BACKGROUND The combination of FFDM and DBT can significantly improve the diagnostic efficiency of breast cancer, but with the increase of breast radiation absorbed dose. OBJECTIVES To compare and analyze the radiation dose and diagnostic performance of different mammography positions combinations of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) for different density types of breasts. METHODS This retrospective study involved 1,195 patients who underwent simultaneous breast DBT and FFDM. The mammography combinations were Group A, FFDM(CC+MLO); Group B, FDM(CC)+DBT(MLO); Group C, FFDM(MLO)+DBT(CC); Group D, DBT(CC+MLO); and Group E, FFDM(CC+MLO)+DBT(CC+MLO). An intergroup comparative analysis of radiation dose and diagnostic performance of different combinations of mammography positions for different breast density types was performed using the pathologic and 24-month follow-up results as the diagnostic basis. RESULTS Overall, 2,403 mammograms indicated 477 cases of non-dense breast tissues and 1,926 cases of dense breast tissues. Differences in the mean radiation dose for each non-dense and dense breast group were statistically significant. The areas under the diagnostic receiver operating characteristic (ROC) curves for the non-dense breast group were not statistically significant. In the dense breast group, the z-values were 1.623 (p = 0.105) and 1.724 (p = 0.085) for the area under the ROC curve in Group C compared with Groups D and E, respectively, and 0.724 (p = 0.469) when comparing Group D with Group E. The differences between the remaining groups were statistically significant. CONCLUSION Group A had the lowest radiation dose and no significant difference in diagnostic performance compared with the other non-dense breast groups. Group C had high diagnostic performance in the dense breast group considering the low radiation dose.
Luminal A型乳腺癌是恶性程度相对较低、预后相对良好的分型，其治疗方式和获益程度成为临床医师关注的重点问题。系统性辅助治疗是目前应用广泛的癌症治疗手段，能够提高进行根治性手术的机会和改善远期预后。针对Luminal A型乳腺癌，系统性辅助治疗的方案正在逐渐完善，临床应用最多且最有效的是内分泌治疗，其次是细胞毒化疗。本文主要对Luminal A型乳腺癌的内分泌治疗以及细胞毒化疗的研究进展、临床指南和现存问题进行了总结，期望能够为解决辅助治疗中的耐药及过度治疗问题提供一些新的研究思路，在分子生物学水平上寻找到改进治疗方案的方式，为Luminal A型的乳腺癌患者提供低成本、高收益的治疗选择。
乳腺癌严重危害女性健康，影像学检查是实现乳腺癌早期发现、早期诊断的重要手段。影像组学通过提取医学影像的高通量特征并进行定量分析，在乳腺癌研究领域得到了广泛应用。随着研究的深入，瘤周影像组学特征中蕴含的肿瘤微环境相关信息逐渐受到重视。近年来，研究者将瘤周影像组学特征纳入到乳腺癌相关影像组学研究中，并取得了较好的成果。本文旨在对瘤周影像组学在乳腺癌良恶性病变鉴别、分子标志物和分子分型、新辅助治疗疗效及淋巴结转移预测等方面的研究进展进行总结，从而为乳腺癌患者的精准治疗提供思路。
乳腺韧带样纤维瘤病(breast desmoid-type fibromatosis, BDF)是一种良性浸润性梭形细胞肿瘤，属于乳腺间叶性肿瘤，其特征是纤维母细胞/肌纤维母细胞分化和Wnt/β-catenin通路的激活[1]。BDF具有局部侵袭性生长的特征，术前临床和影像学检查易误诊为恶性肿瘤[2]。笔者报告了一例疑似乳腺癌的BDF，详细介绍了其乳腺超声、X线摄影和MRI表现，并结合文献复习报告如下，以期提高临床医师对该病的认识。
Breast cancer has become the most diagnosed cancer in the world. The prevention and treatment of breast cancer still faces great challenges. With the establishment of diagnosis and treatment model based on molecular subtyping of breast cancer and the development of new therapeutic drugs, the medical treatment of breast cancer has formed a mature system integrated of chemotherapy, targeted therapy, endocrine therapy and immunotherapy. Because of the large number of breast cancer patients in China and their distinctive clinical characteristics in oncogenesis and progression, it is important to develop new drugs and explore appropriate treatment approaches suitable for the Chinese population in order to improve the survival benefits and change treatment pattern. In recent years, Chinese clinicians have achieved significant breakthroughs in breast cancer treatment. This article has reviewed the noteworthy advancement of clinical research on breast cancer in China in the past year, aiming to provide guidance for standardized diagnosis and treatment of breast cancer.
