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BACKGROUND In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. PATIENTS AND METHODS Nine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and log rank test. RESULTS Four hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. CONCLUSION ER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Background: The 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative early breast cancer patients. The TAILORx showed that age would influence the interaction between RS and chemotherapy effect, and patients ≤50 years with RS >15 can benefit from chemotherapy. The current study aimed to determine the RS threshold that can predict chemotherapy benefit in both young and elder women. Methods: Patients diagnosed with pN0-1, ER+/HER2- breast cancer between 2009 and 2016 at Shanghai Ruijin hospital were retrospectively reviewed. A one-to-one propensity score matching (PSM) was performed between women receiving chemotherapy or not. Patients were then stratified by different cutoffs of age (range, 30-65 years). In each prespecified strata of age, cox proportional hazards models were used to determine the RS threshold which was predictive of chemotherapy benefit. Results: A total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS values that can manifest the chemotherapy benefit varied with age. For patients at 55 years of age or younger, apparent chemotherapy benefit was observed in those who had RS >25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) rate of 97.0% and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS rate: 95.3% vs. 94.6%). However, for patients older than 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS >36 (P = 0.014, 4-year IDFS rate: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS rate: 92.3% vs. 95.8%). Conclusions: The RS threshold to demonstrate the chemotherapy benefit differed with age. Young patients with RS >25 and old patients with RS >36 could benefit from adjuvant chemotherapy. Survival of breast cancer patients receiving adjuvant chemotherapy or not stratified by age and theChemoendocrine therapyEndocrine therapyP-value4-year IDFS rate (%)95% CI (%)4-year IDFS rate (%)95% CI (%)≤55 yearsRS ≤2595.390.7-100.094.689.6-100.00.66RS >2597.091.3-100.089.382.0-97.30.03>55 yearsRS ≤3692.387.7-97.295.892.1-99.60.13RS >3694.787.9-100.076.252.1-100.00.014 Citation Format: Jing Yu, Caijin Lin, Jiahui Huang, Jin Hong, Weiqi Gao, Siji Zhu, Hui Wang, Ou Huang, Xiaosong Chen, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Kunwei Shen, Jiayi Wu. Efficacy of adjuvant chemotherapy stratified by age and the 21 gene recurrence score in estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-28.

Background: It is unknown whether molecular subtype is associated with axillary lymph node (ALN) status (ypN) after neoadjuvant therapy (NAT) in breast cancer patients who achieved breast pathological complete remission (pCR), especially for patients with different clinical stage. Our study aimed to investigate the association of clinical stage and molecular subtype with ALN status (ypN) after NAT in breast cancer patients. Patients and methods: Breast cancer patients receiving ≥ 4 cycles of NAT with complete clinicopathological data were retrospectively included between January 2009 to January 2020. Status of ypN according to breast pCR status was compared in cT1-2N0, cT1-2N1, and local advanced breast cancer (LABC) patients with different molecular subtype. Univariate and multivariate analyses were conducted to identify potential predictive factors for ypN status. Results: A total of 1999 patients were included. cT1-2N0, cT1-2N1, and LABC disease were found in 457 (22.86%), 884 (44.22%) and 658 (32.92%) patients, whose ypN+ rate was 24.5%, 60.3%, and 66.4%, respectively (P < 0.001). Compared with cT1-2N0 patients, ypN+ rate was significantly higher in cT1-2N1 (OR = 5.48, 95%CI = 3.77-7.97, P < 0.001) and LABC (OR = 10.90, 95%CI = 7.12-16.70, P < 0.001). Moreover, ypN+ rate varied across different molecular subtypes, which was 60.0% in Luminal A subtype, 61.4% in Luminal B (HER2-) subtype, 47.6% in Luminal B (HER2+) subtype, 42.2% in HER2-amplified subtype and 52.5% in TNBC (P < 0.001). Patients achieving breast pCR also had a significantly lower ypN+ rate than those without breast pCR (23.9% vs 62.5%, univariate P < 0.001; OR =0.14, 95%CI = 0.09-0.21, P < 0.001). Furthermore, in breast pCR patients, multivariate analyses showed that clinical stage and molecular subtype were substantially related to ypN+ rate: the ypN+ rate was significantly higher in cT1-2N1 (OR = 5.64, 95%CI = 2.31-13.76, P < 0.001) and LABC (OR = 9.80, 95%CI = 3.88-24.77, P < 0.001), compared with cT1-2N0 patients; while it was significantly lower in Luminal B HER2+ (OR =0.20, 95%CI = 0.05-0.82, P = 0.025) and HER2-amplified (OR = 0.19, 95%CI = 0.05-0.83, P = 0.026) subtype, compared with Luminal A subtype. In the cT1-2N0 subgroup, all patients with breast pCR with Luminal B HER2+ or HER2-amplified subtype achieved ALN pCR. Conclusion: Clinical stage and molecular subtype were significantly associated with ypN status in breast pCR patients after NAT. Patients with cT1-2N0 and HER2-positive patients who achieved breast pCR had low ypN+ rate, which possibly guides further clinical ALN management after NAT. Key words: Breast pathological complete remission; Neoadjuvant therapy; Molecular subtype; Clinical stage; Nodal residual burden. Table. Pathological node status stratified by clinical stage between patients with breast pCR and non-pCR.Response in breastpCRnon-pCRypN0 (N, %)ypN+ (N, %)ypN0 (N, %)ypN+ (N, %)Whole population331(76.1)104(23.9)586(37.5)978(62.5)cT1-2N088(93.6)6(6.4)257(70.8)106(29.2)cT1-2N1159(74.3)55(25.7)192(28.7)478(71.3)LABC84(66.1)43(33.9)137(25.8)394(74.2)Luminal A like9(69.2)4(30.8)37(36.3)65(63.7)cT1-2N06(85.7)1(14.3)19(73.1)7(26.9)cT1-2N13(50.0)3(50.0)12(27.9)31(72.1)LABC0(0.0)0(0.0)6(18.2)27(81.8)Luminal B like (HER2-)112(70.4)47(29.6)220(31.4)480(68.6)cT1-2N033(89.2)4(10.8)85(59.0)59(41.0)cT1-2N159(71.1)24(28.9)75(23.8)240(76.2)LABC20(51.3)19(48.7)60(24.9)181(75.1)Luminal B like (HER2+)89(83.2)18(16.8)140(42.4)190(57.6)cT1-2N019(100.0)0(0.0)70(83.3)14(16.7)cT1-2N146(83.6)9(16.4)43(30.5)98(69.5)LABC24(72.7)9(27.3)27(25.7)78(74.3)HER2 amplified66(82.5)14(17.5)97(48.0)105(52.0)cT1-2N014(100.0)0(0.0)42(82.4)9(17.6)cT1-2N125(78.1)7(21.9)32(42.1)44(57.9)LABC27(79.4)7(20.6)23(30.7)52(69.3)TNBC55(72.4)21(27.6)92(40.0)138(60.0)cT1-2N016(94.1)1(5.9)41(70.7)17(29.3)cT1-2N126(68.4)12(31.6)30(31.6)65(68.4)LABC13(61.9)8(38.1)21(27.3)56(72.7)Abbreviations: LABC, locally advanced breast cancer; HER2, human epidermal growth factor receptor 2; TNBC, triple negative breast cancer; pCR, breast pathological complete response. Citation Format: Jin Hong, Yiwei Tong, Ou Huang, Jiayi Wu, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Xiaochun Fei, Xiaosong Chen, Kunwei Shen. Molecular subtype and clinical stage influenced axillary lymph node response in breast cancer patients with breast pathological complete remission after neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-33.

