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IMPORTANCE: Studies of the use of gonadotropin-releasing hormone analogs (GnRHa) to protect ovarian function have shown mixed results. OBJECTIVE: To determine whether administering GnRHa during chemotherapy in premenopausal women with breast cancer can reduce ovarian impairment. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted at the Shanghai Jiao Tong University Affiliated Shanghai Sixth People’s Hospital and Zhejiang Cancer Hospital in China, was an open-label trial involving premenopausal women aged 18 to 49 years with operable stage I to III breast cancer for which treatment with adjuvant or neoadjuvant cyclophosphamide-containing chemotherapy was planned in 2 parallel groups: treatment with chemotherapy with or without GnRHa. Enrollment occurred from September 2015 to August 2017, and follow-up ended December 2020. The data were analyzed in March 2021. A total of 405 patients were enrolled in the study, among whom 27 patients (6.7%) quit participation voluntarily, 33 (8.1%) did not meet the inclusion criteria and were excluded, and 15 (3.7%) were lost to follow-up. Ultimately 330 patients were included in the primary analysis, including 29 patients with baseline anti-Müllerian hormone levels less than 0.5ng/ mL. INTERVENTIONS: Eligible patients were randomly assigned (1:1) to receive chemotherapy with (n = 165) or without (n = 165) GnRHa. In patients randomized to receive GnRHa, 3.6 mg of goserelin or 3.75 mg of leuprorelin was injected subcutaneously once every 28 days from 1 to 2 weeks before the first cycle of chemotherapy to 4 weeks after the last cycle of chemotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was the rate of premature ovarian insufficiency (POI) at 12 months after chemotherapy. Premature ovarian insufficiency was defined as anti-Müllerian hormone levels of less than 0.5 ng/mL in this study. The secondary end point was overall survival (OS) and tumor-free survival (TFS). RESULTS: A total of 330 eligible patients could be evaluated with complete data, among whom 301 patients (91.2%; GnRHA group: mean [SD] age, 40.6 [6.7] years; control group: mean [SD] age, 40.2 [5.9] years) were eligible for primary end point analysis. At 12 months after the completion of chemotherapy, the POI rate was 10.3% (15 of 146) in the GnRHa group and 44.5% (69 of 155) in the control group (odds ratio, 0.23; 95% CI, 0.14-0.39; P

Axillary lymph node dissection is an indispensable step in modified radical mastectomy for breast cancer. It is the most reliable method and the golden standard to determine the status of axillary lymph nodes. It is also of great importance to evaluate the prognosis and develop treatment plans for breast cancer patients. Axillary lymph node dissection can be anatomically divided into levels I, II, and III. Level I and Level II axillary lymph dissection is the standard clinical treatment of axillary lymph nodes positive breast cancer, whereas level III axillary lymph node dissection has been controversial. Level III axillary lymph node metastasis is one of the important factors that can easily cause distant metastasis and recurrence. It is also an important index to estimate the prognosis of breast cancer patients. To facilitate the decision of whether or not to perform level III lymph node dissection, we reviewed the indications, complications, and surgical procedures of level III lymph node dissection.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid malignant tumors worldwide. Increasing investigations demonstrate that long non-coding RNAs (lncRNAs) expression is abnormally dysregulated in cancers. It is crucial to identify and predict the prognosis of patients for the selection of further therapeutic treatment. Methods: PDAC lncRNAs abundance profiles were used to establish a signature that could better predict the prognosis of PDAC patients. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a multi-lncRNA signature in the TCGA training cohort (N = 107). The signature was then validated in a TCGA validation cohort (N = 70) and another independent Fudan cohort (N = 46). Results: A five-lncRNA signature was constructed and it was significantly related to the overall survival (OS), either in the training or validation cohorts. Through the subgroup and Cox regression analyses, the signature was proven to be independent of other clinic-pathologic parameters. Receiver operating characteristic curve (ROC) analysis also indicated that our signature had a better predictive capacity of PDAC prognosis. Furthermore, ClueGO and CluePedia analyses showed that a number of cancer-related and drug response pathways were enriched in high risk groups. Conclusions: Identifying the five-lncRNA signature (RP11-159F24.5, RP11-744N12.2, RP11-388M20.1, RP11-356C4.5, CTC-459F4.9) may provide insight into personalized prognosis prediction and new therapies for PDAC patients.

e12548 Background: Pyroptosis is a type of inflammatory cell death mediated by gasdermins. Pyroptosis is critical for macrophage against pathogen infection. Recently growing evidences show that pyroptosis may affect development and progression of many cancers. We aim to explore the expression and related function of pyroptosis executioner Gasdermin D (GSDMD) in breast cancer. Methods: We investigated the expression level of GSDMD using TNM plotter and Breast Cancer landscape proteome with TCGA, GTEx and TARGET databases, and the prognostic value of GSDMD in invasive breast cancer using Kaplan-Meier plotter with TCGA, GEO and EGA databases. The treatment response prediction values of GSDMD in invasive breast were calculated using ROC-plotter with GEO database. Further validation of the prognostic value and chemotherapy response prediction value of GSDMD were carried out with immunohistochemical staining on tissues from 165 cases of breast cancer patients receiving neoadjuvant chemotherapy in our cancer center. Results: TNM plotter and breast cancer landscape proteome portal analysis shows that overall expression level of GSDMD in invasive breast cancer tissue is 1.67 folds higher than it is in breast normal tissues ( p=1.05*e-06). Expression of GSDMD in LuminalB subtype (p=0.019) and Her2 subtype(p=0.04) is significantly higher than it is in TNBC subtype. Calculations with Kaplan-Meier plotter show expression of GSDMD is negatively correlated with overall survival(OS), HR=0.61(0.4−0.95) p=0.027 and relapse free survival (RFS), HR =0.65(0.58−0.63), p=8.7*e-14 and distant metastasis free survival (DMFS) HR =0.75(0.61−0.91), p=0.0038 in breast cancer patients. ROC-plotter calculations show high GSDMD expression is a powerful endocrine therapy (AUC=0.731 p=6*e-09 ) and chemotherapy response (AUC=0.64 p=8*e-05 ) predictor based on 5-year RFS in overall breast cancer patients. Our IHC staining analysis shows consistent prognostic and chemotherapy prediction value of GSDMD expression in TNBC patients. Conclusions: In conclusion, our findings suggest that high expression of GSDMD is positively correlated with prognosis and therapeutic response in breast cancer. GSDMD is a promising prognostic marker and therapeutic response predictor in invasive breast cancer.

