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Purpose To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. Methods In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. Results Of 44 enrolled patients (median age, 53.5 years; range, 34–69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3–4.1) and median OS was 15.0 months (95% CI 12.1–17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. Conclusion PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

Purpose To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. Methods The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. Results GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. Conclusion GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.

BackgroundGenetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes.MethodsWe collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations.ResultsThe median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02).ConclusionsThe most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.

Background: Androgen receptor (AR) blocker has become an increased interest in the treatment of BC, in which about 60-80% patients showed AR positive. However, currently no AR blocker has been approved in mBC. GT0918 is a new chemical entity of AR blocker with possible AR down-regulation. This study is an open-label, single-center, dose escalation phase I trial to assess GT0918 in mBC female patients who have progressed after systemic treatments in China. The primary objectives are to identify the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). The secondary objectives are to assess pharmacokinetics and pharmacodynamics of GT0918 with single and multiple dosage applications. (CTR20170757) Methods: Patients (pts) with historically confirmed mBC who had progressed after either chemotherapy, hormonal or targeted therapy, or could not tolerate currently standard therapies were eligible. With the starting dose at 100 mg of GT0918, the decision of dose escalation in the 3+3 design was based on the safety and tolerability assessments. GT0918 was administered orally once, followed by a 7-day off-treatment period for single dose PK analysis of drug elimination. Then GT0918 oral administration was resumed once daily for 28 consecutive days and multiple dose PK analysis was assessed at the end of first cycle (28 days). The first 28-days on treatment (cycle 1) was defined as DLT period. Pts manifesting an objective response or stable disease and likely to have clinical benefit from continued treatment were continued on GT0918 thereafter until they experienced one of following events of intolerable toxicities, disease progression or withdrew consent. Results: 18 pts were enrolled and treated with GT0918 since 9/6/2017 as defined in protocol at five dose levels: 100 mg (n = 3), 200 mg (n = 4), 300 mg (n = 4), 400 mg (n = 4) and 500 mg (n = 3) (as to 7/2/2019). All pts progressed more than two lines of therapies with 83.3% (15/18) pts were treated ≥3rd lines. Out of 6 confirmed AR positive pts, two (33.3%) at 300 mg cohort had finished 17 and 19 cycles individually and continue treatment (as 7/2/19). No DLT was observed and MTD has not been reached. GT0918 related adverse events (AEs) were grade 1 or 2 as per CTCAE v4.03, including fatigue, hypertriglyceridemia, anemia, hypercholesterolemia, increased LDL, nausea, loss of appetite, increased ALT, increase of weight loss, constipation and thrombocytopenia. PK profile analysis showed that in the single-dose study, GT0918 showed a fast absorption profile. In the multiple-dose study, the steady-state serum concentration level of GT0918 and its main metabolite were attained at 21 days. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated in late-stage pts. No DLT has occurred at maximum dose 500 mg. Pts with AR positive biomarker could have better clinical outcomes with GT0918 treatment. GT0918 and its main metabolite exhibited a nonlinear pharmacokinetic profile over the dose range from 100mg to 500 mg. An expanded/phase Ib in AR positive mBC pts has launched in China to evaluate the anti-tumor activity and safety of GT0918. 200 mg and 300 mg were selected for dose expansion. Citation Format: Huiping Li, Ran Ran, Guohong Song, Hanfang Jiang, Ruyan Zhang, Yaxin Liu, Luping Meng, Phoebe Zhang, Ke Chen, Qiaoxia Zhou, Karl Zhou, Youzhi Tong. Evaluation of safety, pharmacokinetics and pharmacodynamics of proxalutamide (GT0918), a potent androgen receptor (AR) blocker, in patients with metastatic breast cancer (mBC): Phase I dose escalation trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-17-05.