Background The 21-gene recurrence score (RS) testing can predict the prognosis for luminal breast cancer patients. Meanwhile, patients > 50 years with RS > 25 have improved survival with adjuvant chemotherapy. The current study aimed to develop a nomogram with routine parameters to predict RS. Methods We included patients diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative who underwent the 21-gene RS testing and aged > 50 years. The primary outcome was high-risk RS (> 25). Univariate and multivariate analyses were performed to identify significant predictors. A predictive nomogram based on logistic model was developed and evaluated with receiver operating characteristic (ROC) curves. The nomogram was internally validated for discrimination and calibration with bootstrapping method, and externally validated in another cohort. We then assessed the nomogram in different subgroups of patients and compared it with several published models. Results A total of 1100 patients were included. Five clinicopathological parameters were used as predictors of a high-risk RS, including tumor grade, histologic subtype, ER expression, PR expression, and Ki-67 index. The area under the curve (AUC) was 0.798 (95% CI 0.772–0.825) and optimism adjusted AUC was 0.794 (95% CI 0.781–0.822). External validation demonstrated an AUC value of 0.746 (95% CI 0.685–0.807), which had no significant difference with the training cohort (P = 0.124). Calibration plots indicated that the nomogram-predicted results were well fitted to the actual outcomes in both internal and external validation. The nomogram had better discriminate ability in patients who had tumors > 2 cm (AUC = 0.847, 95% CI 0.804–0.890). When compared with four other existing models, similar AUC was observed between our nomogram and the model constructed by discriminate Lee et al. Conclusions We developed a user-friendly nomogram to predict the high-risk RS in luminal breast cancer patients who were older than 50 years of age, which could guide treatment decision making for those who have no access to the 21-gene RS testing.

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Among 800 patients recruited between 2009 and 2016, the median RS was 24 (0-69), with 27.4%, 46.8%, and 25.9% patients classified into low-, intermediate-, and high-risk groups. Cox regression analysis demonstrated that the high-risk category was associated with significantly higher odds of invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) events compared with the low-risk category (IDFS: HR = 2.450, 95% CI 1.017-5.902, P = 0.046; DDFS: HR = 2.829, 95% CI 1.013-7.901, P = 0.047). No significant association between RS category and overall survival (OS) was found (intermediate vs. low: HR= 1.244, 95% CI 0.292-5.297, P = 0.768; high vs. low: HR = 2.933, 95% CI 0.759-11.327, P = 0.119). RS, as a continuous variable, was a highly significant predictor for IDFS (HR= 1.028, 95% CI 1.010-1.047, P = 0.002), DDFS (HR= 1.030, 95% CI 1.010-1.051, P = 0.003), and OS (HR= 1.034, 95% CI 1.007-1.063, P = 0.014). Our findings suggested that RS may predict IDFS in Chinese patients with ER+/HER2- breast cancer with N0 or N1 disease.

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab., Highlights • ER+/HER2+ early breast cancer patients treated with trastuzumab-based chemotherapy had superior prognosis. • ER+/HER2+ early breast cancer patients had distinct patterns of relapse or death from those of ER+/HER2-patients. • HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.

Background The interplay between biomarkers of insulin and the insulin-like growth factor (IGF) axis in the context of breast cancer risk is unclear. Methods We measured the concentrations of insulin, C-peptide, IGF1, and IGF binding protein 3 (IGFBP3) and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) index and the IGF1/IGFBP3 ratio among 2536 patients with breast cancer and 2528 patients with benign breast disease recruited from Ruijin Hospital, Shanghai, China, between 2012 and 2017. Results Multivariable-adjusted odds ratios (ORs) for breast cancer associated with the highest quartiles versus the lowest quartiles of insulin and IGF factors were 1.45 (95% CI, 1.20-1.75) for insulin, 1.32 (1.08-1.60) for C-peptide, 1.53 (1.26-1.85) for HOMA-IR, and 1.27 (1.05-1.53) for IGF1; these associations did not differ substantially across stratifications of age, body mass index, age at menarche, or menopausal status (all P for interaction >0.05). In the joint analysis, the highest quartile of IGF1 was associated with the greatest risk of breast cancer in the highest quartiles of insulin (OR, 1.77; 95% CI, 1.29-2.44), C-peptide (1.60; 1.17-2.20), and HOMA-IR (1.90; 1.38-2.62), compared with the risks associated with the combination of the lowest quartiles of IGF1 and each insulin factor. In stratification analysis, the positive association between IGF1 and breast cancer was stronger in the highest quartiles of insulin (P[interaction] = 0.29), C-peptide (P[interaction] = 0.020), and HOMA-IR (P[interaction] = 0.075). Conclusion Our findings indicate effect modifications of insulin, C-peptide, and insulin resistance on the relationship between IGF1 and breast cancer risk in Chinese women.

The recommendations for the diagnosis of stage 1 hypertension were recently revised by the American Heart Association primarily based on its impact on cardiovascular disease risks. Whether the newly diagnosed stage 1 hypertension impacts pregnancy complications remain poorly defined. We designed a retrospective cohort study to investigate the associations of stage 1 hypertension detected in early gestation (

Objectives: This study aims to evaluate influence factors for adjuvant chemotherapy regimen choice on the basis of trastuzumab in older human epidermal growth factor receptor 2 (HER2)-positive breast cancer under multi-disciplinary team (MDT) modality. Materials and Methods: HER2-positive breast cancer patients aged ≥ 60 years who received breast cancer surgery between April 2013 and December 2017 in Shanghai Ruijin Hospital were retrospectively enrolled. Clinical and pathological features, MDT recommendations, administration of adjuvant treatment, cardiotoxicity, and disease outcome information were reviewed and analyzed. Results: A total of 222 older HER2-positive breast cancer patients were included and recommended to receive adjuvant chemotherapy plus trastuzumab therapy. Paclitaxel plus trastuzumab (PH, 41/222, 18.5%), docetaxel plus carboplatin and trastuzumab (TCH, 62/222, 27.9%), and antharcyclines plus cyclophosphamide followed by taxanes and trastuzumab (AC-TH, 119/222, 53.6%) were the three main regimens. Patients with T1a-b (P

PurposeThis retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).Materials and MethodsPatients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.ResultsThe MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).ConclusionRS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Purpose: To evaluate the association of clinical early response and pathological complete remission (pCR) in breast cancer patients with different molecular subtypes. Materials and methods: Breast cancer patients who received neoadjuvant treatment (NAT) with clinical early response assessment from October 2008 to October 2018 were retrospectively analyzed. Clinical early response was defined as tumor size decreasing ≥30% evaluated by ultrasound after two cycles of NAT. Chi-square test was used to compare the pCR rates between the responder and non-responder groups with different molecular subtypes. Multivariate logistic regression was used to identify independent factors associated with the pCR. Results: A total of 328 patients were included: 100 responders and 228 non-responders. The progesterone receptor (PR) expression was an independent factor associated with clinical early response (OR=2.39, 95%CI=1.41-4.05, P=0.001). The pCR rate of breast was 50.0% for responders and 18.0% for non-responders (P

BackgroundThe 21-gene recurrence score (RS) can predict chemotherapy benefit in estrogen receptor-positive, human epidermal growth factor receptor-2-negative (ER+/HER2-) early breast cancer patients. Age would influence the interaction between RS and chemotherapy effect. The current study aimed to determine RS thresholds which were predictive of chemotherapy benefit in young and old women, respectively.MethodsPatients diagnosed with pN0–1, ER+/HER2- breast cancer between 2009 and 2016 were retrospectively reviewed. Propensity score matching was performed according to chemotherapy usage. After stratifying patients with different cutoffs of age, the RS threshold indicating chemotherapy benefit in each age strata were determined by cox proportional hazard models.ResultsA total of 1227 patients were included. The median age was 58 years and the median RS was 24. After matching, the RS thresholds suggesting chemotherapy benefit varied with age. For patients ≤55 years, chemotherapy benefit was observed in those having RS > 25 (P = 0.03), with 4-year invasive disease-free survival (IDFS) of 97.0 and 89.3% in patients receiving chemotherapy or not. While patients derived no benefit from chemotherapy if they had RS ≤25 (P = 0.66, 4-year IDFS: 95.3% vs. 94.6%). For patients > 55 years, adjuvant chemotherapy was associated with better prognosis in those with RS > 36 (P = 0.014, 4-year IDFS: 94.7% vs. 76.2%), but not in those having RS ≤36 (P = 0.13, 4-year IDFS: 92.3% vs. 95.8%).ConclusionsOld patients need higher RS thresholds to demonstrate the chemotherapy benefit. Further efforts are warranted to investigate the association between age and predictive RS thresholds.

