Primary operation in synchroneous metastasized invasive breast cancer patients: First oncologic outcomes of the prospective randomized phase III ABCSG 28 POSYTIVE trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 557-557 ◽  
Author(s):  
Florian Fitzal ◽  
Marija Balic ◽  
Vesna Bjelic-Radisic ◽  
Michael Hubalek ◽  
Christian F. Singer ◽  
...  

557 Background: The ABCSG 28 Posytive trial compared primary surgery versus primary systemic therapy without surgery in stage IV breast cancer patients. The primary aim was to investigate whether immediate resection of the primary tumor followed by standard systemic therapy improves median survival compared with no surgical resection (NCT01015625). The trial had to be stopped early due insufficient recruitment. Methods: Untreated stage IV breast cancer patients with the primary in situ were randomly assigned to either surgery of the primary versus no surgery followed by systemic therapy between 2011 and 2015 in 15 breast health centers in Austria. Systemic therapy included endocrine therapy or chemotherapy. Patients were routinely followed every 3-6 months. Primary endpoint was median survival. Results: 90 patients (45 with surgery, 45 with primary systemic therapy without surgery) were randomized. Stratification criteria were age, endocrine responsiveness, her2 expression, planned first line therapy and bone only versus other metastases. Patients in the surgery arm had more cT3 breast cancer (22% versus 7%) and more cN2 staging (16% versus 4%) as well as more her2 positive breast cancer cases (27% versus 18%). The median follow up was 37.5 months and immunohistochemical subtype analysis showed 9% basal like, 22% her2 positive, 51% luminal A and 13% luminal B cancers. Both groups were well balanced regarding first line treatment (endocrine versus chemotherapy) however, there were more taxane treated patients in the no surgery group (24.4 versus 15.6%). The median survival in the surgery arm was 34.6 months versus 54.8 months in the no surgery arm without statistical significance (HR 0.691 CI 0.358 – 1.333; p=0.267). Time to distant progression was insignificantly longer in the no surgery arm (surgery arm 13.9 versus no surgery arm 29.0 months). Conclusions: This first analysis of the prospective randomized phase III trial POSYTIVE-ABCSG-28 demonstrated no benefit in overall survival for immediate surgery of the primary in de novo stage IV breast cancer patients. Clinical trial information: NCT01015625.

2020 ◽  
Vol 27 (8) ◽  
pp. 2711-2720 ◽  
Author(s):  
Ross Mudgway ◽  
Carlos Chavez de Paz Villanueva ◽  
Ann C. Lin ◽  
Maheswari Senthil ◽  
Carlos A. Garberoglio ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15092-e15092
Author(s):  
Zhonghua Tao ◽  
Xichun Hu ◽  
Wen-Ming Cao ◽  
Jianxia Liu ◽  
Ting Li ◽  
...  

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB < 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13065-e13065
Author(s):  
Qian Dong ◽  
Mi Zhang ◽  
Da Jiang

e13065 Background: To analyze the correlation between tumor size and metastatic site in first-diagnosed stage IV breast cancer patients. Methods: Stage IV breast cancer patients diagnosed from 2010 to 2015 were screened by the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics of clinical variables were represented by a frequency table, and the Chi-square test was used for comparison. At the same time, the Chi-square test was used to analyze the relationship between tumor size and organ metastasis. Correlation between tumor size and the prognosis of patients was contributed by KM curve and Log-rank test. Results: Regardless of tumor size, the proportion of bone metastasis was higher and brain metastasis was lower in breast cancer patients. There were significant differences in the site of metastases based on different subtype. Luminal A and Luminal B breast cancer had the highest proportion of bone metastases; brain metastasis accounted for the highest proportion in triple-negative breast cancer (TNBC); while the incidence of liver metastasis was the highest in Her-2(+) breast cancer. At the same time, the results indicated that Luminal A breast cancer with a tumor size > 5 cm was more likely to develop multi-site metastasis and lung metastasis, while Luminal B breast cancer with a tumor size ≤ 5 cm was more likely to develop liver metastasis. The results also revealed that TNBC patients with a tumor size of 0 - 2cm were more likely to develop bone metastasis than those with a tumor size > 5 cm, and the incidence of lung metastasis in triple-negative patients showed an increasing trend with the increase of tumor size. Conclusions: Based on subtype, we found that there was a significant difference between tumor size and metastatic site in patients with stage IV breast cancer, and the difference was statistically significant. This study provided evidence-based basis for decision-making of stage IV breast cancer treatment.


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