scholarly journals Clinical characteristics and disease outcomes in ER+ breast cancer: a comparison between HER2+ patients treated with trastuzumab and HER2- patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuai Li ◽  
Jiayi Wu ◽  
Ou Huang ◽  
Jianrong He ◽  
Li Zhu ◽  
...  

Abstract 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 <  0.05). At a median follow-up of 62 months, 443 DFS events and 191 deaths were observed. The estimated 5-year DFS rate was 89.7% in the HER2-neg group and 90.2% in the HER2-pos-T group (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 <  0.001). The estimated 5-year OS rates were 96.0% and 96.3% in the two groups, respectively (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.

2018 ◽  
Vol 49 (3) ◽  
pp. 961-970 ◽  
Author(s):  
Peng Xing ◽  
Huiting Dong ◽  
Qun Liu ◽  
Tingting Zhao ◽  
Fan Yao ◽  
...  

Background/Aims: This study aimed to explore the prognostic value of aldehyde dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with breast cancer. Methods: ALDH1 expression and the presence of VM were examined by immunohistochemistry and CD31/PAS double staining, respectively, using formalin-fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow-up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot survival curves. Prognostic values were assessed by multivariate analysis using the Cox regression model. Results: ALDH1 expression was strongly associated with VM (P = 0.005). ALDH1 expression was positively correlated with histological grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the status of the estrogen receptor and progesterone receptor and were statistically increased in triple-negative breast cancer. Patients with ALDH1 expression or VM displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1-negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM-double-positive patients. ALDH1-positive and VM-positive were independent survival risk factors for DFS and OS. Conclusion: ALDH1 expression and VM are correlated with the survival rate of patients with breast cancer. ALDH1 and VM, either alone or together, are prognostic factors in patients with breast cancer.


1997 ◽  
Vol 15 (6) ◽  
pp. 2329-2337 ◽  
Author(s):  
R Heimann ◽  
D Ferguson ◽  
C Powers ◽  
D Suri ◽  
R R Weichselbaum ◽  
...  

PURPOSE To compare the outcome of African American (AA) and Caucasian (C) breast cancer patients who had equivalent disease extent and were similarly treated. PATIENTS AND METHODS We compared prognostic characteristics, treatment, and outcome of 1,037 C and 481 AA breast cancer patients treated with mastectomy between 1946 and 1987. The median follow-up duration was 15.6 years. RESULTS During the study period, there was a successive increase in the percent of patients who presented with early breast cancer. Between 1980 and 1987, 35.1% AA versus 47.6% C patients had < or = 2-cm tumors and 50.0% AA versus 61.9% C patients were node-negative, while between 1946 and 1959, 27.7% AA and 31.3% C had < or = 2-cm tumors and 41.5% AA versus 40.4% C patients were node-negative. The treatments were similar during the study period. The 20-year disease-free survival (DFS) rate of AA compared with C patients with node-negative < or = 2-cm, 2.1- to 4-cm, and greater than 4-cm tumors and of patients with one to three and > or = four positive nodes was not significantly different. Equal-size tumors had similar proportion of positive axillary nodes in AA compared with C patients. The DFS for AA patients compared with C patients was similar in the periods 1946 to 1959, 1960 to 1969, and 1970 to 1979, but was lower between 1980 and 1987 (P = .02). In multivariable analysis, race was not a significant variable. CONCLUSION In this large group of uniformly treated breast cancer patients, race was not an independent factor that influenced outcome. The racial differences seen between 1980 and 1987 are likely because of a larger percent of greater than 2-cm and node-positive tumors in AA patients. Education and access to early diagnosis should reduce or eliminate the racial differences seen.


Author(s):  
Dong-Jie He ◽  
De-Quan Yu ◽  
Qi-Ming Wang ◽  
Zong-Yan Yu ◽  
Yu-Hong Qi ◽  
...  

Background Brain metastasis is an important cause of breast cancer-related death. Aim We evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis. Methods The Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan–Meier method was used to compare survival outcomes according to breast cancer subtype. Results Among 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2– breast cancer, HR–/HER2– breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99–3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2−, 19 months for HR+/HER2+, 11 months for HR−/HER2+, and 6 months for HR–/HER2– ( P < .0001). Relative to HR+/HER2– breast cancer, HR–/HER2– breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy ( p for interaction = .005). Conclusions Breast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.