Purpose The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes. Materials and Methods A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with ≥50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival. Results SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p

The 21-gene recurrence score (RS) assay is prognostic and predictive for hormone receptor (HR)+/HER2-/node- breast cancer (BC) patients. However, its clinical value in node + patients hasn’t been elucidated. HR+/HER2-/pN1 patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital from January 2014 to December 2018, with available RS results were retrospectively included. Clinico-pathological characteristics were compared. Adjuvant chemotherapy recommendations pre-/post- RS assay and actual usage were analyzed. A total of 303 patients were included, with 59, 178, 66 RS P P = 0.013), and RS category (P P P = 0.003) RS were more likely to be recommended with chemotherapy. RS independently influence chemotherapy decision in postmenopausal population as well. Chemotherapy recommendation changed for 9.57% patients after RS assay. Patient adherence rate to chemotherapy recommendation was 94.72% (287/303). The 21-gene RS independently influenced chemotherapy recommendation in pN1 BC patients, which could provide additional information to guide chemotherapy decision with relatively good treatment adherence rate.

Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes. Data from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated. IDC/DCIS patients were more likely to be younger (P

Yi-Wei Tong, Gen Wang, Jia-Yi Wu, Ou Huang, Jian-Rong He, Li Zhu, Wei-Guo Chen, Ya-Fen Li, Xiao-Song Chen, Kun-Wei ShenComprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaPurpose: HER2-positive breast cancer (BC) achieving pathological complete remission (pCR) after neoadjuvant therapy (NAT) had a superior disease outcome. Dysmetabolism and stimulation of insulin-like growth factor 1 (IGF-1)-axis would increase BC risk, but we are lacking data for their association with pCR in HER2-positive+ BC. We aim to evaluate the pCR predictive value of above factors in HER2-positive BC patients receiving NAT.Patients and methods: HER2-positive BC patients receiving NAT ± trastuzumab were retrospectively included between January 2013 and December 2016. Data were compared between baseline at biopsy and surgery. Median value of IGF-1 expression was used as cutoff value to classify patients into low or high group. pCR was defined as no residual invasive carcinoma in breast and axilla.Results: Overall, 101 patients were included. Metabolic syndrome was diagnosed in 29 (28.71%) with an average of 1.71±1.51 metabolic disorders at baseline, significantly increased after NAT (2.12±1.54, P

Background: Immune responses play an important role in the development of breast cancer. Trastuzumab can activate antibody-dependent cellular cytotoxicity (ADCC) in human epidermal growth factor receptor-2 (HER-2)-positive breast cancer. Many studies have demonstrated that inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC), are associated with prognosis in breast cancer. The aim of this study was to explore whether preoperative NLR, ALC or the absolute neutrophil count (ANC) is associated with prognosis in HER-2-positive breast cancer patients who received adjuvant trastuzumab. Patients and methods: Three hundred sixty-seven female patients with HER-2-positive invasive breast cancer who were treated with one-year adjuvant trastuzumab were analysed in this retrospective study. Preoperative haematological parameters, clinicopathological data and survival data were obtained. The cut-off points for ALC, ANC and NLR were based on the median values. Disease-free survival (DFS) and Overall survival (OS) were analysed by the Kaplan-Meier method. Multivariable Cox regression was used to determine the independent prognostic significance of ALC, ANC and NLR. Results: Survival analysis revealed that the 3-year DFS in patients with high ALC was 89.0%, which was significantly worse than 95.0% in patients with low ALC (p=0.014). Kaplan-Meier analysis also showed that patients with low NLR had a poorer 3-year DFS than patients with high NLR (89.7% vs 94.0%, respectively; p=0.047). Multivariate analysis showed that ALC was an independent prognostic factor for DFS (HR=2.723; 95% CI=1.211-6.122; p=0.015). Neither ANC, ALC nor NLR could predict OS independently. Conclusion: In HER-2-positive breast cancer patients who were treated with adjuvant trastuzumab, a high ALC is significantly associated with a poor DFS.

Background Breast cancer patients with suspicious axillary lymph node (ALN) at ultrasound and positive fine-needle aspiration (FNA) results were required to receive ALN dissection (ALND), which was not certain in the post-ACOSOG Z0011 era. We aim to evaluate the ALN metastasis burden in these patients, thus to illustrate whether they can follow the ACOSOG Z0011 trial procedure. Methods Clinically, T1–2 N0 breast cancer patients with positive preoperative ALN biopsy (FNA group) or 1–2 positive sentinel nodes (SLNB group) were retrospectively analyzed. ALN metastasis burden was compared between the two groups, which were further analyzed in certain subtypes. An association between clinicopathological factors and ≥ 3 ALN metastasis was also analyzed. Results A total of 388 patients were included: 202 in the FNA group and 186 in the SLNB group. The FNA group had a significantly higher number of positive ALN (5.18 vs. 1.77, P

PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (PER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all PP=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

Background Trastuzumab has changed the prognosis of HER2+ breast cancer. We aimed to investigate the prognosis of ER+/HER2+ patients treated with trastuzumab, thus to guide escalation endocrine treatment in ER+ breast cancer. Methods ER-positive early breast cancer patients operated at Ruijin Hospital between Jan. 2009 and Dec. 2017 were retrospectively included. Eligible patients were grouped as HER2-negative (HER2-neg) or HER2-positive with trastuzumab treatment (HER2-pos-T). Kaplan-Meier analysis and Cox proportional hazards model were used to compare the disease-free survival (DFS) and overall survival (OS) between these two groups. Results A total of 3761 patients were enrolled: 3313 in the HER2-neg group and 448 in the HER2-pos-T group. Patients in the HER2-pos-T group were associated with pre/peri-menopause, higher histological grade, LVI, higher Ki-67 level, lower ER and PR levels (all P P = 0.185), respectively. Multivariable analysis demonstrated that patients in the HER2-pos-T group had a better DFS than patients in the HER2-neg group (HR 0.52, 95% CI: 0.37–0.73, P P = 0.133). Multivariate analysis found that HER2-pos-T group was still associated with significantly better OS compared with the HER2-neg group (HR 0.38, 95% CI: 0.22–0.67, P = 0.037). Conclusion ER+/HER2+ breast cancer patients treated with trastuzumab were associated with superior outcome compared with ER+/HER2- patients, indicating HER2-positivity itself may not be an adverse factor for ER+ patients in the era of trastuzumab.

Background: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear.Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment.Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29–0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27–1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18–0.89), were premenopausal (HR, 0.34; 95% CI, 0.12–0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17–0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25–0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26–0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence.Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors.

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown.Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups.Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS

Background Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer. Methods This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life. Results There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group (p = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening (p = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group (p = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups. Conclusions TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients. Trial registration ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered).

Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ≤1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging.Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18–30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated.Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%.Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients.

