Sokolenko Anna, Gorodnova Tatiana, Enaldieva Diana, Shestakova Anna, Ivantsov Alexandr, Nyuganen Anna, Berlev Igor, Krivorotko Petr, Belyaev Alexey, Imyanitov Evgeny
Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 Saint-Petersburg, Russia.
Department of Medical Genetics, St.-Petersburg State Pediatric Medical University, 194100 Saint-Petersburg, Russia.
Explor Target Antitumor Ther. 2025 Jun 18;6:1002325. doi: 10.37349/etat.2025.1002325. eCollection 2025.
/-associated breast and ovarian carcinomas are often regarded as a single entity, assuming that and genes are almost equivalent with regard to their clinical significance. However, and genes differ in their function; therefore, a comparison of treatment outcomes in vs. carriers is warranted.
This study focused on consecutive patients treated with neoadjuvant chemotherapy (NACT), given that these subjects are treatment-naive and accessible for immediate assessment of pathological and clinical outcomes.
-associated high-grade serous ovarian carcinomas (HGSOCs) demonstrated significantly higher rates of pathologic complete response (pCR) as compared to -related cancers [8/15 (53%) vs. 7/48 (15%), = 0.004]. In contrast, HER2-negative breast cancer (BC) patients showed a numerically higher rate of pCR in vs. mutation carriers [38/69 (55%) vs. 13/36 (36%), = 0.1]. However, the comparison with wild-type (WT) tumors revealed that this tendency was mainly attributed to the increased prevalence of hormone receptor (HR)-negative disease in the former group. When BC patients were stratified according to the tumor receptor status, the response rates in triple-negative patients were consistently higher than in HR+/HER2- patients across all analyzed subgroups [: 35/59 (59%) vs. 3/10 (30%); : 5/10 (50%) vs. 8/26 (31%); WT: 31/76 (41%) vs. 12/74 (16%); Mantel-Haenzsel < 0.001]. Logistic regression analysis revealed that the odds ratio (OR) for achieving pCR was higher for receptor status (triple-negative vs. HR+: OR = 3.4, 95% CI 1.9-6.0, < 0.001) than for status (any mutation vs. WT: OR = 2.1, 95% CI 1.2-3.6, = 0.008). The addition of carboplatin did not improve pCR rates in - or -associated BCs, while there was a numerically higher efficacy of carboplatin-containing regimens in patients with WT triple-negative tumors [14/26 (54%) vs. 15/44 (34%), = 0.13].
Hereditary ovarian carcinomas demonstrate better NACT outcomes in vs. mutation carriers. The opposite trend is observed in BC, which is likely to be attributed to a high frequency of triple-negative disease in - but not -associated BCs. Triple-negative receptor status rather than / status is the strongest predictor of response to NACT in BC.
BRCA1和BRCA2相关的乳腺癌和卵巢癌通常被视为一个单一实体，假定BRCA1和BRCA2基因在临床意义上几乎等同。然而，BRCA1和BRCA2基因在功能上存在差异；因此，有必要比较BRCA1与BRCA2携带者的治疗结果。
本研究聚焦于接受新辅助化疗（NACT）的连续患者，因为这些受试者未接受过治疗且便于立即评估病理和临床结果。
与BRCA2相关的高级别浆液性卵巢癌（HGSOC）相比，BRCA1相关癌症的病理完全缓解（pCR）率显著更高[8/15（53%）对7/48（15%），P = 0.004]。相比之下，HER2阴性乳腺癌（BC）患者中，BRCA1突变携带者的pCR率在数值上高于BRCA2突变携带者[38/69（55%）对13/36（36%），P = 0.1]。然而，与野生型（WT）肿瘤比较显示，这种趋势主要归因于前一组中激素受体（HR）阴性疾病患病率的增加。当根据肿瘤受体状态对BC患者进行分层时，在所有分析的亚组中，三阴性患者的缓解率始终高于HR+/HER2-患者[BRCA1：35/59（59%）对3/10（30%）；BRCA2：5/10（50%）对8/26（31%）；WT：31/76（41%）对12/74（16%）；Mantel-Haenzsel P<0.001]。逻辑回归分析显示，实现pCR的优势比（OR）对于受体状态（三阴性对HR+：OR = 3.4，95%CI 1.9 - 6.0，P<0.001）高于对于BRCA状态（任何突变对WT：OR = 2.1，95%CI 1.2 - 3.6，P = 0.008）。添加卡铂并未提高BRCA1或BRCA2相关BC的pCR率，而含卡铂方案在WT三阴性肿瘤患者中的疗效在数值上更高[14/26（54%）对15/44（34%），P = 0.13]。
遗传性卵巢癌中，BRCA1突变携带者的NACT结果优于BRCA2突变携带者。在BC中观察到相反的趋势，这可能归因于BRCA1相关而非BRCA2相关BC中三阴性疾病的高频率。三阴性受体状态而非BRCA1/2状态是BC中对NACT反应的最强预测因子。
