Impact of germline mutations on the development of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL) in women with textured breast implants

种系突变对有纹理乳房植入物的女性发生乳房植入物相关间变性大细胞淋巴瘤 (BIA-ALCL) 的影响

• 批准号: 10685505
• 负责人: Paola Ghione
• 金额: $ 8.85万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-17 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10685505
• 关键词: Age; Awareness; BRCA mutations; Breast Cancer Patient; Cancer-Predisposing Gene; Case Study; Cessation of life; Characteristics; Classification; Clinical; Collection; Communication; DNA; Data; Data Set; Decision Making; Development; Devices; Disease; Evaluation; Excision; Exclusion; Exposure to; Future; General Population; Germ-Line Mutation; Global Awareness; Grant; Hereditary Malignant Neoplasm; High Prevalence; High Risk Woman; Implant; Incidence; Infiltration; Internal Breast Prosthesis; Journals; Ki-1 Large-Cell Lymphoma; Length; Liquid substance; Literature; Lymphoma; Lymphomagenesis; Malignant Neoplasms; Malignant lymphoid neoplasm; Malignant neoplasm of ovary; Mammaplasty; Manufacturer; Marketing; Mastectomy; Memorial Sloan-Kettering Cancer Center; Methods; Mutation; Nature; Netherlands; Operative Surgical Procedures; Patients; Persons; Physicians; Plastic Surgical Procedures; Population; Predisposition; Prevalence; Procedures; Prospective cohort; Publishing; Radiation therapy; Reconstructive Surgical Procedures; Records; Relative Risks; Reporting; Rest; Risk; Risk Assessment; Risk Estimate; Risk Factors; Role; Sales; Saline; Silicones; Surface; Surgeon; T-Cell Lymphoma; Testing; Texture; Tissues; United States Food and Drug Administration; Update; Woman; World Health Organization; breast surgery; capsule; chemotherapy; cohort; comparison group; epidemiology study; follow-up; high risk; improved; insight; lymph nodes; malignant breast neoplasm; mutational status; reconstruction; risk prediction; targeted sequencing; tumor

Breast implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma that arises as a fluid collection or mass near textured breast implants. The lymphoma is usually confined to the fluid surrounding the implants or to the capsule, a fibrous tissue around the implants, but in 10-20% of the cases, it can spread to lymph nodes or present as an infiltrating mass. BIA-ALCL is treated successfully with implant removal and capsulectomy in most patients, but ~20% require chemotherapy and/or radiotherapy. Since the first description of BIA-ALCL in 1997, 733 total unique cases have been reported, with 36 patient deaths, leading to warning communications from the FDA in 2011 and 2016, and ultimately, to the recall from the market of textured implants produced by one of the most popular manufacturers in 2019. Global awareness of this disease was thus increased, leading to improved identification and reporting of cases, as well as to an urgent need for risk prediction for women with implants in place, currently estimated to be 10s of millions worldwide. Although some women choose to remove the implants, the risk of getting BIA-ALCL from exposure to textured implants is low and could be related to specific variables that remain largely unknown. Our collaborative group through Memorial Sloan Kettering Cancer Center (MSKCC) has reported the incidence of BIA-ALCL in a cohort of more than 3500 women with textured breast implants followed long term after surgery for breast cancer (BC). In this cohort, the Cordeiro Cohort, unique in its nature, 11 patients developed BIA- ALCL after an exposure of 7-10 years. This is the highest incidence described so far in the literature, however no particular variable (related to the type of BC, exposure to chemo or radiation therapy, filling of the implants with saline or silicone) was related to higher risk of lymphoma. Our collaborators from the Netherlands Cancer Institute have recently reported preliminary data suggesting BRCA mutations might be more frequent in BIA- ALCL cases than in the rest of the population. Within our cohort of 3500 women with implants followed long term, many patients were tested for BRCA mutations and/or were included in the MSK-IMPACT study, a broad tumor targeted sequencing effort that included the analysis of normal DNA to filter out germline mutations from the tumor results. This unusual and absolutely unique combination of studies conducted on this population may allow us to determine if BRCA and other germline mutations are related to lymphomagenesis in people with breast implants, and the relative risk of women with germline mutations to develop BIA-ALCL. This in turn will inform decision making for women with implants and their physicians on procedures such as textured implant removal and reconstruction after mastectomy for women at higher risk of lymphoma. The identification of germline mutations that might be related to lymphomagenesis will lead to future grant submissions and evaluations of these mechanisms in other lymphoma subtypes, thus representing a milestone in our approach to the disease.

乳房植入物相关的间变性大细胞淋巴瘤 (BIA-ALCL) 是 T 细胞淋巴瘤的一种亚型， 表现为有纹理的乳房植入物附近的液体聚集或肿块。淋巴瘤通常局限于液体 围绕植入物或胶囊，植入物周围的纤维组织，但在 10-20% 的情况下，它 可扩散至淋巴结或表现为浸润性肿块。植入物成功治疗 BIA-ALCL 大多数患者需要切除和囊切除术，但约 20% 需要化疗和/或放疗。 自 1997 年首次描述 BIA-ALCL 以来，已报告了 733 例独特病例，其中 36 名患者 死亡，导致 FDA 在 2011 年和 2016 年发出警告通讯，并最终导致召回 2019 年最受欢迎的制造商之一生产的纹理植入物市场。全球知名度 因此，这种疾病的发病率有所增加，从而改善了病例的识别和报告，并提高了 迫切需要对植入假体的女性进行风险预测，目前估计有数千万 全世界。尽管有些女性选择移除植入物，但暴露后罹患 BIA-ALCL 的风险 对纹理植入物的影响较低，可能与很大程度上仍未知的特定变量有关。我们的 纪念斯隆凯特琳癌症中心 (MSKCC) 合作小组报告了 BIA-ALCL 在超过 3500 名植入纹理乳房植入物的女性中进行了术后长期随访 用于乳腺癌（BC）。在这个队列中，Cordeiro 队列性质独特，有 11 名患者出现了 BIA- 暴露 7-10 年后的 ALCL。然而，这是迄今为止文献中描述的最高发生率 无特定变量（与 BC 类型、接受化疗或放疗、植入物填充有关） 盐水或硅胶）与淋巴瘤风险较高有关。我们来自荷兰癌症中心的合作者 研究所最近报告的初步数据表明，BRCA 突变在 BIA 患者中可能更为频繁。 ALCL 病例数高于其他人群。在我们的 3500 名接受假体植入的女性队列中进行了长期随访 术语中，许多患者接受了 BRCA 突变检测和/或被纳入 MSK-IMPACT 研究，这是一项广泛的研究 肿瘤靶向测序工作包括分析正常 DNA 以过滤掉种系突变 肿瘤结果。这种针对这一人群进行的不寻常且绝对独特的研究组合可能会 让我们能够确定 BRCA 和其他种系突变是否与患有淋巴瘤的人的淋巴瘤发生有关 乳房植入物，以及具有种系突变的女性患 BIA-ALCL 的相对风险。这反过来又将 为植入假体的女性及其医生提供有关纹理假体等手术的决策信息 对于淋巴瘤风险较高的女性，乳房切除术后的切除和重建。鉴定 可能与淋巴瘤发生有关的种系突变将导致未来的拨款申请和 对其他淋巴瘤亚型中的这些机制进行评估，从而代表了我们方法的一个里程碑 对疾病。