Purpose: Dysmetabolism and high circulating insulin-like growth factor 1 (IGF-1) would increase breast cancer risk, but its association with survival in HER2+ breast cancer patients has not been well-studied. Herein, we aim to evaluate the prognostic value of IGF-1 and metabolic abnormalities in HER2+ population.Patients and Methods: HER2+ breast cancer patients treated in Ruijin Hospital between November 2012 and June 2017 were retrospectively analyzed. Median value of circulating IGF-1 was adopted to classify low or high IGF-1 group. Metabolic syndrome (MetS) was defined using AHA/NHLBI criteria. Overweight was defined by body mass index (BMI) ≥ 24.0 kg/m2 in Chinese population.Results: Overall, 679 patients were included and 209 had synchronous MetS. High IGF-1 level was more common in pre/peri-menopausal women (P < 0.001) and high IGFBP-3 patients (P < 0.001). After a median follow-up of 36 months, 52 patients had disease recurrences. IGF-1 level was not associated with recurrence-free survival (RFS, P = 0.620) in the whole population. However, exploratory subgroup analysis found that BMI and IGF-1 interacted in predicting RFS (P = 0.009). For non-overweight patients, high IGF-1 showed a superior 4-years RFS (91.1 vs. 85.0%; HR 0.53, 95% CI 0.27–1.00, P = 0.049) compared with patients with low IGF-1 level. In contrast, for overweight patients, high IGF-1 was associated with an impaired 4-years RFS (88.3 vs. 95.7%, HR 3.20, 95% CI 1.00–10.21, P = 0.038). Furthermore, high IGF-1 level was independently associated with better OS in the whole (HR 0.26, 95% CI 0.08–0.82, P = 0.044) as well as non-overweight population (HR 0.15, 95% CI 0.03–0.68, P = 0.005).Conclusions: IGF-1 level was not associated with RFS in HER2+ breast cancer patients. However, IGF-1 and BMI had significant interaction in disease outcome prediction in HER2+ patients. High IGF-1 was protective in non-overweight patients, but risk factor for those overweight, which deserves further evaluation.

Background: Despite low aggressiveness in tumor biology and high responsiveness to endocrine therapy, subgroups of patients with estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer relapse early in the first two years after initiation of endocrine therapy, indicating potential endocrine resistance. Accordingly, we attempted to establish a scoring system to inform the first-2-year prognosis (F2P Score). Methods: Patients with node-negative ER+/HER2- breast cancer and complete data of gene expressions in a 21-gene panel were retrospectively retrieved from Shanghai Jiao Tong University Breast Cancer Database (SJTU-BCDB). The F2P Score was established based on the clinical and genomic variables associated with the first-2-year relapse after shrinkage correction and validated using the bootstrap resampling method. Model performance was quantified by Harrell's concordance-index (C-index) and Bayesian information criteria (BIC). Results: The F2P Score was established by integrating the clinical (age and tumor size) and genomic (ESR1, PGR, BCL2, CD68, GSTM1, and BAG1) variables with a C-index of 0.71 and BIC of 397.46. Bootstrap C-index was 0.72 (95% CI, 0.62-0.81) and BIC was 396.75 (95% CI, 252.37-541.13). A higher score indicated an increased likelihood of a first-2-year relapse, when used as continuous (HR, 2.94; 95% CI, 1.87-4.61) or categorical (HR, 3.68; 95% CI, 1.70-8.00) predictors in multivariate analysis. Both continuous and categorical F2P Score also remained prognostic for overall survival and other endpoints. No significant interaction was observed between the F2P Score and treatment subgroups. Additionally, the F2P Score outperformed the IHC4, clinical treatment score and 21-gene test in predicting first-2-year relapse. Conclusion: The F2P Score reported herein, integrating the clinicopathological and genomic variables, may inform prognosis and endocrine responsiveness. After the benefits and risks have been considered, treatment escalation may be an alternative strategy for patients with a higher score.

OBJECTIVES To determine whether imaging and clinicopathologic features could predict false-positive axillary ultrasound (US) results in the selection of patients with breast cancer who had a heavy axillary tumor burden (≥3 tumor-involved nodes). METHODS Among 788 patients with histologically confirmed invasive breast cancer at Ruijin Hospital from October 2014 to September 2015, 162 patients (cT1-T2, cN0) with 167 axillae had suspicious axillary US findings. Ultrasound findings were considered suspicious for metastasis if cortical thickening of greater than 3 mm or effacement of the fatty hilum was present. The false-positive rate of suspicious axillary US results for identifying 3 or more positive lymph nodes in the final pathologic examination was calculated. Univariate and multivariate analyses were used to evaluate imaging and clinicopathologic factors related to the false-positive results. RESULTS Axillary US showed a false-positive rate of 60.5% (101 of 167) in the patients with breast cancer and a heavy nodal burden. By logistic regression analyses, we found false-positive axillary US results more frequently in patients who had a T1 stage tumor (P = .005), an estrogen receptor/progesterone receptor-negative tumor (P

The 21-gene recurrence score (RS) is increasingly being used for patients with early stage, hormone receptor-positive, Her-2-negative breast cancer. However, these results are largely from populations with infiltrating ductal carcinoma (IDC). The clinical value of RS testing in mucinous carcinoma has not been well investigated. Pure mucinous breast cancer (PMBC) and paired pure IDC patients who underwent 21-gene RS were retrospectively reviewed and matched with tumor stage and molecular subtype. Clinic-pathological factors, treatment strategies, and RS distribution were compared between the PMBC and IDC patients. A total of 35 PMBC and 70 IDC patients were included. We found that RS was lower in the PMBC as compared with the IDC group: 21.26 vs. 24.40 (P=0.037). Regarding RS categories, PMBC patients had a relatively lower percentage of high RS patients than the IDC group: 8.57% vs. 22.86% (P = 0.048). Multivariate analysis showed that histologic type was an independent factor predicting RS distribution: IDC patients were associated with a higher RS as compared with PMBC patients (OR: 1.27, 95% CI: 1.03-2.13; P=0.014). Among genes in 21-gene RS testing, HER2, STMY3, STK15, and BAG1 were significantly different between the PMBC and IDC groups (P < 0.05). Two patients (5.71%) in the PMBC group, both with high RS, were recommended to receive adjuvant chemotherapy, much lower than patients with IDC (57.14%, P < 0.001). In multivariate analysis, histologic type of IDC was an independent factor for chemotherapy recommendation (OR = 22.00, 95% CI: 4.89-98.97, P

Background: Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia (VAP) in trauma patients. Methods: This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy (de-escalation group) or non-de-escalation therapy (non-de-escalation group). Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. Results: Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups (28.6% vs. 23.8%, P = 0.620). The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group(11 [8–13] vs. 14 [8–19] days, P = 0.045). The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group (6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively). Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, high injury severity score, multi-drug resistant (MDR) infection, and inappropriate initial antibiotics were associated with patients’ 28-day mortality, while high APACHE II score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. Conclusions: De-escalation strategy in the treatment of trauma patients with VAP could reduce the duration of antibiotics treatments and expense of hospitalization, without increasing the 28-day mortality and MDR infection. Key words: De-Escalation; Propensity Score Matching; Trauma; Ventilator-Associated Pneumonia

Background Multidisciplinary treatment (MDT) and adjuvant therapy are associated with improved survival rates in breast cancer. However, nonadherence to MDT decisions is common in patients. We developed a smartphone-based app that can facilitate the full-course management of patients after surgery. Objective This study aims to investigate the influence factors of treatment nonadherence and to determine whether this smartphone-based app can improve the compliance rate with MDTs. Methods Patients who had received a diagnosis of invasive breast cancer and had undergone MDT between March 2013 and May 2019 were included. Patients were classified into 3 groups: Pre-App cohort (November 2017, before the launch of the app); App nonused, cohort (after November 2017 but not using the app); and App used cohort (after November 2017 and using the app). Univariate and multivariate analyses were performed to identify the factors related to MDT adherence. Compliance with specific adjuvant treatments, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapy, was also evaluated. Results A total of 4475 patients were included, with Pre-App, App nonused, and App used cohorts comprising 2966 (66.28%), 861 (19.24%), and 648 (14.48%) patients, respectively. Overall, 15.53% (695/4475) patients did not receive MDT recommendations; the noncompliance rate ranged from 27.4% (75/273) in 2013 to 8.8% (44/500) in 2019. Multivariate analysis demonstrated that app use was independently associated with adherence to adjuvant treatment. Compared with the patients in the Pre-App cohort, patients in the App used cohort were less likely to deviate from MDT recommendations (odds ratio [OR] 0.61, 95% CI 0.43-0.87; P=.007); no significant difference was found in the App nonused cohort (P=.77). Moreover, app use decreased the noncompliance rate for adjuvant chemotherapy (OR 0.41, 95% CI 0.27-0.65; P Conclusions This smartphone-based app can increase MDT adherence in patients undergoing adjuvant therapy; this was more obvious for adjuvant chemotherapy and radiotherapy.

