HEAT-SHOCK PROTEINS HSP27 AND HSP70 - LACK OF CORRELATION WITH RESPONSE TO TAMOXIFEN AND CLINICAL COURSE OF DISEASE IN ESTROGEN RECEPTOR-POSITIVE METASTATIC BREAST-CANCER (A SOUTHWEST-ONCOLOGY-GROUP STUDY)
Dr. Ciocca et al., HEAT-SHOCK PROTEINS HSP27 AND HSP70 - LACK OF CORRELATION WITH RESPONSE TO TAMOXIFEN AND CLINICAL COURSE OF DISEASE IN ESTROGEN RECEPTOR-POSITIVE METASTATIC BREAST-CANCER (A SOUTHWEST-ONCOLOGY-GROUP STUDY), Clinical cancer research, 4(5), 1998, pp. 1263-1266
In this study, we tested the hypothesis that heat shock proteins (hsps
) 27 and 70 are associated with clinical resistance to tamoxifen. hsp2
7 is, like progesterone receptor, an estrogen-regulated protein. hsp70
is also of interest because of its interaction with estrogen receptor
s and because hsp70 is a component of the molecular chaperone machiner
y functioning in the assembly and trafficking of steroid receptors, In
addition, hsps in general help protect cells against noxious stimuli
and stress, and their expression has been linked to drug resistance. T
he study involved 205 tumors from estrogen receptor-positive tamoxifen
-treated breast cancer patients with metastatic disease. All patients
received daily tamoxifen as initial therapy for metastatic disease. Th
e study began in 1982, and follow-up is now 9 years. hsp27 and hsp70 w
ere detected by immunohistochemistry and scored according to the nucle
ar and/or cytoplasmic content, Expression of hsp27 or hsp70 was unrela
ted to estrogen receptor content, progesterone receptor content, menop
ausal status, age, and presence of visceral disease. Cytoplasmic and n
uclear hsp27 positivities were weakly and inversely related to each ot
her (P = 0.05), There was a significant association between cytoplasmi
c hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between
nuclear hsp70 and nuclear hsp27 content (P = 0.001), Cytoplasmic and n
uclear hsp70 were also associated (P = 0.02), However, increased hsp27
and hsp70 expression (nuclear or cytoplasmic) was not significantly a
ssociated with response to tamoxifen, time to treatment failure, or su
rvival. Thus, this study clarifies the lack of clinical utility of hsp
27 and hsp70 in predicting the response to tamoxifen in an estrogen re
ceptor-positive breast cancer population.