Potential protein markers for breast cancer recurrence: a retrospective cohort study

Abstract

Background We evaluated five key proteins involved in various cancer-related pathways and assessed their relation to breast cancer recurrence. Methods We used the Kentucky Cancer Registry to retrospectively identify primary invasive breast cancer cases (n=475) that were diagnosed and treated at University of Kentucky Medical Center between 2000 and 2007. Breast cancer recurrence was observed in 62 cases during the five-year followup after diagnosis. Protein expression or activity level was analyzed from surgery tissue using immunohistochemical assays. Results Compared to ER+/PR+/HER2- patients without recurrence, those with recurrence had higher TWIST expression (p=0.049) but lower ABL1/ABL2 activity (p=0.003) in primary tumors. We also found that triple-negative breast cancer patients with recurrence had higher SNAI1 expression compared to those without recurrence (p=0.03). After adjusting for potential confounders, the higher ABL1/ABL2 activity in primary tumors was associated with a decreased risk of recurrence (OR=0.72, 95%CI = 0.85-0.90) among ER+/PR+/HER2- patients. In addition, among patients with recurrence we observed that the activity level of ABL1/ABL2 was significantly increased in recurrent tumors compared to the matched primary tumors regardless of the subtype (p=0.013). Conclusions These findings provide evidence that the expression/activity level of various proteins may be differentially associated with risk of recurrence of breast tumor subtypes.

Enabling Tumor Growth and Progression: Recent Progress in Unraveling the Functions of ABL Kinases in Solid Tumor Cells

“…Phosphorylated ABL1 also was identified as a protein associated with hepatocellular carcinoma early recurrence, using western blotting with primary tumor pools from 80 patients and 192 different antibodies [103]. Moreover, a recent study using a large population-based sample of primary breast cancers (discussed below; currently in-review) demonstrates that low/negative ABL1/ABL2 activities in primary luminal A breast cancers is associated with eventual recurrence/metastasis, and ABL1/ABL2 activities are subsequently elevated in the matched recurrent/metastatic samples [104]. …”

“…The researchers tested whether ABL kinase activities are altered during breast cancer progression using a population-based sample of breast cancer cases (patients diagnosed/treated from 2000–2007; n=475) [104]. Interestingly, ABL1/ABL2 activities (pCRKL, IHC), were low/negative in ER + /PR + tumors (at the time of diagnosis) from patients who eventually developed a recurrence/metastasis as compared to primary tumors (at diagnosis) from patients who did not recur [104]. Moreover, ABL1/ABL2 activities were dramatically elevated in the matched recurrent samples [104].…”

“…Interestingly, ABL1/ABL2 activities (pCRKL, IHC), were low/negative in ER + /PR + tumors (at the time of diagnosis) from patients who eventually developed a recurrence/metastasis as compared to primary tumors (at diagnosis) from patients who did not recur [104]. Moreover, ABL1/ABL2 activities were dramatically elevated in the matched recurrent samples [104]. In contrast, in the basal-like, triple-negative subtype, there was a trend towards elevated ABL1/ABL2 activities in the primary tumors from patients that recurred as compared to those that did not recur, and ABL1/ABL2 activities were further increased in 3/4 recurrent/metastatic samples.…”

“…A manuscript currently under review also demonstrates striking differences between ABL kinase activities in ER + /PR + and triple-negative subtypes. The researchers tested whether ABL kinase activities are altered during breast cancer progression using a population-based sample of breast cancer cases (patients diagnosed/treated from 2000–2007; n=475) [104]. Interestingly, ABL1/ABL2 activities (pCRKL, IHC), were low/negative in ER + /PR + tumors (at the time of diagnosis) from patients who eventually developed a recurrence/metastasis as compared to primary tumors (at diagnosis) from patients who did not recur [104].…”

“…We thank Drs. Tom Tucker, Chunyan He, Chi Wang, Vivek Rangnekar, Chunming Liu, Rachel Stewart, Bin Huang, and Binhua Zhou for allowing us to describe data from their manuscript that is under review [104].…”