Background: Composite measure of recurrence risk with certain clinicopathologic characteristics provided prognostic and adjuvant ovarian function suppression (OFS) therapeutic effect information for patients in the TEXT and SOFT trials, but the role of this composite risk score (CRS) in OFS treatment decision-making has not been established. We carry out this study to evaluate the association of CRS with OFS treatment recommendation in our multidisciplinary team (MDT) treated patient cohort.Methods: Premenopausal patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer who received surgery between April 2013 and December 2018 and had OFS decision-making made by MDT were included. The association of CRS with OFS recommendation and survival outcome were analyzed.Results: Totally 887 patients were identified, amongst which 239 (26.94%) were recommended to receive OFS. The median CRS was 1.92, 455 (51.3%) patients were categorized as low-risk and 432 (48.7%) as high-risk. Age < 35 years (OR = 24.68, 95% CI 12.97-46.95, P < 0.001), ≥ 4 ALNs metastasis (OR = 3.95, 95% CI 2.08-7.48, P < 0.001), ER ≥ 50% (OR = 5.45, 95% CI 2.16-13.75, P < 0.001) and CRS high-risk (OR = 2.82, 95% CI 1.62-4.91, P < 0.001) were independently predictive of OFS recommendation. CRS also served as an effective predictor of OFS recommendation in receiver operating characteristics (ROC) curve analysis (AUC = 0.775, P < 0.001). CRS high-risk was related to worse breast cancer-free interval (BCFI) (89% vs. 97.6%, HR 8.98, 95% CI 2.73-29.51, P < 0.001), no significant differences in overall survival (OS) were found between patients with CRS high and low-risk (96.5% vs. 99.8%, HR 5.5, 95% CI 0.66-45.73, P = 0.076).Conclusions: CRS was associated with OFS recommendation and BCFI in premenopausal patients with HR positive/HER2 negative breast cancer, which may be integral to their individualized OFS treatment decision-making. Table 1. Clinicopathologic characteristics, CRS and OFS recommendationUnivariate analysisMultivariate analysischaracteristicsNo-OFS N = (%)OFS N = (%)P valueOR95% CIP valueAge (years)< 0.001< 0.001< 3521 (23.33)69 (76.67)24.6812.97-46.95< 0.00135-3940 (30.77)90 (69.23)22.8713.59-38.48< 0.001≥ 40587 (88.01)80 (11.99)1Histologic grade< 0.0010.054I84 (94.38)5 (5.62)1II409 (73.96)144 (26.04)3.691.28-10.650.016III155 (63.27)90 (36.73)3.481.11-10.860.032Tumor size0.0120.172≤ 2cm428 (75.89)136 (24.11)1> 2cm220 (68.11)103 (31.89)0.720.45-1.15ALN status< 0.001< 0.0010421 (80.04)105 (19.96)11-3171 (68.95)77 (31.05)1.91.14-3.170.014≥ 456 (49.56)57 (50.44)3.952.08-7.48< 0.001ER0.022< 0.001< 50%53 (85.48)9 (14.52)1> 50%595 (72.12)230 (27.88)5.452.16-13.75PR0.052< 50%202 (68.94)91 (31.06)≥ 50%446 (75.08)148 (24.92)Ki67< 0.0010.466< 14%270 (84.38)50 (15.63)114%-19%48 (70.59)20 (29.41)1.650.77-3.530.20220%-25%127 (73.84)45 (26.16)1.110.6-2.060.747≥ 26%203 (62.08)124 (37.92)1.430.8-2.560.231CRS< 0.001< 0.001≤ 1.92405 (89.01)50 (10.99)1> 1.92243 (56.25)189 (43.75)2.821.62-4.91 Table 2. ROC analysis for prediction of OFS recommendationcharacteristicsAUCP valueAge (years)0.109 Citation Format: Yue Liang, Xiaosong Chen, Weiqi Gao, Siji Zhu, Jin Hong, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Yafen Li, Weiguo Chen, Kunwei Shen. Can composite risk model help clinicians make adjuvant ovary function suppression dicision for breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-10.

// Jiayi Wu 1 , Yan Fang 1 , Lin Lin 2 , Xiaochun Fei 3 , Weiqi Gao 1 , Siji Zhu 1 , Yu Zong 1 , Xiaosong Chen 1 , Ou Huang 1 , Jian-Rong He 1 , Li Zhu 1 , Weiguo Chen 1 , Yafen Li 1 and Kunwei Shen 1 1 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China 2 Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China 3 Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China Correspondence to: Kunwei Shen, email: kwshen@medmail.com.cn Keywords: breast carcinoma, 21-gene, risk score, clinico-pathologic factors Received: August 31, 2016 Accepted: January 16, 2017 Published: March 17, 2017 ABSTRACT Aim: The current study aimed to explore the distribution patterns of 21-gene recurrence score (RS) assay in Chinese early breast cancer patients. Methods: Nine hundred and eighty consecutive estrogen receptor(ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients treated at Ruijin Hospital, Shanghai Jiaotong University, School of Medicine from 2009 to 2016 were retrospectively recruited. Reverse transcriptase-polymerase chain reaction (RT-PCR) assay of 21 genes were conducted in paraffin-embedded tumor tissue to calculate the RS. Co-relations of RS and clinico-pathologic factors were evaluated. Concordances of RT-PCR and immunohistochemistry (IHC) tests were measured. Logistic regression were applied to determine independent variables associated with RS. Results: The median RS of 980 patients was 23(0~90), and the proportions of patients categorized as having a low, intermediate, or high risk were 26.1%, 49.3% and 24.6%. The distribution of RS varied significantly according to different tumor grade, T stage, progesterone receptor(PR) status, Ki67 index and molecular subtypes (p

Few data exist to elucidate whether patients with a suspicious axillary lymph node (ALN) at ultrasound but a negative fine-needle aspiration result (FNA group) can be managed as having ultrasound node-negative disease (AUN group). This study compared various ALN statuses between the AUN and FNA groups to guide further ALN management.Patients who had clinical T1-2N0 breast cancer treated with sentinel lymph node (SLN) biopsy were retrospectively analyzed. The ALN metastasis status, SLN status, and non-SLN metastasis rates in the entire population and the patients with one or two positive SLNs were compared between the AUN and FNA groups.A total of 1007 patients (886 AUN and 121 FNA patients) were eligible for the final analysis: The incidence of ALN metastasis did not differ between the AUN group (16.5%) and the FNA group (21.5%) (P = 0.170). In addition, three or more metastases were found in only 2.4% of the AUN patients and 3.3% of the FNA patients (P = 0.405). The non-SLN metastasis rate was 22.6% (33/146) in the AUN group and 19.2% (5/26) in the FNA group (P = 0.699). For the patients with one or two positive SLNs, the rate of non-SLN metastasis was similar between the AUN group (19.6%, 27/138) and the FNA group (12.5%, 3/24) (P = 0.591).Patients with a suspicious ALN at ultrasound but a negative FNA result had ALN statuses similar to those of the ultrasound node-negative patients, indicating that these patients can be treated as having ultrasound node-negative disease.

