Background: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR,
and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among
breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a
considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling
pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the
most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to
specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS
signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.
Methods: The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85
invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018–
2019, and its association with the clinicopathologic variables of patients was evaluated.
Results: HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor
tissue of patients with breast cancer. Moreover, this study observed a significant association between the high
expression of SIAH2/ HSP90 with ER status, high expression of HSP90 with Recurrence/ Metastasis, and
high expression of SIAH2 with Ki-67 proliferation index.
Conclusion: The HSP90 and SIAH2 expressions play a significant role in breast cancer development by
combining the experimental and clinical data obtained from the literature.