Background: Angiogenesis is a key mechanism of tumour growth. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2) and blocks downstream signalling and inhibiting tumour angiogenesis. It was approved in China to treat gastric cancer in October 2014. However, as breast cancer with a chest wall metastasis (CWM) has rich vascular distribution, whether Apatinib is also effective for breast cancer with a chest wall metastasis remains unknown. Therefore, we designed this clinical study to address this question. Method: The trial involved four centres in China from September 2016 to July 2019. It enrolled patients (pts) who were diagnosed of HER2 negative breast cancer with CWM and experienced first line or could not afford standard treatment. The patients were given Apatinib 500mg/day (single or combined with endocrine therapy if hormone receptor positive (HR+)) until progression or side effect not tolerated. Each patient had at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1.This study was approved by ethics committee at the Ethics Committee of Beijing Cancer Hospital, and all participants provided written informed consent. The trial was also Register to clinicaltrial.gov ( NCT02878057). Results: 30 pts were enrolled in the study with a median age of 50 (range 35-69) years old. Among the 30 pts, there were 23 ER positive pts (76.7%). 17 pts (56.7%) had more than 2 sites of metastasis, and 5 pts had invasive metastasis (16.6%). 15 pts (50%) were multi pre-treated. The response of 19 pts (63.3%) could be evaluated, and the overall response rate was 57.9% (no CR, 11 cases reached PR, 2 in HR-, 9 in HR+). and the median PFS was 8.6 months (range 0.5-29.5; 95% CI 0.0-18.7). The tumour in chest wall shrunk obviously. Side effects also existed. 15 pts (50%) had hypertension (grade 3: 6.7%); 10 pts (33.3%) had proteinuria (grade 3: 20%); 4 pts (13.3%) had fatigue (grade 3: 3.3%); 3 pts (10%) had bilirubin increase (grade 3: 6.7%). 8 pts discontinued the treatment due to side effects and 3 due to personal reasons. The Apatinib dose was reduced from 500mg to 250mg for most pts 18/30 (60%), and some pts took 500 mg and 250 mg every other day 10/30 (33.3). Conclusion: Apatinib was effective for pts with chest wall metastasis and pts could benefit from longer PFS. However, the side effects should be pay more attention from start on apatinib treatment. Citation Format: Huiping Li, Cuizhi Geng, Guohong Song, Hanfang Jiang, Zhongshen Tong, Junlan Yang, Ran Ran, Ruyan Zhang, Yaxin Liu, Xinyu Gui, Maorong Wei, Lu Xue. Apatinib in the treatment of HER-2 negative advanced breast cancer with chest wall metastasis multicenter phase II clinical study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-40.

Background: Fulvestrant 500mg has been proved better efficacy in breast cancer with hormone receptor positive (HR+),and then become an optional strategy for primary or second line treatment of HR+ positive metastasis breast cancer (MBC). Methods: In this real world study, we retrospectively analyzed the patients with HR+ HER 2 negative MBC who received fulvestrant 500mg treatment at Beijing cancer hospital during January 2015 to December 2018. Clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS) and adverse events were investigated. Results: There were 306 patients enrolled, median age was 48.7(range 20-75) years, median line of fulvestrant was 2.11(range 1-6), 68.3%(209/306) patients were involved with visceral metastasis. The CBR was 68.6%, median PFS was 8.41m (95%CI: 7.079m-9.743m, range 0.89m-80.16m). Among the patients received fulvestrant at the first line, the PFS was 10.55m(95%CI:6.46m-14.64m, range 0.92m-34.3m). The median OS hasn’t been obtained. In subgroup analysis, the patients without liver metastasis(12.49m vs. 4.60m, p4, 12.65m vs. 7.72m vs. 3.98m respectively, p2 lines, 14.06m vs. 7.79m vs. 3.52m respectively, p Conclusions: Fulvestrant was an effective and safe regimen in endocrine therapy for hormone receptor positive HER2 negative MBC. The patients who were in first line treatment, absence of liver metastasis and small tumor burden might be more benefit from fulvestrant. Corresponding authors: Huiping Li, huipingli2012@hotmail.com; Guohong Song, songguohong918@hotmail.com, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Rd, Beijing 100142, China Citation Format: Wen Lei, Huiping Li, Guohong Song, Ruyan Zhang, Ran Ran, Ying Yan. Efficacy observation of 306 patients with fulvestrant 500mg treatment in hormone-receptor positive HER2 negative metastasis breast cancer, a real world study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-20.