三阴性乳腺癌(TNBC)是一种特殊类型的乳腺癌，约占乳腺癌的10%~21%，其临床表现和分子生物学特征有别于其他分子分型乳腺癌。TNBC的发病年龄相对年轻，其发生、发展可能与种族、遗传、妊娠、月经、用药、生活方式等因素有关。TNBC复发和转移率较高，预后较差，因其缺乏特异性分子靶点，临床治疗手段有限。本研究整理了TNBC的分子遗传学、流行病学和临床特征3个方面的文献进展，旨在为TNBC的临床诊疗提供参考依据。
研究发现乳腺组织中也存在特殊的微生物群，其组成与丰度可能随着乳腺疾病类型和病情进展情况而发生特异性变化。乳腺癌患者微生物群失调作为一个新的风险因素与乳腺癌发展过程密切相关，并且显示出作为预后和预测性生物标志物的巨大潜力。随着微生物研究逐渐深入到单菌功能分析层面，局部组织微生物群在微环境中的组成和代谢变化在肿瘤发生、发展过程中扮演重要角色。本文旨在总结近年研究成果，描述乳房组织定植的独特微生物群，比较乳腺癌组织、正常乳房组织以及非癌性良性病变的微生物群差异，分析这种生态失调在乳腺癌发病过程中的作用，以及对微环境免疫功能和代谢变化的影响。
Objective:To search for the related literature and summarize the best evidences for preventing and treating subcutaneous seroma after breast cancer surgery.Methods:Following the "PIPOST" model, we identified a question, constructed a search strategy and proposed the inclusion and exclusion criteria. Then we systematically searched the databases in Chinese (CNKI, Wanfang Data, CQVIP, CBM and Medlive) and English (PubMed, Embase, Web of Science, Cochrane Library, National Institute for Health and Care Excellence, Cumulative index to nursing and allied health literature, Joanna Briggs Institute Library, National Comprehensive Cancer Network and American Society of Breast Surgeons) for literature related to prevention and treatment of subcutaneous seroma after breast cancer surgery from the establishment to June 10, 2022. Two researchers, who had received evidence-based training, evaluated literature quality and extracted evidence independently.Results:A total of 23 articles were retrieved, consisting of 6 traditional reviews, 2 expert consensuses and 15 systematic reviews. We summarized 30 items of evidence and categorized them into 6 aspects: surgical skills, pharmacological treatment, drain management, flap fixation, postoperative exercises and fluid monitoring and removal.Conclusion:The summarized best evidence can provide guidance for preventing and treating subcutaneous seroma after breast cancer surgery. Healthcare professionals should consider real-world clinical settings and cautiously apply the summarized evidence in seroma treatment and nursing.
