HER2 Support Group Forums - View Single Post - ER+, HER2+

Hopeful · 10-16-2008, 07:12 AM

Margerie,

Thanks for digging up that abstract; I have it in my files but could not locate it easily.

Debbie,

Here is an abstract to an interesting article (which is only available in full for a fee) concerning the eitiology of triple positive bc: http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Basically, it says the older you get, the more likely you are to be ER+/PR+ and the less likely you are to be Her2+, however, they found that triple positive women were dx at a younger age than women with any other ER/PR Her2 phenotype, at a median age of 52.4 years.

They say (and I must add, these are Belgian researchers writing a paper in English, which is not their first language):

"The proportion of breast cancers beint ER+Her2+ is low, representing only 6.2% of all breast cancers in our series. . . Although our findings are hypthesis generating and awaiting to be confirmed, the reason why the small group of ER+PR+Her2+ lesions appear early in life is as yet unclear. However, our findings incorporate some of the interesting biology of Her2+ breast cancers and may shed light on the carcinogenic mechanisms for early-onset of ER+Her2+ brease cancers as opposed to ER+ Her2- cases. We suggest that high estrogen levels in young women drive ER to predominantly regulate classic ER regulated genes such as PR expression independent of Her2 whereas in postmenopausal women, low estrogen levels may allow an increasing effect of growth factor signalling on ER action resulting in a different set of ER regulated genes being expressed with a lower likelihood for PR expression. Otherwise said, at young age, Her2+ breast cancers are more likely ER+ through the presence of elevated estrogen levels whereas with aging and decreasing estrogen levels, the growth of Her2+ breast cancers is less dependent of estrogens. This is also reflected in the younger age onset of PR+ compared with PR- lesions which is mainly due to the PR+ Her2+ subgroup. The biology behind this suggests that premenopausal steriods select ER+ breast cancers to appear earlier if they are PR+Her2+ than if they are PR-Her2-, PR-Her2+ or PR+ Her2-. . . . It is well known that hormonal risk factors are different by the ER expression of breast cancer, but the drive or risk factors behind the earlier appearance of ER+Her2+ cases compared with other tumour types remains to be explored."

In my reading, it also appears that two principles are emerging: tamoxifen upregulates Her2, while herceptin upregulates ER. I think the key to long survival for triple positives is extended therapy which maintains a balance in the tension between these two opposing bc pathways. Again, I am not any type of medical professional, just what I consider to be a well read patient, and these are my opinions and no more than that.

Hopeful

10-16-2008, 07:12 AM	#18
Hopeful Senior Member Join Date: Aug 2006 Posts: 3,380	Margerie, Thanks for digging up that abstract; I have it in my files but could not locate it easily. Debbie, Here is an abstract to an interesting article (which is only available in full for a fee) concerning the eitiology of triple positive bc: http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract Basically, it says the older you get, the more likely you are to be ER+/PR+ and the less likely you are to be Her2+, however, they found that triple positive women were dx at a younger age than women with any other ER/PR Her2 phenotype, at a median age of 52.4 years. They say (and I must add, these are Belgian researchers writing a paper in English, which is not their first language): "The proportion of breast cancers beint ER+Her2+ is low, representing only 6.2% of all breast cancers in our series. . . Although our findings are hypthesis generating and awaiting to be confirmed, the reason why the small group of ER+PR+Her2+ lesions appear early in life is as yet unclear. However, our findings incorporate some of the interesting biology of Her2+ breast cancers and may shed light on the carcinogenic mechanisms for early-onset of ER+Her2+ brease cancers as opposed to ER+ Her2- cases. We suggest that high estrogen levels in young women drive ER to predominantly regulate classic ER regulated genes such as PR expression independent of Her2 whereas in postmenopausal women, low estrogen levels may allow an increasing effect of growth factor signalling on ER action resulting in a different set of ER regulated genes being expressed with a lower likelihood for PR expression. Otherwise said, at young age, Her2+ breast cancers are more likely ER+ through the presence of elevated estrogen levels whereas with aging and decreasing estrogen levels, the growth of Her2+ breast cancers is less dependent of estrogens. This is also reflected in the younger age onset of PR+ compared with PR- lesions which is mainly due to the PR+ Her2+ subgroup. The biology behind this suggests that premenopausal steriods select ER+ breast cancers to appear earlier if they are PR+Her2+ than if they are PR-Her2-, PR-Her2+ or PR+ Her2-. . . . It is well known that hormonal risk factors are different by the ER expression of breast cancer, but the drive or risk factors behind the earlier appearance of ER+Her2+ cases compared with other tumour types remains to be explored." In my reading, it also appears that two principles are emerging: tamoxifen upregulates Her2, while herceptin upregulates ER. I think the key to long survival for triple positives is extended therapy which maintains a balance in the tension between these two opposing bc pathways. Again, I am not any type of medical professional, just what I consider to be a well read patient, and these are my opinions and no more than that. Hopeful