Background: Fulvestrant 500mg has proved its clinical effectiveness in previous trials as primary or second line treatment of hormone receptor positive, human epidermal receptor 2 negative (HR+/HER2˗) post-menopausal advanced breast cancer. This real-world study aimed to investigate the efficacy and safety of Fulvestrant in HR+/HER2˗ Chinese advanced breast cancer patients. Method: HR+/HER2˗ advanced breast cancer patients who received Fulvestrant 500mg from January 2015 to December 2018 in Beijing Cancer Hospital were enrolled in this retrospective study. Progression free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS) and adverse events (AEs) of Fulvestrant were investigated. Result: In total 303 enrolled patients [median age was 51 years (range: 21-82)], 255 (84.2%) patients were at postmenopausal status at the start of Fulvestrant treatment and 264 patients (87.1%) had advanced breast cancer. The median PFS (95% confidence interval) was 14.1 months (10.1-18.0) for the first-line, 11.2 months (2.2-20.3) for the second-line and 6.7 months (4.8-8.5) for ≥third-line of Fulvestrant. The ORR and CBR were 3.8% and 86.8% for the first-line, 5.5% and 75.4% for the second-line, 1.1% and 61.1% for ≥third-line of Fulvestrant. The multivariate subgroup analyses showed, PFS was significantly longer for the patients with light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free interval. For patients receiving Fulvestrant after palliative chemotherapy, the median PFS was numerically greater in maintenance treatment group than those who progressed after chemotherapy. Only 5.0% of patients (15/303) experienced adverse events and majority were grade 1-2. The most common adverse event was headache and palpitation, with merely one patient had severe adverse event (pulmonary embolism). Conclusion: Fulvestrant is an effective, safe and well-tolerated treatment regimen in endocrine therapy for HR+/HER2˗ metastatic breast cancer. Light tumor burden, less palliative chemotherapy before Fulvestrant and long disease-free survival (DFS) might be the ideal condition of Fulvestrant treatment. Fulvestrant can be effective for premenopausal patients with drug-induced menopause. Patients of different luminal subtypes can benefit from Fulvestrant. For patients with visceral metastases, presence of liver metastases rather than lung metastases was poor prognostic factor. Fulvestrant may also be considered as a maintenance treatment after first-line palliative chemotherapy.

Background. Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90–95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. Methods. Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. Results. Five patients (average age = 8.4 years; range = 5–10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. Conclusion. Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.

e13050 Background: This study was to compare the efficacy and safety of different nab-paclitaxel dose schedule in patients with HER-2 negative recurrent/metastatic breast cancer in order to find a more suitable treatment option for Chinese patients. Methods: This is a single-center, open-label, randomized, phase II trial. Eligible female patients with HER-2 negative recurrent/metastatic breast cancer and up to 2 lines of prior chemotherapy regardless of any endocrine therapy were randomly assigned (1:1) to either nab-paclitaxel (125mg/m2 IV days 1, 8, every 21 days, 3-week group) or nab-paclitaxel (125mg/m2 IV days 1, 8, 15, every 28 days, 4-week group) until progressive disease or completion of 6-8 cycles of treatment. After completing 6-8 cycles, if the efficacy evaluation is CR, PR or SD, the investigator can decide whether to carry out maintenance therapy. The primary endpoint is PFS. Secondary endpoints are ORR, OS and safety. Results: Between March 2019 and July 2021, 104 patients with HER-2 negative breast cancer were randomly assigned to treatment (3-week group, n = 51; 4-week group, n = 53). Median follow-up was 16.4 and 15.8 months. In the 3-week and 4-week groups, respectively, 39 (76.5%) and 42 (79.2%) patients had HR positive disease and 37 (72.5%) and 43 (81.1%) patients had visceral metastasis. In two groups, respectively, 30 (58.8%) and 20 (37.7%) patients didn’t receive prior endocrine therapy. 20 (39.2%) and 32 (60.4%) patients had received 1 to 3 lines of prior endocrine therapy. 30 (58.8%) patients of 3-week group and 30 (56.6%) patients of 4-week group were enrolled at first-line chemotherapy, and 13 (25.5%) of 3-week group patients and 16 (30.2%) patients of 4-week group were enrolled at second-line chemotherapy, as third-line chemotherapy there were only 8 (15.7%) in 3-week group and 7 (13.2%) in 4-week group. Among all patients, 33 (64.7%) in the 3-week group and 16 (30.2%) in the 4-week group had received 6-8 cycles according to the regimen of study, and 32 (97.0%) of 3-week group and 15 (93.8%) of 4-week group patients who finished the regimen choose to receive maintenance treatment (endocrine or chemotherapy).In two groups, respectively, median PFS was 9.6 months and 7.5 months (HR 0.905; 95%CI 0.569-1.440) and ORR were 50.0% (23/46) and 46.9% (23/49) in the evaluable population. Median OS was 22.5 months in the 3-week group and has not yet been reached for the 4-week group. According to NCI-CTCAE V5.0, 3-week group vs 4-week group respectively, the grade 3-4 adverse events (≥2 patients) were neutropenia (13.7% vs 34.0%), leukopenia (7.8% vs 17.0%) and peripheral neurotoxicity (0 vs 3.8%). Conclusions: Preliminary results suggest that compared with the 4-week regimen, the 3-week regimen of nab-paclitaxel seems to be more suitable and adaptable for Chinese patients with advanced breast cancer. This study is still in follow-up and updated data will be presented. Clinical trial information: NCT04192331.