Recurrence score (RS) could be used to predict clinical outcomes and chemotherapy efficacy in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. However, the clinical features and management of patients with an RS of 26-30 are not completely understood. In the present study, 783 patients with HR+/HER2-, lymph node-negative early breast cancer and RS ≥18 were included and categorized into RS=18-25 (47.8%), 26-30 (25.5%) or ≥31 (26.7%) groups. Clinicopathological characteristics, adjuvant chemotherapy usage and disease outcomes were compared. Alterations in the adjuvant chemotherapy recommendation after 21-gene RS testing were also analyzed. The results indicated that patients with RS=26-30 had higher progesterone receptor (PR) expression [odds ratio (OR)=2.84; P

Anthracycline chemotherapy serves an important role in treating patients with breast cancer but is associated with cardiotoxicity. Although brain natriuretic peptide (BNP) is not the ideal marker for detecting the presence of diseases of the heart, several studies have demonstrated the predictive utility of BNP in the diagnosis of anthracycline-induced cardiotoxicity (AIC). The aim of the present study was to evaluate the role of BNP as a marker for the early prediction of AIC in patients with breast cancer. In the present study, a total of 149 patients with breast cancer who received anthracycline therapy were evaluated. The levels of BNP and echocardiography were detected during the anthracycline-based chemotherapy and patients were followed up after chemotherapy to determine the cardiotoxicity-free survival times. In the patients who received chemotherapy, an increase in the levels of BNP was observed. The concentration of BNP was significantly higher in the cardiotoxicity group during anthracycline chemotherapy (P=0.022) compared with the non-cardiotoxicity group and it was an independent predictor of cardiotoxicity (P=0.028). The optimal diagnostic threshold of BNP after the last anthracycline chemotherapy treatment was 107.9 pg/ml, the diagnostic sensitivity was 0.538, the specificity was 0.794, the Youden index was 0.332, the positive predictive value was 0.583 and the negative predictive value was 0.762. Based on the BNP threshold, a log-rank test was performed and it was determined that the cardiotoxicity-free survival rate of the group with higher levels of BNP was always lower compared with the group with lower levels of BNP. BNP elevation was associated with cardiotoxicity during the anthracycline chemotherapy. Detecting BNP after the final treatment of anthracycline chemotherapy may contribute to the early detection of cardiotoxicity.

Luminal subtypes and the 21-gene recurrence score (RS) are important factors in the decision-making process for adjuvant chemotherapy in patients with hormonal receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, their effect on adjuvant chemotherapy decisions in the real world has not been thoroughly investigated, particularly for patients of the luminal A-like subtype with a high RS or the luminal B-like subtype with a low RS. The present study, a total of 772 HR(+)/HER2(−) patients who underwent 21-gene testing, were included in a retrospective analysis. The impact of clinicopathological factors and the 21-gene RS on chemotherapy recommendation was analyzed in the whole population and for patients of different luminal subgroups. The results revealed that chemotherapy was highly recommended for patients of younger age, with larger tumor size, node involvement, higher grade, luminal B-like subtype and higher RS. A high RS was identified to be the most important impact factor for chemotherapy recommendation among all patients [odds ratio (OR), 62.54; 95% CI, 25.58–152.92], the luminal A-like group (OR, 435.05; 95% CI, 29.90–6331.06) and the luminal B-like group (OR, 57.20; 95% CI, 22.42–145.96). For patients of the luminal A-like subtype with a high RS or patients of the luminal B-like subtype with low RS, the 21-gene RS was demonstrated to be the most important independent factor for chemotherapy recommendation, with an adjusted OR of 134.52 (95% CI, 10.39–1741.89). In conclusion, luminal subtypes and the 21-gene RS were found to be associated with chemotherapy recommendation for HR(+)/HER2(−) patients. For patients with a discordant luminal subtype and 21-gene RS risk, the 21-gene RS score was found to be the most important factor that influences chemotherapy decision, which warrants further clinical evaluation.

The roles of Ephrin B (EphB) receptors in cancer are relatively unknown as these receptors are associated with complex signaling pathways. A limited number of studies have investigated the association between EphB receptors and prognosis. Using the Kaplan-Meier plotter database, the present study investigated the associations between the mRNA expression levels of five EphB receptors and the outcomes of 3,554 patients with breast cancer who had been followed-up for 20 years. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated to assess the relative risk of survival. The results demonstrated that high mRNA expression levels of EphB2 (HR, 0.74; 95% CI, 0.66–0.84; P=2.1×10-6), EphB4 (HR, 0.82; 95% CI, 0.72–0.93; P=0.0023) and EphB6 (HR, 0.69; 95% CI, 0.61–0.78; P=3×10-9) were significantly associated with improved survival, while a high mRNA expression level of EphB3 (HR, 1.14; 95% CI, 1.01–1.28; P=0.029) was associated with worse survival for patients with breast cancer. High expression levels of all EphB receptors, including EphB1 (HR, 1.4; 95% CI, 1.02–1.94; P=0.039), EphB2 (HR, 1.34; 95% CI, 1.07–1.67; P=0.011), EphB3 (HR, 1.39; 95% CI, 1.11–1.73, P=0.0038), EphB4 (HR, 1.33; 95% CI, 1.06–1.67; P=0.013) and EphB6 (HR, 1.32; 95% CI, 1.05–1.65; P=0.016), were associated with an increased risk of mortality in patients with lymph-node-positive breast cancer. High mRNA expression levels of EphB1 were not associated with survival for all patients with breast cancer (HR, 0.85; 95% CI, 0.72–1.01; P=0.058). The results of the present suggested that EphB receptors may be useful as prognostic biomarkers of breast cancer.

Background There are limited data about how to manage patients with discordant hormonal receptor (HR) status between core needle biopsy (CNB) and following surgical sample (FSS). This study aimed to evaluate clinicopathological features and disease outcome for these HR discordance patients. Patients and Methods Invasive breast cancer patients with paired HR between CNB and FSS were retrospectively analyzed, being classified into three groups: HR positive, HR negative, and HR discordance. Patient characteristics, treatment decisions, and disease outcome were compared among above groups. Results A total of 1710 patients (1233 HR positive, 417 HR negative, and 60 HR discordance patients) were enrolled. Compared with the HR positive group, HR discordance patients were associated with more human epidermal growth factor receptor 2 positivity (P

Background: The prognosis of nasal type advanced-stage or relapsed extranodal NK/T cell lymphoma (ENKTL) is poor even with intensive multi-agent chemotherapy. It is therefore critical to develop more effective treatment strategies to improve outcomes and prognosis of ENKTL patients. Methods: We conducted a multi-center, prospective study to evaluate the efficacy and safety of a new treatment strategy: induction chemotherapy with gemcitabine, L-asparaginase or PEG-asparaginase, ifosfamide, dexamethasone and etoposide (GLIDE) followed by upfront autologous hematopoietic stem cell transplantation (ASCT) conditioning with either carmustine, etoposide, cytarabine, and melphalan (BEAM) or chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Findings: A total of 64 eligible patients were enrolled. After a maximum of 6 cycles of GLIDE, 43 patients (70·5%) achieved complete response, including 31 (50·8%) who achieved complete response after 2 cycles. With median follow-up of 23.8 months, estimated 5-year progression-free survival and overall survival of the whole cohort was 54·0% and 68.9% respectively. Among 50 chemo-sensitive patients (patients in complete or partial remission) , 27 underwent upfront ASCT, and they showed a significantly higher rate of 5-year progression-free survival than chemosensitive patients who did not receive upfront ASCT (78·8% vs. 36·0%, p=0·0004) as well as a significantly higher rate of 5-year overall survival (87·2% vs. 55·4%, p=0·0035). Interpretation: GLIDE chemotherapy showed a high efficacy in disease control for the patients with advance-staged or relapsed ENTKL, and in whom achieved partial or complete response, GLIDE followed by upfront ASCT may be a more effective treatment strategy than GLIDE alone. Trial Registration Information: The study was registered at the Chinese Clinical Trial Registry (Chictr.org.cn, Chicrt-TNC-10000782). Funding Statement: This work was supported by a grant from Science and Technology Fund of Sichuan Province, China, NO.18ZDYF2063. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital, Sichuan University. Written informed consent was obtained from all patients.

