4-12.1) 年随访中，17 名患者 (2.5%) 出现 SPBC；其中 2 名患者在肿瘤切除术后同侧乳房出现癌症。从原发 BC 诊断到 SPBC 的中位时间 (IQR) 为 4.2 (3.3-5.6) 年。在 577 名接受基因检测的女性中，未携带致病性变异的女性（544 名女性中的 12 名）的 10 年 SPBC 风险为 2.2%，而携带致病性变异的女性（33 名中的 3 名）的 10 年 SPBC 风险为 8.9%。在多变量分析中，PV 携带者与非携带者相比，SPBC 的风险较高（次分布风险比 [sHR]，5.27；95% CI，1.43-19.43），原发性原位 BC 女性与侵袭性 BC 女性相比（sHR，5.61；95%） CI, 1.52-20.70)。结论该队列研究的结果表明，没有种系致病性变异的年轻 BC 幸存者在诊断后的前 10 年内发生 SPBC 的风险较低。种系基因检测的结果可能会为该人群的治疗决策和后续护理考虑提供信息。