The aim of the present study was to determine the efficacy and safety of lapatinib-based treatment for patients with human epidermal growth factor receptor-2-positive (HER2+) metastatic breast cancer (MBC). The aim of the present real-world study was to investigate the medical records and follow-up information of 92 patients with HER2+ MBC who received a lapatinib-based regimen at the recurrent/metastatic stage, 78 of whom had been pretreated with trastuzumab. The results demonstrated that the median progression-free survival (PFS) was 5.8 months and the overall survival (OS) was 21.5 months, with an objective response rate (ORR) of 21.7%, disease control rate (DCR) of 87.0% and clinical benefit rate (CBR) of 47.8%. In the patients receiving a lapatinib-based regimen as first-, second- and third/later-line treatment, the median PFS was 10.4, 5.2 and 5.1 months (P=0.048), the median OS was 32.9, 29.1 and 13.0 months (P

Background The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood. Methods A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test. Results Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048). Conclusions Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients., Highlights • High pCTL level predicts shorter first-line PFS in HER2+ patients receiving anti-HER2 based regimens. • The predictive role of pCTL level found in HER2+ patients was not applicable in HR+ and TNBC patients. • High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2+ breast cancer patients.

Background: More than 30% of estrogen receptor-positive breast cancers are resistant to primary hormone therapy, and about 40% that initially respond to hormone therapy eventually acquire resistance. Although the mechanisms of hormone therapy resistance remain unclear, aberrant DNA methylation has been implicated in oncogenesis and drug resistance. Purpose: We investigated the relationship between methylome variations in circulating tumor DNA and exemestane resistance, to track hormone therapy efficacy. Methods: We prospectively recruited 16 patients who were receiving first-line therapy in our center. All patients received exemestane-based hormone therapy after enrollment. We collected blood samples at baseline, first follow-up (after 2 therapeutic cycles) and at detection of disease progression. Disease that progressed within 6 months under exemestane treatment was considered exemestane resistance but was considered relatively exemestane-sensitive otherwise. We obtained circulating tumor DNA-derived methylomes using the whole-genome bisulfide sequencing method. Methylation calling was done by BISMARK software; differentially methylated regions for exemestane resistance were calculated afterward. Results: Median follow-up for the 16 patients was 19.0 months. We found 7 exemestane resistance-related differentially methylated regions, located in different chromosomes, with both significantly different methylation density and methylation ratio. Baseline methylation density and methylation ratio of chromosome 6 [32400000-32599999] were both high in exemestane resistance. High baseline methylation ratios of chromosome 3 [67800000-67999999] ( P = .013), chromosome 3 [140200000-140399999] ( P = .037), and chromosome 12 [101200000-101399999] ( P = .026) could also predict exemestane resistance. During exemestane treatment, synchronized changes in methylation density and methylation ratio in chromosome 6 [32400000-32599999] could accurately stratify patients in terms of progression-free survival ( P = .000033). Cutoff values of methylation density and methylation ratio for chromosome 6 [149600000-149799999] were 0.066 and 0.076, respectively. Conclusion: Methylation change in chromosome 6 [149600000-149799999] is an ideal predictor of exemestane resistance with great clinical potential.