Background: Sepsis is a dysregulated host response to pathogens. Delay in sepsis diagnosis has become a primary cause of patient death. This study determines some factors to prevent septic shock in its early stage, contributing to the early treatment of sepsis. Methods: The sequencing data (RNA- and miRNA-sequencing) of patients with septic shock were obtained from the NCBI GEO database. After re-annotation, we obtained lncRNAs, miRNA, and mRNA information. Then, we evaluated the immune characteristics of the sample based on the ssGSEA algorithm. We used the WGCNA algorithm to obtain genes significantly related to immunity and screen for important related factors by constructing a ceRNA regulatory network. Result: After re-annotation, we obtained 1708 lncRNAs, 129 miRNAs, and 17 326 mRNAs. Also, through the ssGSEA algorithm, we obtained 5 important immune cells. Finally, we constructed a ceRNA regulation network associated with SS pathways. Conclusion: We identified 5 immune cells with significant changes in the early stage of septic shock. We also constructed a ceRNA network, which will help us explore the pathogenesis of septic shock.

// Yan Fang 1, * , Jiayi Wu 1, * , Wei Wang 1 , Xiaochun Fei 2 , Yu Zong 1 , Xiaosong Chen 1 , Ou Huang 1 , Jianrong He 1 , Weiguo Chen 1 , Yafen Li 1 , Kunwei Shen 1 , Li Zhu 1 1 Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China 2 Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China * These authors have contributed equally to this work Correspondence to: Li Zhu, email: zhuli8@hotmail.com Keywords: breast carcinoma, ductal carcinoma in situ, microinvasion, clinico-pathological feature, prognosis Received: March 13, 2016 Accepted: August 13, 2016 Published: August 26, 2016 ABSTRACT Background: Ductal carcinoma in situ with microinvasion (DCIS-Mi) generally has favorable prognosis, but the long-term outcomes of DCIS-Mi and the biologic evolution from ductal carcinoma in situ (DCIS), DCIS-Mi, to DCIS with T1a breast cancer (DCIS-T1a) has not been specified. The aim of our study was to explore the biological and prognostic features of DCIS-Mi, compared with pure DCIS and DCIS-T1a. Results: After a median follow-up of 31 months, the 3-year estimated disease free survival(DFS) rate of DCIS-Mi patients was significantly lower than that of pure DCIS patients (89.5% vs 97.1%, P=0.009). Patients with DCIS-Mi or DCIS-T1a tumors had comparable 3-year estimated DFS rates (89.5% vs 94.3%, P=0.13). No significant difference in overall survival (OS) was found among different groups (99.6%, 100% and 99.1% for DCIS, DCIS-Mi and DCIS-T1a, P=0.797). In chemotherapy and trastuzumab-naive DCIS-Mi patients, human epidermal growth factor receptor2 (HER2) positivity (HR=21.8, 95%CI, 1.7-286.8, P=0.019) were independent predictor of worse DFS on multivariate analysis. Methods: During September 2002 and December 2014, 602 breast cancer patients who underwent radical surgery were retrospectively reviewed. Three hundred and fifty-nine patients (59.6%) had pure DCIS, 84(14.0%) and 159(26.4%) were diagnosed as DCIS-Mi and DCIS-T1a. Clinico-pathological features were compared between different subgroups. Conclusions: DCIS-Mi displayed a comparable survival to that of DCIS-T1a and a more aggressive biological nature than pure DCIS. Patients with HER2-positive DCIS-Mi had a worse survival and adjuvant chemotherapy plus target therapy needs to be further optimized in those patients.

This study was to investigate the prognostic role of Ki-67 in further classification of triple negative breast cancer (TNBC), and to test whether high expression level of Ki67 can predict benefit from carboplatin. From January 2004 to December 2012, 363 patients operated for TNBC were identified through the institutional clinical database. After a median follow-up time of 34 months (5.2–120.0 months), 62 patients (17.1%) had relapses and 33 patients (9.1%) died of breast cancer. In univariate analysis, high Ki-67 index as well as larger tumor size and lymph node involvement was associated with shorter disease-free survival (DFS) and overall survival (OS). In multivariate analysis, high Ki-67 is an independent risk factor for DFS (Risk Ratio, RR: 2.835, 95% confidence interval, 95% CI: 1.586–5.068, P < 0.001) and OS (RR: 3.180, 95% CI: 1.488–6.793, P = 0.003). When analyzing the 3-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot analysis showed a beneficial effect of carboplatin in patients with high Ki-67 index. In conclusion, TNBC is probably a heterogeneous disease with different characteristics and prognosis, and may be further subdivided according to the Ki-67 expression levels. Patients in the high Ki- 67 group seem to benefit more from treatment with carboplatin, but this needs to be further verified.

Objective The indication of adjuvant chemotherapy recommendation (ACR) in breast cancer patients with intermediate recurrence score (RS) is controversial. This study investigated the relationship between routine clinicopathological indicators and ACR, and established a nomogram for predicting the probability of ACR in this subset of patients. Methods Data for a total of 504 consecutive patients with intermediate RS from January 2014 to December 2016 were retrospectively reviewed. A nomogram was constructed using a multivariate logistic regression model based on data from a training set (378 cases) and validated in an independent validation set (126 cases). A Youden-derived cut-off value was assigned to the nomogram for accuracy evaluation. Results The multivariate logistic regression analysis identified that age, histological grade, tumor size, lymph node (LN) status, molecular subtype, and RS were independent predictors of ACR. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.286. The area under the curve (AUC) values were 0.905 [95% confidence interval (95% CI): 0.876-0.934] and 0.883 (95% CI: 0.824-0.942) in the training and validation sets, respectively. The accuracies of the nomogram for ACR were 84.4% in the training set and 82.1% in the validation set. Conclusions We developed a nomogram to predict the probability of ACR in breast cancer patients with intermediate RS. This model may aid the individual risk assessment and guide treatment decisions in clinical practice.

Danggui Buxue Decoction (DBD), a classical formula of traditional Chinese medicine (TCM), has an impact on promoting hematopoiesis. The aim of our study was to determine whether DBD can prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. We conducted a phase II randomized prospective controlled clinical study. From December 2013 to February 2015, 106 patients were enrolled and randomly assigned (1:1) to the TCM group and control group. The primary end point was incidence of grade 3-4 neutropenia. The secondary end points included incidence of grade 3-4 neutropenia in each cycle, incidence of anemia, and incidence of thrombopenia during 4 cycles. Seventeen patients withdrew from this study, and 89 patients were included in the final analysis. Incidences of grade 3-4 neutropenia during 4 cycles were 57.1% in the TCM group and 59.6% in the control group, and there was no significant difference ( P = .816). Similarly, no significant differences were observed between the 2 groups for incidence of grade 3-4 neutropenia in each cycle. While incidences of anemia were 54.8% and 66.6% for the TCM group and control group, respectively ( P = .280), incidences of thrombopenia were 11.9% for the TCM group and 4.3% for the control group ( P = .248). No significant differences were observed for the incidence of other nonhematological toxicities between the 2 groups. DBD failed to prevent myelosuppression in breast cancer patients treated with adjuvant chemotherapy. Further studies are warranted to validate the efficacy of DBD in selected patients.

