scholarly journals In Real Life, Low-Level HER2 Expression May Be Associated With Better Outcome in HER2-Negative Breast Cancer: A Study of the National Cancer Center, China

2022 ◽  
Vol 11 ◽  
Author(s):  
Yiqun Li ◽  
Nilupai Abudureheiyimu ◽  
Hongnan Mo ◽  
Xiuwen Guan ◽  
Shaoyan Lin ◽  
...  

BackgroundTo characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.MethodsThe China National Cancer Center database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).ResultsThere were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%, p < 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months, p = 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months, p = 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months, p = 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73–0.98, p = 0.026).ConclusionOur findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.

Author(s):  
Fitri Wulandari ◽  
Kartika Widayati ◽  
Fita Rahmawati

Breast cancer is the cancer with the most prevalence of 43.3% and the mortality rate that reaches 12.9%. The prognosis of breast cancer can be affected by diabetes mellitus (DM), so that efforts to control DM through antidiabetic therapy are very necessary, but antidiabetic therapy is also reported to be associated with the prognosis of breast cancer. The purpose of this study was to determine the relationship of diabetes and antidiabetic use to recurrence in breast cancer patients. This study used a retrospective cohort design, involving 176 female non-metastatic breast cancer patients who received chemotherapy, consisting of 88 patients with DM and 88 non-DM patients. The exposures in the study were diabetes mellitus and the types of antidiabetic drugs (metformin and non metformin based therapy), while the study output was the recurrence of breast cancer. The research data was obtained from the patient’s medical records at RSUP Dr. Sardjito Yogyakarta. Research analysis used Chi-square, Kaplan Meier method and Cox-regression to estimate Hazard Ratio with 95% confidence interval. The results showed DM in breast cancer patients was associated with increased the risk of recurrence (HR 2,458; 95% CI 1,571-3,846, log rank test P=0,000), while the use of antidiabetic types (metformin and nonmetformin) to control DM in breast cancer patients was not associated with the risk of recurrence (HR 1.391; 95% CI 0.816 - 2.370, log rank test P=0.210). Further research is warranted by monitoring blood glucose levels regularly.


2021 ◽  
Vol 13 ◽  
pp. 175883592098765
Author(s):  
Marion Bertho ◽  
Julien Fraisse ◽  
Anne Patsouris ◽  
Paul Cottu ◽  
Monica Arnedos ◽  
...  

Background: Bone-only (BO) metastatic breast cancer (MBC) is considered a more favorable entity than other MBC presentations. However, only few retrospective series and data from selected randomized controlled trials have been reported so far. Methods: Using the French national multicenter ESME (Epidemiological Strategy and Medico Economics) Data Platform, the primary objective of our study was to compare the overall survival (OS) of patients with BO versus non-BO MBC at diagnosis, with adjustment on main prognostic factors using a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1), describe treatment patterns, and estimate factors associated with OS. Results: Out of 20,095 eligible women, 5041 (22.4%) patients had BO disease [hormone-receptor positive (HR+)/human epidermal growth-factor-receptor-2 negative (HER2−), n = 4 102/13,229 (31%); HER2+, n = 644/3909 (16.5%); HR−/HER2−, n = 295/2 957 (10%)]. BO MBC patients had a better adjusted OS compared with non-BO MBC [52.1 months (95% confidence interval (CI) 50.3–54.1) versus 34.7 months (95% CI 34.0–35.6) respectively]. The 5-year OS rate of BO MBC patients was 43.4% (95% CI 41.7–45.2). They also had a better PFS1 [13.1 months (95% CI 12.6–13.8) versus 8.5 months (95% CI 8.3–8.7), respectively]. This observation could be repeated in all subtypes. BO disease was an independent prognostic factor of OS [hazard ratio 0.68 (95% CI 0.65–0.72), p < 0.0001]. Results were concordant in all analyses. Conclusion: BO MBC patients have better outcomes compared with non-BO MBC, consistently, through all MBC subtypes.


2004 ◽  
Vol 22 (16) ◽  
pp. 3302-3308 ◽  
Author(s):  
Fabrice Andre ◽  
Khemaies Slimane ◽  
Thomas Bachelot ◽  
Arianne Dunant ◽  
Moise Namer ◽  
...  

Purpose Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. Patients and Methods A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis. Results Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001). Conclusion The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abby B. Statler ◽  
Brian P. Hobbs ◽  
Wei Wei ◽  
Annie Gupta ◽  
Cassann N. Blake ◽  
...  