BACKGROUD: Women with unilateral breast cancer are at increased risk for developing contralateral disease. The objective of the single-center retrospective study was to evaluate the incidence of bilateral breast cancer (BBC) and to analyze the clinicopathological characteristics for BBC in China. METHODS: We retrospectively reviewed the electronic medical records of 3924 female patients with breast cancer consecutively treated at the department of Breast Oncology in the Peking University Cancer Hospital between 2006 and 2016. BBC was categorized as synchronous (within 6 months) or metachronous bilateral breast cancer (after 6 months of a first tumor). Patients with BBC were identified according to the criteria described by Chaudary et al. Patients with stage IV first breast cancer, and those who were found to have distant metastases between the first and second primary breast cancer were excluded. Analyses of demographic, clinicopathologic, and treatment characteristics were done between sBBC and mBBC. RESULTS: The incidence of BBC in our population was 3.2% (127 of 3924). Of those, 2.5 % ( 99 of 3924) were metachronous bilateral breast cancer ( mBBC ), and 0.71 % (28 of 3924) were synchronous bilateral breast cancer ( sBBC ). The overall median age of the patients at first diagnosis was 45 years (range, 27-81 years). The age of onset of the first mBBC was significantly younger than that of sBBC ( p = 0.027). In mBBC subgroups, the median time interval between first and second tumors was 68 months (range, 7-342 months), and 80.8% of the second tumor were diagnosed within 10 years of the diagnosis of the first tumor. A positive family history of breast cancer was found in 25% of sBBC and 9.1% of mBBC ( p = 0.025). In ER-negative first tumor of mBBC, 56.1% of the second tumor were ER-positive. Mastectomy was the commonest surgery performed in these patients. CONCLUSIONS: Our results confirmed the necessity of screening contralateral breast at the diagnosis of unilateral breast cancer and following-up for Chinese patients with breast cancer. Citation Format: Li H, Jiang H, Zhang R, Shao B, Yan Y, Ran R, Di L. Bilateral breast cancer in China: A 10-year single-center retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-13.

Objective Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis. Circulating tumor cells (CTCs) are a promising predictor for breast cancer prognoses but their reliability regarding progression-free survival (PFS) is controversial. We aim to verify their predictive value in TNBC. Methods In present prospective cohort study, we used the Pep@MNPs method to enumerate CTCs in baseline blood samples from 75 patients with TNBC (taken at inclusion in this study) and analyzed correlations between CTC numbers and outcomes and other clinical parameters. Results Median PFS was 6.0 (range: 1.0-25.0) months for the entire cohort, in whom we found no correlations between baseline CTC status and initial tumor stage (P=0.167), tumor grade (P=0.783) or histological type (P=0.084). However, among those getting first-line treatment, baseline CTC status was positively correlated with ratio of peripheral natural killer (NK) cells (P=0.032), presence of lung metastasis (P=0.034) and number of visceral metastatic site (P=0.037). Baseline CTC status was predictive for PFS in first-line TNBC (P=0.033), but not for the cohort as a whole (P=0.118). This prognostic limitation of CTC could be ameliorated by combining CTC and NK cell enumeration (P=0.049). Conclusions Baseline CTC status was predictive of lung metastasis, peripheral NK cell ratio and PFS in TNBC patients undergoing first-line treatment. We have developed a combined CTC-NK enumeration strategy that allows us to predict PFS in TNBC without any preconditions.

Aim We aimed to clarify tumor features and prognosis of pregnancy‐associated breast cancer (PABC) among Chinese women. Methods PABC was defined as breast cancer diagnosed during pregnancy or within a year after delivery. Patients with PABC were selected from breast cancer cases of women ≤45 years treated at our institution between December 2012 and December 2017, and one non‐PABC control was matched for stage, age, and year of diagnosis for each case. Results Forty‐one women with PABC were identified (22 diagnosed during pregnancy and 19 within 1 year of delivery). There were significantly more progesterone receptor (PR)‐ and triple‐negative tumors in the PABC (56.1% and 24.4%, respectively) than in the non‐PABC group (31.7% and 4.9%, respectively) (P = .045 and .026, respectively). Human epidermal growth factor receptor 2 positivity was the same in both groups (31.7%). Median disease‐free survival (DFS) was 29.0 months (95% confidence interval [CI], 6.5‐51.5 months) in the PABC and 40.9 months (95% CI, 22.8‐58.8 months) in the non‐PABC group (P = .167). Median overall survival (OS) was 82.8 months in the PABC (95% CI, 39.3‐126.5 months) versus 80.1 months (95% CI, 56.7‐103.6 months) in the non‐PABC group (P = .131). Conclusion Histological features were similar in both groups, except that PR‐ and triple‐negative tumors were more frequent in the PABC group. Survival analyses show similar OS for patients with PABC and non‐PABC. DFS tended to be shorter in the PABC group; however, this difference was not statistically significant., After matching PABC cases with non‐PABC cases for stage and age (±1 year), as well as year of diagnosis secondarily (±1 year),on survival analysis, the median DFS tended to be shorter in women with PABC than in non‐PABC; however, this difference was not statistically significant and the median OS of the two groups were almost the same.