Background Increasing human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)/fluorescence in situ hybridisation (FISH) dual-equivocal breast tumours are reported after the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline update. The aim of this study is to investigate the clinico-pathologic characteristics, treatment patterns and disease outcome of these patients with HER2 dual-equivocal tumours. Patients and methods Patients with HER2 IHC 2+ and available FISH results were retrospectively analysed from the Comprehensive Breast Health Center, Shanghai Ruijin Hospital. The 2013 ASCO/CAP guideline was applied to define HER2-positive, dual-equivocal and -negative groups. Patient characteristics, systemic treatment patterns and survival were compared among these groups. Reverse transcriptase-polymerase chain reaction-based assays were applied to test HER2 mRNA expression level. Results Among 691 patients included, 133 (19.25%) were HER2 positive, 25 (3.62%) were HER2 dual-equivocal and 533 (77.13%) were HER2 negative. Univariate and multivariate analyses stated that HER2 dual-equivocal tumours shared more similarity with HER2-negative tumours, whereas HER2-positive tumours had rather different clinico-pathologic features. HER2 dual-equivocal tumours had similar HER2 mRNA levels compared with HER2-negative tumours (P = 0.26), which were much less compared with HER2-positive breast cancer. Besides, adjuvant systemic treatment patterns were comparable between HER2-negative and dual-equivocal tumours, and none of HER2 dual-equivocal patients received anti-HER2 treatment. There was no survival difference among these three groups (P = 0.43). Conclusion HER2 dual-equivocal tumours share more similarity with HER2-negative disease in terms of clinico-pathologic features, HER2 mRNA levels, adjuvant systemic treatment patterns and disease outcome, which deserves further clinical evaluation.

The study aims to identify clinical and pathological factors predictive of disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer (LABC) patients who do not have a pathologic complete response (no-pCR) of primary tumor after neoadjuvant chemotherapy (NC) with vinorelbine/epirubicin (VE) intravenous combination regimen. Retrospectively reviewed data of LABC patients in our Hospital. 97 patients who had no-pCR after NC were identified and enrolled in the study. All patients were treated with three cycles of VE intravenous administration before operation. Local-regional radiotherapy was offered to patients after the completion of chemotherapy followed by hormone therapy according to hormone receptor status. Neoadjuvant chemotherapy consisting of intravenous vinorelbine 25 mg/m on day 1 and 8 plus epirubicin 60 mg/m on day 1 was administered every 3 weeks. The relationship of survival with clinical and pathological factors was evaluated. Univariate analysis (log-rank tests) and multivariate analysis (Cox regression analysis) were performed to identify independent predictors for DFS and OS. Study was analyzed with a median follow-up of 65 months. The 5-year rates for DFS and OS were 58.0 and 68.5 %, respectively. Multivariate analysis revealed that three factors such as the estrogen receptor expression before NC (pre-ER), Ki-67 expression after NC (post-Ki-67), and pathological response of primary tumor (pRT) were independent prognostic factors of LABC patients (pre-ER and pRT for DFS, all three for OS). The DFS at 5 years was 73.8 % for patients without both factors, 51.5 % for patients with any one of both factors, and 10.3 % for patients with both factors. The OS at 5 years was 90.5 % for patients without these three factors, 64.3 % for patients with any one of these three factors, and 30.8 % for patients with any two of these three factors. Patients with all three factors died within 3 years. In LABC patients with no-pCR, three factors independently predicted of survival and, without those three high-risk factors, patients had the promising outcome.

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The aim of the present study was to investigate whether breast cancer patients with changes from positive to negative in the hormone receptor following neoadjuvant chemotherapy (NAC) could benefit from adjuvant endocrine therapy (ET). Between December 2000 and November 2010, 97 eligible patients with a positive-to-negative switch of the hormone receptor status following NAC were identified. All the patients were categorized into two groups on the basis of the administration of ET: 57 ET-administered and 40 ET-naïve patients. Survival analyses were performed to examine the prognostic value of ET administration, as well as other clinical and pathological variables. The administration of ET was associated with a significantly improved disease-free survival (DFS) (P=0.018) in patients with a positive-to-negative switch of the hormone receptor status. The 5-year DFS rates were 77.0 and 55.5% in ET-administered and ET-naïve patients, respectively. The 5-year overall survival (OS) rate for ET-administered was also higher than that of the ET-naïve patients (81.3 vs. 72.7%, P=0.053), but the difference between the two groups did not reach a statistical significance. The present study revealed that patients with the hormone receptor that was altered from positive to negative following NAC benefit from ET, and the hormone receptor status should be evaluated not only in specimens obtained during post-NAC surgery, but also in specimens biopsied prior to NAC.

The programmed death-1 (PD-1) molecule is mainly expressed on functionally "exhausted" CD8(+) T cells, dampening the host antitumor immune response. We evaluated the ratio between effective and regulatory T cells (Tregs) and PD-1 expression as a prognostic factor for operable breast cancer patients. A series of 218 newly diagnosed invasive breast cancer patients who had undergone primary surgery at Ruijin Hospital were identified. The influence of CD8(+) cytotoxic T lymphocytes, FOXP3(+) (Treg cell marker), and PD-1(+) immune cell counts on prognosis was analyzed utilizing immunohistochemistry. Both PD-1(+) immune cells and FOXP3(+) Tregs counts were significantly associated with unfavorable prognostic factors. In bivariate, but not multivariate analysis, high tumor infiltrating PD-1(+) cell counts correlated with significantly shorter patient survival. Our results suggest a prognostic value of the PD-1(+) immune cell population in such breast cancer patients. Targeting the PD-1 pathway may be a feasible approach to treating patients with breast cancer.

Background: Breast cancer is the most diagnosed female cancer and the second leading cause of cancer death in the United States. Triple negative breast cancer (TNBC), a special subtype, defined as breast cancer lacking estrogen, progesterone and HER-2 receptors, showed clinically aggressive features and was associated with poor prognosis. TNBC is resistant to endocrine or HER-2 targeted therapies, and only conventional chemotherapeutic regimens were accepted as the treatment guidelines. Therefore, searching for novel pharmaceutical agents for TNBC is urgent and a hot spot in present clinical research. Teriflunomide, an orally available immunomodulatory drug, approved for treatment of multiple sclerosis (MS) by FDA, has demonstrated the potential application in cancer therapy, such as chronic lymphocytic leukemia (CLL), prostate cancer and melanoma. Therefore, we assessed the therapeutic value of teriflunomide in TNBC cells. Methodology/Principal Findings: In this study, we showed that teriflunomide treatment resulted in a dose- and time-dependent inhibition of proliferation in three TNBC cell lines: MDA-MB-231, MDA-MB-468 and BT549. Meanwhile, the agent could also induce loss of clonogenic survival in dose-dependent fashion in TNBC cells. The analysis of cell cycle distribution by flow cytometry revealed that teriflunomide for 48 h entrapped TNBC cells in S-phase with concomitant reduction in both G1- and G2/M-phase. Furthermore, by Annexin-V/PI staining, we showed high doses of teriflunomide for 2 days led to significant necrosis and minor apoptosis in TNBC cells. Additionally, the effect of teriflunomide on TNBC cell migration and invasion was also tested using Boyden chamber assays. Short-term treatment of teriflunomide decreased the cell motility and invasiveness considerably in a concentration-dependent manner. When evaluated for underlying mechanisms, teriflunomide was found to modulate multiple cell signaling pathways in three TNBC cell lines. First, teriflunomide inhibited expression of proteins linked to cell proliferation, such as cyclin D1 and c-Myc. Second, teriflumomide delayed cell cycle transition by up-regulating cyclin A, along with p27 down-regulation and unchanged cyclin B1. Third, teriflunomide regulated the cell survival proteins, such as up-regulation of BAX and down-regulation of Bcl-Xl, by activation of MAPK pathway. Fourth, teriflunomide suppressed the marker signals involved in epithelial–mesenchymal transition(EMT) and invasion and inhibited activation of FAK/Src complex. Fifth, teriflunomide down-regulated growth factor receptors involved in TNBC growth maintenance, such as EGFR, IGF1R and FGFR4. Conclusion/Significance: Teriflunomide, although an anti-inflammatory agent, is a potent inhibitor of TNBC cells through modulation of multiple signaling pathways and may be of therapeutic benefit for TNBC in clinical practice. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-21.