Objective:To analyze the diagnosis and treatment of diabetic mastopathy (DM) and summarize the characteristics of DM based on literature review.Methods:A retrospective analysis was performed in 52 patients with pathologically confirmed DM in Tianjin Cancer Hospital from September 2011 to June 2021. The clinical data of these patients were collected to analyze their clinical manifestations, imaging features and pathological results.Results:All patients were female, with the age of 62(59, 68) years. Fifty patients had diabetes (96.15%, 50/52), of which 94.00% (47/50) had type 2 diabetes. The follow-up period was 40.7 (22.5, 46.0) months. Palpable breast masses were observed in 51 patients (98.08%, 51/52), mostly with firmness, unclear border, no tenderness and poor mobility. Breast X-ray revealed indeterminate, localized and dense breast parenchyma in 38 patients(79.17%, 38/48), with benign calcifications or well-defined mass areas in some cases. The ultrasound manifestation of DM ranged from localized thickening of the glands to undefined masses, with uneven echoes, irregular shapes, and structural derangement. Most of them were at the grade of BI-RADS 4-5 (88.64%, 39/44). Breast MRI shows non-mass-type enhancement lesions, indicating the possibility of breast cancer. All patients underwent biopsy by tumor resection or aspiration. The pathological features were fibrosis of the breast stroma, accompanied by ductal inflammation and lobular inflammation, even lymphocyte infiltration in some cases. Lymphocyte or inflammatory cell infiltration were observed in 19 cases, which was significantly correlated with the comorbidity of other autoimmune diseases (P=0.007).Conclusions:DM was a rare benign breast lesion, with clinical and imaging manifestations similar to breast cancer. For patients with breast masses and diabetes, biopsy by tumor resection or aspiration is recommended for a clear histopathological diagnosis.
多肽疫苗是根据肿瘤抗原表位进行氨基酸序列合成，从而激发宿主的免疫应答，具有良好的安全性和耐受性。多肽疫苗是乳腺癌免疫治疗的新领域，其临床研究已经取得了一定的成果，但是，目前还没有多肽疫苗获得上市许可。本文回顾了截止2023年1月1日在ClinicalTrials.gov网站上注册的多肽疫苗临床试验，分析了多肽疫苗在乳腺癌治疗中的安全性、有效性。
乳腺癌是全球女性最常见的恶性肿瘤之一。术后辅助化疗可以降低肿瘤复发率，提高总生存率，是乳腺癌综合治疗中非常重要的组成部分。但化疗药物及化疗过程中为预防或减轻消化道反应使用糖皮质激素可以造成免疫功能受损，是机会性病原体感染的高危因素。耶氏肺孢子菌肺炎是一种机会感染性肺部真菌病，起病隐匿，进展迅速，预后差。本文介绍1例接受剂量密集型AC-T(阿霉素、环磷酰胺续贯多西他赛)辅助化疗方案的早期乳腺癌患者感染耶氏肺孢子菌致死亡病例，总结乳腺癌患者接受化疗有可能感染肺孢子菌肺炎(pneumocystis carinii pneumonia，PCP)的高危因素、早期诊断和临床救治经验。
Objective:To analyze the risk factors of lactational mastitis (LM) in primiparas and build a risk prediction model of nomogram.Methods:The clinical data of 186 primiparas who delivered their baby in our hospital from June 2021 to June 2022 were retrospectively analyzed, and the incidence of LM in primiparas was statistically analyzed. The logistic regression analysis was applied to find the risk factors of LM in primiparas. The R3.6.3 software was applied to construct the nomogram for predicting LM in primiparas, and the receiver operating characteristic (ROC) curve and calibration curve were used to verify the nomogram.Results:Among 186 primiparas in lactation period, 42 patients developed mastitis, with an incidence of 22.6% (42/186). Logistic regression analysis showed that breast trauma history (OR=9.470, 95%CI: 3.450-25.996, P<0.001), milk stasis (OR=8.734, 95%CI: 3.241-23.534, P<0.001), cracked nipple (OR=5.540, 95%CI: 1.949-15.743, P=0.001) and abnormal lingual frenulum in infants (OR=7.121, 95%CI: 2.673-18.975, P<0.001) were independent risk factors for LM in primiparas. The area under the ROC curve was 0.867 (95%CI: 0.804-0.930). The slope of calibration curve was close to 1 (goodness-of-fit test: χ2=7.910, P=0.341).Conclusion:The primiparas with breast trauma history, milk stasis, cracked nipples and infants with abnormal lingual frenulum are in high risk of LM. The nomogram based on these four factors can provide guidance for clinical prediction of LM in primiparas and implementation of corresponding interventions.
