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conferenceseries.com
Volume 2, Issue 3 (Suppl) Breast Can Curr Res, an open access journal
ISSN: 2572-4118 Breast Cancer 2017
June 15-17, 2017
June 15-17, 2017 London, UK
5th World Congress on
Breast Cancer
Breast Can Curr Res 2017, 2:3(Suppl)
DOI: 10.4172/2572-4118-C1-006
Glucose regulated protein (GRP-78)-mediated selective phosphorylation of Akt on threonine 308
sensitizes breast cancer cells to tamoxifen-induced cytotoxicity.
Radha Pujari
Savitribai Phule Pune University, India
Breast cancer is the most prevalent cancer in women. Tamoxifen (TAM) has been used for several years as an effective drug
for treating estrogen receptor positive breast tumors. However, resistance to TAM is a major challenge in treatment of breast
cancer. Accumulating evidence has highlighted the role of Glucose-regulated protein (GRP)-78, the master regulator of the
unfolded protein response, in chemoresistance. The present study aimed to decipher the function of GRP78 during response
to TAM in breast cancer cells. Among a panel of drugs -paclitaxel, doxorubicin, 5-fluorouracil, UCN-01 and tamoxifen, only
TAM induced apoptosis and up-regulated the expression of GRP78 in MCF-7 and MDA-MB-231 cell lines. Inhibition of
GRP78 augmented apoptosis and overexpression rendered the cells resistant suggesting a decisive role for GRP78 in TAM-
mediated cytotoxicity. Mechanistically, TAM selectively unregulated phosphorylation of Akt on Thr308 but not on Ser473,
and silencing of GRP78 resulted in inhibition of Akt (Thr308) phosphorylation. GRP78 inhibition prevented TAM-induced
phosphorylation of GSK3β, a downstream substrate of Akt implicating a role for GRP78 in TAM-induced Akt activation.
Additionally, our study demonstrated a physical association of Akt and GRP78 that may be decisive for cell survival. The
present study identifies a crucial role for GRP78 and Akt-mediated survival mechanism during TAM-induced response in
breast cancer cells. The findings provide evidence for the protective function of GRP78 in stressed cells to promote drug
resistance and suggest that a combination of compounds targeting GRP78 and anticancer drugs like TAM would be beneficial
to overcome therapy resistance.
A series study on brain metastasis for breast cancer
Shikai Wu
Academy of Military Medical Sciences, China
Brain metastasis is the principle cause of death for breast cancer, we have conducted a series of studies on the occurrence,
development, and treatment of breast cancer brain metastasis. Firstly, we analyze the clinical characteristics and prognostic
factors of breast cancer patients with brain metastases, and found that WBRT+SRS is better thanWBRT alone in multiple brain
metastases, SRS alone can replace WBRT+SRS used in patients with less than three brain metastases. We also constructed a
nomogram for predicting 1st and 2nd year overall survival, which exhibited good accuracy in predicting overall survival.
Secondly, we investigated the risk and relapse of perihippocampal (PH) metastases in breast cancer, and found that hippocampal
metastases were identified in 1.2% of metastases and 4.1% of patients. pH lesions comprised 3.5% of lesions in 11.1% of
patients. The risks of PHmetastasis recurrence were 4.6% for WBRT and 6.8% for sub-therapeutic irradiation in the pH region.
Thirdly, we invested the characteristics of cystic BM in a large cohort of breast cancer patients and found patients with cystic
metastasis were characterized by a larger metastasis volume, a shorter progression-free survival (PFS) following their first
treatment for BM, and poor overall survival after BM (p<0.05). This study shows that cystic BM from breast cancer, a special
morphological type of BM, had worse prognosis than the more commonly observed solid BM. Fourthly, we revealed that
reirradiation is an effective and a safe treatment for patients with brain metastases from breast cancer. Patients with a high KPS
score, stable extracranial metastasis and good response to reirradiation might be benefit from reirradiation, whereas patients
with peritumoral edema, cystic brain metastasis and a low KPS score might not be appropriate candidates for reirradiation.