Fernández-Abad María, Caniego-Casas Tamara, Carretero-Barrio Irene, Calderay-Domínguez Milagros, Saavedra Cristina, Hardisson David, Palacios José, Pérez-Mies Belén
Departments of Medical Oncology.
Pathology.
Am J Surg Pathol. 2025 Mar 1;49(3):294-302. doi: 10.1097/PAS.0000000000002351. Epub 2025 Jan 9.
Determining whether an ipsilateral breast carcinoma recurrence is a true recurrence or a new primary remains challenging based solely on clinicopathologic features. Algorithms based on these features have estimated that up to 68% of recurrences might be new primaries. However, few studies have analyzed the clonal relationship between primary and secondary carcinomas to establish the true nature of recurrences. This study analyzed 70 breast carcinomas from 33 patients using immunohistochemistry, FISH, and massive parallel sequencing. We compared 35 primary carcinomas with the associated recurrences, identifying 24 (68.6%) as true recurrences, 7 (20%) as new primaries, and 4 (11%) as undetermined. Twenty-eight primary carcinomas were invasive carcinomas (22 of no special type, 5 invasive lobular, and 1 invasive micropapillary carcinoma), and 7 were in situ (6 ductal and 1 lobular). Time to recurrence was longer for new primaries (median 12.8 y) than for true recurrences (median 6.8 y). Among the new primary cases, 6 of 7 (85%) patients had undergone mastectomy as their initial treatment. Clinicopathologic classifications of invasive carcinomas overestimated the number of new primaries (41.6% to 68.6%), partially due to phenotype conversion in 14% of true recurrences. Although 41.7% of recurrences showed private mutations or amplifications relevant to tumor progression, such as PIK3CA, PIK3R1, MAP3K1, AKT1, GATA3, CCND1, MDM4 , or T P 5 3 ; a common mutational progression pattern was not identified. Further studies, including larger series, are necessary to evaluate the prognostic significance of the molecular classification of recurrences.
仅基于临床病理特征来确定同侧乳腺癌复发是真正的复发还是新发原发性肿瘤仍然具有挑战性。基于这些特征的算法估计，高达68%的复发可能是新发原发性肿瘤。然而，很少有研究分析原发性和继发性癌之间的克隆关系以确定复发的真正性质。本研究使用免疫组织化学、荧光原位杂交（FISH）和大规模平行测序对33例患者的70例乳腺癌进行了分析。我们将35例原发性癌与其相关复发癌进行比较，确定24例（68.6%）为真正的复发，7例（20%）为新发原发性肿瘤，4例（11%）为无法确定。28例原发性癌为浸润性癌（22例非特殊类型，5例浸润性小叶癌，1例浸润性微乳头状癌），7例为原位癌（6例导管原位癌和1例小叶原位癌）。新发原发性肿瘤的复发时间（中位时间12.8年）比真正的复发时间（中位时间6.8年）更长。在新发原发性肿瘤病例中，7例患者中有6例（85%）最初接受了乳房切除术。浸润性癌的临床病理分类高估了新发原发性肿瘤的数量（41.6%至68.6%），部分原因是14%的真正复发存在表型转换。尽管41.7%的复发显示出与肿瘤进展相关的特有突变或扩增，如PIK3CA、PIK3R1、MAP3K1、AKT1、GATA3、CCND1、MDM4或TP53；但未发现常见的突变进展模式。需要进一步的研究，包括更大规模的系列研究，来评估复发分子分类的预后意义。