2018 ◽  
Vol 3 (1) ◽  
pp. 33
Author(s):  
Harissa Husainy Hasbullah ◽  
Anita Bustamam ◽  
Tho Lye Munn ◽  
Vincent Phua

Introduction: Adjuvant trastuzumab has been used in human epidermal growth factor-2 (HER2) breast cancer to improve survival but with concern of cardiotoxicity. Our study is the first to review efficacy and toxicity of adjuvant trastuzumab in Malaysia. Methods: This is a retrospective cohort study on HER2 non metastatic breast cancer patients in University Malaya Medical Centre diagnosed between October 2006 and May 2011. Two cohorts were created based on whether or not they received adjuvant trastuzumab. Disease free survival (DFS) and overall survival (OS) for both groups were estimated using Kaplan Meier method and compared using Log rank test. Cox proportional hazards regression models analysed for potential covariates of age, tumour size and grade, node and estrogen receptor (ER) status. Trastuzumab cardiotoxicity was defined as left ventricular systolic dysfunction or heart failure with or without symptoms and graded using Common Terminology Criteria for Adverse Events (CTCAE 4.0). Results: 170 HER2 non metastatic breast cancer patients were identified. Thirty-three received trastuzumab and 136 did not. Median age was 53.4 ± 10.3 years old. Significantly more ER negative patients received trastuzumab. Four years DFS in ‘trastuzumab’ versus ‘no trastuzumab’ cohort was 90.9% vs 74.5% (p = 0.027). Four years OS was 91% vs 84.7% (p = 0.30) respectively. Majority tolerated trastuzumab with no toxicity. Five patients (15.2%) experienced cardiotoxicity (all grade I).Conclusions: Adjuvant trastuzumab significantly improved DFS in HER2 breast cancer. Treatment was well tolerated. With this we propose the justification for adjuvant trastuzumab in HER2 breast cancer in our population.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12550-e12550
Author(s):  
Aimaz Afrough ◽  
Heather Lin ◽  
Angelica M. Gutierrez-Barrera ◽  
Jennifer Keating Litton ◽  
Vicente Valero ◽  
...  

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.


2018 ◽  
Vol 90 ◽  
pp. 92-101 ◽  
Author(s):  
G.M.H.E. Dackus ◽  
K. Jóźwiak ◽  
G.S. Sonke ◽  
E. van der Wall ◽  
P.J. van Diest ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14028-e14028 ◽  
Author(s):  
Xuefei Wang ◽  
Guochao Zhang ◽  
Qiang Sun

e14028 Background: Nowadays programmed cell death (ligand) 1 (PD1/PD-L1) inhibitors in the clinic show benefit for appropriate patient. There are clinical trials for specific breast cancer patients. We all know that the prognosis of breast cancer is associated with CTC. However, PD-L1 expression on circulating tumor cells (CTC) is lack of research. It is crucial for the prediction and supervision of molecular-targeted therapy, while the predictive biomarker response to PD(-L)1 checkpoint inhibitors is lacking. So we tried to explore the relationship between overexpression of PD-L1 on CTCs and prognosis and clinicopathological features of breast cancer patients. Methods: We analyzed CTC and PD-L1 mRNA expression on CTC in 20 primary breast cancer patients, through mRNA probe hybridization. The relationship between clinicopathological features and PD-L1 expression on CTC was analyzed by chi square test. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with low PD-L1 expression. Results: The median follow-up time was 40 months (range, 36-43 months). Of the 20 patients, 15 had more than 1 CTC in 7.5ml peripheral blood. Among the 15 patients, each one has at least 1 CTC showing PD-L1. The expression of PD-L1 on CTC was divided into low expression, medium expression and high expression, then we gave 1 score for low expression, 2 score for medium expression and 3 score for high expression. PD-L1 high expression was total score≥3, while PD-L1 low expression was total score < 3. We found PD-L1 expression on CTC is related to the tumor size(P = 0.012) lymph node status (P = 0.001) and PR status (P = 0.037). There was significant difference between T2 and T3 in large tumor group(P = 0.003), while in node status group statistical difference can be found in N1 vs N3(P = 0.000) and N2 vs N3(P = 0.015). Our data indicated that patients with high PD-L1 expression on CTC had poor overall survival(P = 0.004) compared to low PD-L1 expression on CTC (Table). Univariate Cox proportional hazards model analysis showed that high PD-L1 expression on CTC was an independent prognostic factor. Conclusions: PD-L1 on CTC is indeed associated with some poor clinicopathological features. High expression of PD-L1 on CTC is an independent prognostic factor for shorter survival. [Table: see text]


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Hyelin Na ◽  
Jinil Han ◽  
Na-Lee Ka ◽  
Min-Ho Lee ◽  
Yoon-La Choi ◽  
...  