AbstractTreatment patterns and outcomes are unclear for metastatic breast cancer (MBC) patients diagnosed with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) disease. This study aimed to: (1) examine the utilization of first-line therapy among HR+/HER2+/MBC patients and (2) compare overall survival (OS) between the identified regimens. We analyzed National Cancer Database patients (HR+/HER2+/MBC) who were treated between 2010 and 2015. Multivariable logistic and Cox regression were used to: (1) identify independent predictors of treatment receipt and (2) determine significant prognostic factors for OS. Kaplan-Meier method and log-rank test were used to estimate and evaluate OS, respectively. Propensity scores were added to all multivariate OS models, thereby accounting for bias in treatment receipt. Of 6,234 patients analyzed, 3770 (60.5%) received hormonal therapy and 2464 (39.5%) received chemotherapy. Receipt of hormonal therapy was associated with older age, grade 1/grade 2 disease, no visceral involvement, higher comorbidity scores, and being white. Multivariate analysis suggest patients receiving hormonal therapy + anti-HER2 experienced improved OS, when compared to chemotherapy + anti-HER2 (HR: 0.74, p = 0.004). Overall, the cohort receiving hormonal therapy + anti-HER2 reported the highest 5-year OS (hormonal + anti-HER2: 47.5% vs. chemotherapy + anti-HER2: 39.8% vs. hormonal: 38.5% vs. chemotherapy: 36.3%, p < 0.001). Our findings suggest de-escalated therapy may be the preferred and potentially more effective care path for HR+/HER2+/MBC patients, signaling a need for randomized studies.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published and public microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified significant differential expression of the gene encoding the Wnt pathway molecule dishevelled-3, DVL3 (5-7), in the primary tumors of breast cancer patients treated with trastuzumab. DVL3 expression in primary tumors of the breast in patients treated with trastuzumab was significantly higher than in patients not treated with trastuzumab.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the deleted in colorectal cancer locus DCC (5, 6) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment with trastuzumab.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1052-1052
Author(s):  
Kelvin K H Bao ◽  
Leone Sutanto ◽  
Shirley S W Tse ◽  
Ka Man Cheung ◽  
Jeffrey C H Chan

1052 Background: Markers for the efficacy of CDK4/6 inhibitor in estrogen receptor (ER) positive, HER2 negative advanced breast cancer are limited. The bidirectional crosstalks that exist between ER and HER2 pathways contribute to endocrine resistance. We investigated the association between low levels of HER2 expression and the clinical outcome of patients with ER+ HER2- metastatic breast cancer (MBC) treated with CDK4/6 inhibitors. Methods: We identified consecutive patients with ER+ HER2- MBC who received CDK4/6 inhibitor plus either letrozole or fulvestrant between Mar 2017 - Jun 2020 from an institutional cancer registry. HER2-low expression was defined as IHC score 1+, or 2+ with a negative ISH. Progression-free survival (PFS) was defined as the time from the initiation of CDK4/6 inhibitor to the date of radiological or clinical progression, or death. The relationship between HER2 expression levels and PFS was evaluated using log-rank test and multivariable Cox regression modelling. Results: 106 women with MBC were eligible for analysis. Median age at treatment was 58 (23.0-91.4). The majority received palbociclib (84%) while the rest received ribociclib. CDK4/6 inhibitor was used as first-line treatment in 50.9% of cases. Most tumors were of ductal histology (83%) and progesterone receptor (PgR) positive (84.9%), and 22.6% of the patients had bone-only disease. 77.3% of cases were considered HER2-low expressing. HER2-low expression was associated with a significantly shorter PFS compared with HER2 IHC 0 counterpart (median, 8.9 vs 18.8 months, p= 0.014). In multivariate analysis, HER-2 low expression remained significantly associated with an inferior PFS (HR 1.96, 95%CI 1.03-3.75, p= 0.041) after adjusting for the line of treatment, PgR status and disease extent (bone only vs extra-osseous disease). Conclusions: In patients with ER+ HER2- MBC treated with CDK4/6 inhibitors, HER2-low expression was associated with an inferior PFS, and may serve as a potential marker candidate for CDK4/6 inhibitor efficacy. As novel anti-HER2 antibody-drug conjugates demonstrated efficacy in HER2-low expressing MBC, coupled with the emerging evidence for the combination of CDK4/6 inhibitors with anti-HER2 agents, this HER2-low expression subgroup warrants prospective evaluations in future trials.


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