Objective:To investigate the application of single-port non-lipolysis fluorescence-guided laparoscopy in axillary sentinel lymph node biopsy (SLNB) of early breast cancer.Methods:We retrospectively collected the clinicopathologic data of 30 early breast cancer patients in the Department of Breast Surgery, Sixth Affiliated Hospital of South China University of Technology from June 2020 to May 2022. They all underwent axillary SLNB by indocyanine green and nanocarbon staining and single-port non-lipolysis fluorescence-guided laparoscopy through the lateral thoracic approach. The surgical parameters and postoperative complications were compared using t test, χ2 test and Fisher exact test. The detection rates of sentinel lymph nodes (SLNs) were compared between different staining methods by McNemar test and the pathological positivity rates of detected lymph nodes were compared by χ2 test.Results:All 30 patients successfully underwent axillary SLNB by single-port non-lipolysis fluorescence-guided laparoscopy. The operation time was (35.4±3.4) min. The operation time and total axillary drainage volume in patients with BMI >24.0 kg/m2 were significantly higher compared with the patients with BMI of 18.5~24.0 kg/m2[(37.36±9.45) min vs (30.29±6.15) min, t=2.480, P=0.019; (155.62±4.29) ml vs(132.53±7.65)ml; t=9.748, P<0.001]. There was no significant difference in intraoperative blood loss, extubation time and postoperative complications (t=-0.869, P=0.388; t=1.193, P=0.238; P=1.000). A total of 121 SLNs were detected in 30 patients, (4.89±1.73) nodes per person. Fifteen nodes were confirmed as pathologically positive SLNs(12.39%, 15/121). Among 121 detected SLNs, 106 were luminescent (indocyanine green-positive) and and 88 were stained (nanocarbon positive); the detection rates of two methods were 87.6% (106/121) and 72.7% (88/121), respectively, indicating a significant difference (P=0.013). Fifteen nodes were pathologically positive out of 106 luminescent SLNs, with a positive rate of 14.15% (15/106); 13 nodes were pathologically positive out of 88 stained SLNs, with a positive rate of 14.77% (13/88); there was no significant difference between the two (χ2=4.081, P=0.130). All 30 patients were followed up for median 15 months, and no recurrence or distant metastasis of breast cancer was observed.Conclusion:Single-port non-lipolysis fluorescence-guided laparoscopy for axillary SLNB of early breast cancer is clinically feasible, with few complications and high detection rate of SLNs, worth of clinical application.
在本次讲座中，陈莉教授主要介绍了以下三个方面的内容：(1)机器人手术/腔镜手术的安全性；(2)乳腺外科机器人手术和腔镜手术的异同；(3)机器人手术的未来趋势。首先，临床研究证据表明：接受乳腺微创手术和开放手术的患者长期生存结局一致，微创手术是安全的临床术式。机器人手术组的手术时间高于开放手术组，但并发症比较，差异无统计学意义，乳房外形满意度、身心满意度、性生活质量显著优于开放手术组。其次，对于小乳房和中等大小的乳房，机器人手术性价比高；对于肿块位于腺体中央且距离皮肤表面5 mm以上的早期乳腺癌，机器人手术适用性较好；对于腺体退化明显的乳房，优选腔镜手术，慎用机器人手术。陈教授指出：机器人手术价格昂贵，应严格控制适应证，不能把机器人当腔镜使用；对于机器人手术，术前就要关注乳房在X线和MRI上的整体结构，关注腺体/脂肪的比例。最后，陈教授总结了机器人手术的优点：机器人手术更省力，机械臂承担了力量，避免术者手指疼痛，尤其是在狭小空间，操作灵活度优于腔镜手术，在缝合补片时更有优势。目前，机器人手术应用于乳腺外科的局限性表现如下：缺少乳腺手术相关定制器械、进口机器人维修困难、学习曲线长、手术费用高等。综上所述，机器人乳腺手术是安全的技术创新，让远程手术和精准治疗成为可能。
免疫球蛋白G4相关疾病(immunoglobulin G4-related disease，IgG4-RD)是一种免疫介导的全身性疾病[1]，常见于1型自身免疫性胰腺炎(autoimmune pancreatitis 1，AIP-1)，其他可能受影响的器官包括泪腺、唾液腺、肺、肾、肝、胆管、后腹膜、乳房、主动脉、垂体和前列腺等[2,3]。IgG4-RD典型的病理表现为淋巴组织中浆细胞浸润、闭塞性静脉炎和席纹状纤维化[4]。IgG4-RD的临床表现多样，可表现为器官或组织的非特异性肿大，具体表现取决于疾病累及的部位，而疾病早期往往由于病理学诊断不易获得，导致该疾病诊断困难。本文报道3例以乳房腋窝区肿块为主要表现的IgG4-RD，并对这类患者的临床特征及处理经验进行总结。