e16256 Background: Although pyroptosis is critical for macrophages against pathogen infection, its role in cancer cells remains elusive. GSDMC is a pyroptosis executioner newly identified in cancer cells and have been shown to facilitate inflammatory tumor death. However, the expression of GSDMC in Pancreatic Ductal Adenocarcinoma (PDAC), its prognostic significance and possible impact on reshaping tumor immune microenviroment in PDAC is still unknown. Methods: We investigated the expression level of GSDMC using TNM plotter with TCGA and GTEx databases, the prognostic value of GSDMC in PDAC using Kaplan-Meier plotter with TCGA, GTEx and TCGA databases. The correlations between GSDMC and immune infiltration in PDAC were calculated using TIMER2.0 and TIDE with TCGA database. We further validated the prognostic value of GSDMC with immunohistochemistry(IHC) staining on a tissue microarray of 172 cases of PDAC patients receiving treatment in our institution. Correlations between expression of GSDMC and tumor infiltration lymphacytes(TILs) cells were also analyzed on tissue samples of those 172 PDAC patients. Results: TNM plotter analysis shows that the expression of GSDMC in PDAC tumor tissue is 10.49 folds higher than it is in pancreatic normal tissues (p = 8.86*e-56). Results from Kaplan-Meier plotter analysis shows high expression of GSDMC is significantly correlated with poorer overall survival(OS), HR = 1.8(1.19−2.71) logrank P = 0.004 and shorter relapse free survival (RFS), HR = 4.6(1.94−10.88), Logrank P = 0.00014 in PDAC. Analysis with TIMER2.0 and TIDE platform shows that expression of GSDMC is positively correlated with immunosuppressive cells, Cancer Associated Fiberblast (CAF) and Meyloid Derived Tumor Suprresso Cells(MDTSC). IHC staining analysis results is also consistent with aformentioned bioinformatic analysis, showing that high GSDMC expression correlated with shorter OS and reduced Tils infiltration. Conclusions: Our findings suggest that high expression of GSDMC is related to poor prognosis and compromised immune cell infiltration in PDAC. GSDMC holds promise for serving as a valuable prognostic marker and therapeutic target in PDAC.

We report a 28-year-old woman who presented with a 6-year history of milk-like discharge from both of her nipples and was diagnosed with prolactinoma based on computed tomography (CT) findings and serum prolactin level. Further breast examination revealed a mass located in the upper outer region of the left breast. She underwent subtotal pituitary tumor resection. Thereafter, modified radical mastectomy was performed for left breast cancer. Twelve years after treatment, prolactinoma recurrence was detected, and bromocriptine therapy was administered. No recurrence of breast cancer was discovered. Based on this case report, we stress the importance of prolactin levels due to their possible biologic effects on breast cancer induction or growth.

Breast cancer is the cause for highest number of cancer-related death among women worldwide. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human breast cancer. Expression levels of ZFX were analyzed in 99 patients and four breast cancer cell lines. Lentivirus-mediated RNA interference was applied to silence ZFX expression, and the effects of ZFX knockdown on the growth of breast cancer cells were investigated. The immunohistochemical expression of ZFX was higher in more advanced tumor tissues. ZFX was also overexpressed in multiple breast cancer cell lines. Knockdown of ZFX inhibited cell proliferation and colony formation of MCF-7 and MDA-MB-231 cells. Moreover, ZFX silencing resulted in cell cycle arrest at G0/G1 phase. Depletion of ZFX decreased the phosphorylation level of AKT and increased the phosphorylation level of ERK2 and the expression of cyclin D1, which is involved in cell survival and cell cycle regulation. These findings suggest that ZFX plays an important role in breast cancer development and could be a potential therapeutic target for breast cancer.

Paired box 6 (PAX6) plays a significant role in the development of human neuroectodermal epithelial tissues. Previous studies have suggested that the PAX6 promoter is hypermethylated in breast cancer and that it is involved in breast cancer cell proliferation. The present study aimed to investigate the expression of PAX6 in invasive breast cancer tissues, and to evaluate its prognostic significance. Immunohistochemistry (IHC) was used to detect PAX6 expression on a breast cancer tissue microarray containing tissues from 111 patients. Associations of PAX6 expression with staging and prognosis were analyzed. PAX6 was mainly expressed in the nucleus. The PAX6 staining intensity was not associated with age, histological grade, lymph node status, tumor size, or progesterone receptor and human epidermal growth factor receptor 2 expression (all P>0.05). A high level of PAX6 staining was more frequent in estrogen receptor (ER)-negative cases compared with ER-positive cases (43.9 vs. 25.7%; P=0.049). After a median follow-up time of 110 months, the patients with low PAX6 expression exhibited an improved survival rate compared with the patients with high PAX6 expression (P