Abstract:
http://breast-cancer-research.com/content/11/5/R69
Article:
http://breast-cancer-research.com/co...df/bcr2363.pdf
Of interest (pp. 15 - 17 of article):
" . . . in a cohort of 1731 breast cancer patients treated with varying neoadjuvant antrhacycline-based regimes that ER+/Her2+ carcinomas had a higher pCR rate thatn ER+/Her2- tumors (15.3% vs. 6%). The hightest pCR rates in this study were observed in ER-/Her2+ (29%) and in ER-/Her2- carcinomas (22.4%). 5 year disease-free survival was only slightly lower in ER+/Her2+ than in ER+/Her2- tumors (66.3% vs. 60.2%) and was lowest in ER-/Her2+ tumors (43.7%) . . .
"Regarding these results and our data presented here, it is conceivable that patients with HR and Her2 co-expressing breast carcinomas might constitute a group that particularly benefits from neoadjuvant chemotherapy as demonstrated by high pCR rates and favorable survival times. This is in contrast to HR+/Her2- tumors that rarely respond but nevertheless show favorable suvival rates. The results according to the response rate of HR-/Her2+ tumors are conflictive as the studies cited above found high pCR rates in this subgroup, in contrast to our results. Of note, neither in the Gepardou cohort nor in the cohorts described above trastuzumab had been included in the neoadjuvant therapy regime as this was no standard at the time of study execution. As newer studies using trastuzumab in patients with Her2+ tumors have shown doubled pCR rates, it will be compelling to elucidate whether the predictive and prognostic effects described above would be altered by the addition of anti-Her2 agents.
"Some interesting facts about the molecular interaction of hormone receptors (particularly ER) and Her2 have been reported to date: estrogen generally downregulates Her2 expression, a mechanism that does not seem relevant in HR/Her2 co-expressing carcinomas from hitherto unknown reasons. Moreover, ER can activate Her2 by membrane non-genomic estrogen signaling, while Her2 activates ligand-independently ER by mitogen-activated protein kinase (MAPK)-/protien kinase B (AKT)-mediated phosphorylation. These interactions have been supposed to be underlying the relative resistance and worse prognosis of breast cancers that co-express ER and Her2 and that have been treated with Tamoxifen. However, the situation in patients that are treated with primary chemotherapy is presumably quite different and there are no functional data that explicity refer to this group of tumors. In the adjuvant setting Her2+ tumors respond well to an anthracycline-based therapy and it is conceivable that this might also be the case in HR+/Her2+ tumors in the neoadjuvant setting as reflected by high pCR rates. For long-term prognosis, the phenotype of HR positive tumor cells (higher differentiation, slower proliferation, etc.) seems to be more relevant in receptor co-expressing tumors and may even be amplified by Her2-mediated ER activation. Yet, the exact mechanisms remain to be elucidated in future functional studies."
Hopeful
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