Objective:To explore the biological function of long non-coding RNA (lncRNA) WAC antisense RNA1(WAC-AS1) in breast cancer and its impact on the prognosis of breast cancer based on the Cancer Genome Atlas (TCGA) and Gene Tissue Expression (GTE) databases.Methods:Based on the data of lncRNA WAC-AS1 expression in the TCGA and GTE databases, the expression of WAC-AS1 in breast cancer tissue was analyzed and compared with normal breast tissues. The breast cancer patients were divided into high expression group and low expression group according to the median value of WAC-AS1 expression. The OS, progression-free survival (PFS), disease-specific survival (DSS), DFS, and proportion of immune cells infiltrated in cancer tissues were compared between the two groups. WAC-AS1 related gene mutations were analyzed using the tumor somatic mutation detection tool VarScan. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were also performed to explore WAC-AS1-involved signaling pathways in breast cancer. Finally, weighted gene correlation network analysis (WGCNA) was performed and a clinical prognostic model was constructed in breast cancer. The receiver operating characteristic (ROC) curve and the calibration curve of 3-year and 5-year OS were used to evaluate the prediction efficiency and accuracy of the model. The expression of WAC-AS1 was detected by fluorescence-based quantitative real-time PCR in MCF-10A, MCF-7 and MDA-MB-231 cells.Results:(1) WAC-AS1 expression in breast cancer tissue was significantly higher compared with normal breast tissues [4.17 (3.91, 4.41) vs 3.70 (3.37, 4.09), Z=3.880, P<0.001]. (2) The median OS in WAC-AS1 high expression group and low expression group was 10.0 years and 17.2 years, respectively, indicating a significant difference (HR=1.680, 95%CI: 1.208-2.338, P=0.002). There was no significant difference in PFS, DSS and DFS between those two groups(HR=1.105, 95%CI: 0.798-1.529, P=0.548; HR=1.303, 95%CI: 0.846-2.008, P=0.230; HR=1.092, 95%CI: 0.711-1.678, P=0.687). In breast cancer tissues with high expression of WAC-AS1, 4 kinds of immune cells (naive B cells, CD8+ T cells, follicular helper T cells and activated dendritic cells) were increased, while resting CD4+ memory T cells and resting mast cells were decreased (all P<0.050). (3)The genes with the highest frequency of WAC-AS1 related mutations were TP53, PIKCA and TTN. (4) The results of GSVA and GSEV showed a positive correlation between WAC-AS1 and DNA repair, MYC target V2, MYC target V1, E2F target, and mTORC1 signaling pathway. (5) WGCNA analysis found that WAC-AS1 had the highest correlation with 91 genes related to small molecule biosynthesis in the yellow green module (r=0.270, P<0.001). (6) The results of univariate analysis showed that age (HR=1.034, 95%CI: 1.021-1.047, P<0.001), gender (female vs male, HR=1.388, 95%CI: 0.188-9.929, P=0.870), clinical stage (Phase Ⅱ vs Phase Ⅰ, HR=1.457, 95%CI: 1.043-2.022, P=0.017; Phase Ⅲ vs Phase Ⅰ, HR=4.022, 95%CI: 2.804-5.739, P<0.001; and Phase Ⅳ vs Phase I, HR=16.130, 95%CI: 9.413-27.630, P<0.001) and WAC-AS1 expression (HR=1.032, 95%CI: 1.005-1.061, P=0.020) were influencing factors for OS. Multivariate analysis showed that the expression of WAC-AS1 was correlated with OS in breast cancer patients (HR=1.377, 95% CI: 1.021-1.872, P=0.039). (7) The C-index of the constructed clinical prediction model was 0.759, the area under the ROC curve (AUC) was 0.626 (95%CI: 0.58.0-0.673, P<0.001), the sensitivity was 76.9%, and the specificity was 46.8%. The predicted curve fit well with the ideal curve. (8) The CT values of WAC-AS1 detected by PCR in three cell lines MCF-10A, MCF-7, and MDA-MB-231 were 32.39±0.10, 30.55±0.25, and 30.82±0.07, respectively, indicating a significant difference (F=30.310, P<0.001). Pairwise comparison showed that WAC-AS1 expression in MCF-7 and MDA-MB-231 cells was significantly higher than that in MCF-10A cells (t=7.916, 7.431, both P<0.001).Conclusions:The lncRNA WAC-AS1 is related to the tumor microenvironment and immune infiltration in breast cancer. The high expression of WAC-AS1 affects the prognosis of breast cancer pateints. WAC-AS1 may be a potential target and prognostic marker in breast cancer treatment.