Abstract Background Nuclear receptor subfamily 1, group D, member 1 (NR1D1) is a ligand-regulated nuclear receptor and transcriptional factor. Although recent studies have implicated NR1D1 as a regulator of DNA repair and proliferation in breast cancers, its potential as a therapeutic target for breast cancer has not been assessed in terms of clinical outcomes. Thus, this study aims to analyze NR1D1 expression in breast cancer patients and to evaluate its potential prognostic value. Methods NR1D1 expression was analyzed by immunohistochemistry using an anti-NR1D1 antibody in 694 breast cancer samples. Survival analyses were performed using the Kaplan–Meier method with the log-rank test to investigate the association of NR1D1 expression with clinical outcome. Results One hundred thirty-nine of these samples exhibited high NR1D1 expression, mostly in the nucleus of breast cancer cells. NR1D1 expression correlated significantly with histological grade and estrogen receptor status. Overall survival (OS) and disease-free survival (DFS) did not correlate significantly with NR1D1 expression in breast cancer patients regardless of whether they had received chemotherapy. Subgroup analysis performed according to molecular subtype of breast cancer showed a significant influence of high NR1D1 expression on OS (P = 0.002) and DFS (P = 0.007) in patients with triple-negative breast cancer (TNBC) treated with chemotherapy. Conclusions High NR1D1 expression level had a favorable impact on OS and DFS in patients with TNBC treated with chemotherapy. NR1D1 should be investigated further as a possible prognostic marker in TNBC patients receiving chemotherapeutic treatment and as a target in the development of chemotherapeutic approaches to treating TNBC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 501-501
Author(s):  
Eleftherios P. Mamounas ◽  
Hanna Bandos ◽  
Priya Rastogi ◽  
Yi Zhang ◽  
Kai Treuner ◽  
...  

501 Background: The BCI HOXB13/IL17BR ratio (BCI-H/I) has been shown to predict endocrine tx (ET) and extended ET (EET) benefit. We examined the effect of BCI-H/I for EET benefit prediction in NSABP B-42, evaluating extended letrozole tx (ELT) in HR+ breast cancer patients (pts) who completed 5 yrs of ET. Methods: All pts with available primary tumor tissue were eligible. Primary endpoint was recurrence-free interval (RFI). Secondary endpoints were distant recurrence (DR), breast cancer-free interval (BCFI), and disease-free survival (DFS). Stratified Cox proportional hazards model was used. Due to a non-proportional effect of ELT on DR, time-dependent secondary analyses (≤4y, >4y) were performed. Likelihood ratio test evaluated treatment by BCI-H/I interaction. Results: In 2,179 pts analyzed (60% N0; 62% AI only; 80% HER2-), 45% were BCI-H/I-High and 55% BCI-H/I-Low. ELT showed an absolute 10y benefit of 1.6% for RFI (HR=0.77, 95% CI 0.57-1.05, p=0.10) (BCI-H/I-Low: 1.1% [HR=0.69, 0.43-1.11, p=0.13]; BCI-H/I-High: 2.4% [HR=0.83, 0.55-1.26, p=0.38]; interaction p=0.55). There was no statistically significant ELT by BCI-H/I interaction for BCFI (BCI-H/I-Low: HR=0.53, 0.36-0.78, p=0.001; BCI-H/I-High: HR=0.85, 0.60-1.21, p=0.36; interaction p=0.07) or for DFS (BCI-H/I-Low: HR=0.75, 0.58-0.95, p=0.017; BCI-H/I-High: HR=0.81, 0.64-1.04, p=0.09; interaction p=0.62). Before 4y, there was no statistically significant ELT benefit on DR in either BCI-H/I group. After 4y, BCI-H/I-High pts had statistically significant ELT benefit on DR (HR: 0.29, 0.12-0.69, p=0.003), while BCI-H/I-Low pts were less likely to benefit (HR: 0.68, 0.33-1.39, p=0.28) (interaction p=0.14). Conclusions: BCI-H/I prediction of ELT benefit on RFI was not confirmed. In time-dependent DR analyses, BCI-H/I-High pts had statistically significant benefit from ELT after 4y, while BCI-H/I-Low pts did not. Observed ELT benefit on BCFI in BCI-H/I-Low pts was primarily driven by second primary breast cancers. Additional follow-up is needed to further characterize BCI-H/I predictive ability in this study. Support: U10CA180868, -180822, U24CA196067; Novartis; Biotheranostics. Clinical trial information: NCT00382070. [Table: see text]


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