1019 Background: Androgen receptor (AR) is an emerging prognostic marker and therapeutic target in breast cancer. AR is expressed in 60% to 80% of breast cancers. Recent studies have shown the association between AR signaling and tumor carcinogenesis in breast cancer, suggesting AR pathway as a potential target for breast cancer treatment. However, no AR targeting therapies have been approved for treating breast cancer. GT0918 is a new chemical entity of AR antagonist with possible AR down-regulation. We had finished the phase I study and submitted the paper. Here we present a multicenter, open-label phase Ib trial assessing the safety and efficacy of GT0918 in women with AR positive metastatic breast cancer. The primary objective is to evaluate the efficacy of GT0918. The secondary objectives are to assess its safety and to explore the relevant biomarkers. Methods: This is an expansion study of a phase I dose-escalation trial. In this phase Ib study, only patients with AR positive metastatic breast cancer were enrolled. All eligibled patients would take GT0918 orally once a day, of a 28 -day cycle. After 2 cycles’ safety and tolerability assessment, patients could choose to continue their treatment until they experience disease progression, intolerable toxicities, death, or withdrew consent. The primary efficacy endpoints were 8-week disease control rate (DCR) and 16-week DCR. The secondary efficacy endpoint was progression free survival (PFS). Results: In total, 45 patients were enrolled in the study at 200mg (n = 30) and 300mg (n = 15) doses. The most common (≥10%) treatment-related adverse events (AEs) were asthenia (42.2%), aspartate aminotransferase increased (26.7%), blood cholesterol increased(17.8%), alanine aminotransferase increased (17.8%), decreased appetite (17.8%), blood triglycerides increased (13.3%), blood lactate dehydrogenase increased (13.3%), anaemia (13.3%), blood alkaline phosphatase increased (11.1%), gamma-glutamyltransferase increased (11.1%), urinary tract infection (11.1%). Grade 3/4 AEs were reported in 9 patients (20%). No treatment-related deaths occurred. The 8-week and 16-week DCR were both 22.2% (n = 10) (95% CI 10.08%, 34.37%). The median PFS was 1.8 months (95% CI 1.8, 1.9) in all patients. 12 out of 45 (26.7%) were triple negative breast cancer cases. The median PFS was 1.9 months (95% CI 1.7, 9.1), 4 out of 12 patients (33.3%) > 6 months, 2 out of 12 patients (16.7%) > 9 months. Conclusions: GT0918 has been shown to be well tolerated and may provide potential clinical benefits to AR positive metastatic breast cancer patients. This study demonstrated triple negative in AR positive patients had more benefit. Clinical trial information: NCT04103853 .

Background The impact of pregnancy on clinico-pathological features and prognosis of breast cancer remains controversial.We aimed to evaluate the impact of the association of pregnancy with breast cancer on tumor feature and prognosis- overall survival (OS) and disease free survival (DFS). Methods We defined Pregnancy Associated Breast Cancer (PABC) as breast cancer diagnosed during pregnancy or within a year following delivery. We enrolled PABC patients(pts) treated at our institution between December 2012 and December 2017 , and for each case, one non-PABC control was matched for stage, age, and year of diagnosis. Chis-quare and Fisher’s exact test, the Kaplan-Meier method, and Cox’s regression model were used. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Results 41 women with PABC were identified; 22 pts were diagnosed during pregnancy and 19 were diagnosed within one year of postpartum. There were more PR negative and triple negative tumors in the PABC(56.1% and 24.4%) than in the non-PABC(31.7% and 4.9%) (p = 0.045 and 0.026 respectively). The HER2 positivity was the same in the two group, both 31.7%. Median DFS in PABC pts was 29.0 months (95% CI range 6.5-51.5 months ) compared with 40.9 months (95% CI range 22.8–58.8 months) in the non-PABC pts(p = 0.167). Median OS in two groups were similar and even longer in PABC group, 82.8 months in PABC pts range(95% CI 39.3-126.5months) compared with 80.1 months (95% CI range 56.7-103.6months) in the non-PABC pts( p = 0.131). Conclusions The results show histological features were similar in both groups, except that triple-negative tumors were more common in the PABC group. The survival analyses show similar OS for patients diagnosed with PABC compared with non-PABC patients, and DFS tends to be shorter for PABC but no significant difference was observed. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e24029Background: In estrogen receptor-positive breast cancer patients (pts), more than 30% have primary hormone therapy (HT) resistance while the precise mechanism underlies remain unclear. Our st...