在本次讲座中，刘淼教授首先回顾了乳腺癌外科手术范围从扩大到缩小的发展历程，讲解了乳腺淋巴引流途径，乳腺癌患者行腋窝淋巴结评估处理的意义和前哨淋巴结活组织检查的概念。然后，刘淼教授介绍了临床检查腋窝淋巴结阴性但前哨淋巴结阳性的乳腺癌患者的后续处理方案：根据Z0011临床研究结果，接受保留乳房手术的前哨淋巴结阳性患者可避免腋窝淋巴结清扫；若前哨淋巴结为微小转移且行乳房全切或保留乳房手术的患者可以避免腋窝淋巴结清扫；其余前哨淋巴结阳性且行乳房全切术的患者能否避免腋窝淋巴结清扫还有待进一步临床研究结果验证。对于临床检查腋窝淋巴结阳性的乳腺癌患者，刘淼教授推荐对术前超声引导下腋窝淋巴结穿刺活组织检查结果为阴性的患者进行前哨淋巴结活组织检查，避免腋窝淋巴结清扫。最后，刘淼教授重点介绍了上肢来源淋巴结和腋窝逆向淋巴结示踪在避免乳腺癌患者术后上肢淋巴水肿中的作用。
乳腺癌是全球女性最常见的恶性肿瘤，多基因检测使乳腺癌向着精准治疗的方向发展。国际上常用21基因检测、70基因检测作为早期乳腺癌患者辅助放射治疗和化疗决策的依据，但其对亚洲人群是否适用有待考证。28基因检测是基于亚洲数据的多基因检测模型。因此，本文对28基因检测在Luminal型早期乳腺癌患者中的应用进行综述。
Objective:To explore the potential factors related to the recurrence of benign and borderline breast phyllodes tumor (PT) and establish a nomogram to predict the recurrence rate of PT.Methods:The clinicopathological and imaging data of 65 patients with benign and borderline PT who were treated in Dongguan People’s Hospital from June 2016 to December 2019 were retrospectively analyzed. The univariate and multivariate logistic regression were used to analyze the independent risk factors for recurrence, and a nomogram was constructed accordingly. The receiver operating characteristics (ROC) curve was drawn and the area under the curve (AUC) was calculated. A calibration curve was established by bootstrap method to evaluate calibration performance. The clinical utility of this predictive model was demonstrated by decision curve analysis (DCA).Results:Univariate logistic regression analysis showed that the time interval between mass discovery and treatment (TIMDT)>6 months, uneven MRI enhancement pattern, ultrasonic findings(irregular shape, uneven edge, tumor lobulation, uneven internal echo, punctate strong echo, moderate/abundant blood flow signal and cystic structure) were related to PT recurrence (all P<0.050). Multivariate logistic regression analysis showed that TIMDT>6 months (OR=32.230, 95%CI: 2.343-443.367, P=0.009), uneven MRI enhancement pattern (OR=16.786, 95%CI: 1.030-273.431, P=0.048) and ultrasonic tumor lobulation (OR=14.861, 95%CI: 1.155-191.205, P=0.038) were independent risk factors for PT recurrence. A nomogram was constructed based on these three independent risk factors. The AUC of ROC was 0.906 (95%CI: 0.811-1.000), the sensitivity was 83.3% and the specificity was 88.7%. The calibration curve of the model showed a good calibration efficiency. The DCA curve displayed high clinical net benefit from predicting PT recurrence at a threshold of 0.04-0.96.Conclusion:The benign and borderline breast PT patients with the following features (TIMDT>6 months, uneven MRI enhancement pattern, and ultrasonic tumor lobulation) are in high risk of recurrence. The nomogram based on these three factors shows a strong ability to predict the recurrence of PT, indicating high potential in clinical application.
Objective:To evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting the prognosis of HER-2 positive breast cancer patients.Methods:We retrospectively analyzed the clinicopathological data of 176 patients with HER-2 positive breast cancer treated with neoadjuvant therapy (NAT) in the First Affiliated Hospital of Air Force Medical University from January, 2013 to June 2018. According to the pathological results of surgically removed specimens after NAT, the patients were divided into pCR group (n=84) and non-pCR group (n=92).Using the TIL counting method recommended by the international TIL working group, we assessed TIL level in the area between the borders of invasive tumor and adjacent normal tissues. The overall survival (OS) and recurrence-free survival (RFS) curves were plotted using the Kaplan-Meier method and the values were compared using log-rank test. The influencing factors of OS and RFS were analyzed by Cox proportional hazards regression model. The Mann-Whitney U test was used to analyze the change of TIL level before and after NAT.Results:(1) The TIL level before NAT (pre-TIL) presented a significant difference between pCR group and non-pCR group (χ2=12.140, P<0.001). (2) Survival analysis showed that pre-TIL was related to OS and RFS (OS: χ2=14.243, P<0.001; RFS: χ2=3.881, P=0.049). Subgroup analysis showed that pre-TIL was related to OS and RFS (OS: χ2=5.272, P=0.022; RFS: χ2=6.033, P=0.014) in non-pCR patients, while TIL level after NAT (post-TIL) was not related to OS and RFS (OS: χ2=0.174, P=0.677; χ2=0.074, P=0.786). The pre-TIL was significantly lower than post-TIL in 92 non-pCR patients [6.0% (5.0%, 25.0%) vs 30.0% (11.3%, 63.8%), Z=-5.474, P<0.001]. The change of TIL level before and after NAT in non-pCR was not significantly related to OS and RFS (OS: χ2=2.342, P=0.126; RFS: χ2=3.853, P=0.051). (3) The Cox univariate analysis showed that the patients with lower pre-TIL had lower OS (HR=2.556, 95%CI: 1.458-4.482, P=0.001), but pre-TIL was not related to RFS (HR=1.362, 95%CI: 0.996-1.862, P=0.053); multivariate analysis showed that pre-TIL was an independent factor of OS (HR=2.556, 95%CI: 1.458-4.482, P=0.001). Among the patients with non-pCR, the patients with low pre-TIL had lower OS (HR=1.878, 95%CI: 1.058-3.333, P=0.031) and RFS (HR=1.670, 95%CI: 1.090-2.559, P=0.019). Post-TIL was not significantly related to OS (HR=1.534, 95%CI: 0.202-11.673, P=0.679) and RFS (HR=0.905, 95%CI: 0.438-1.866, P=0.786) in patients with non-pCR. The change of TIL level before and after NAT was not an independent factor of OS(HR=3.020, 95%CI: 0.681-13.396, P=0.146) and RFS (HR=3.152, 95%CI: 0.939-10.576, P=0.063).Conclusion:Pre-TIL is a potential prognostic factor for HER-2 positive early breast cancer, and the predictive value of TIL change before and after NAT in non-pCR patients is worth of further exploration.
