her2 and ER and PR status are age-related--triple positive bc occurs ~5 yrs earlier

[Hopeful]

Understanding their findings is compounded because the article was either written (or translated into) English by someone for whom English is not the native language.

The authors sought to expand on earlier work detailed in a paper (which was an easier read!) where they determined that the ER+/PR- HER2+ phenotype was age dependant and was strongly associated with middle age. That study was questioned because of the small numbers of patients involved, so they sought to do a larger study with more patients.

What they found in the study population was that triple positives (ER+/PR+/Her2+) are the only group where the likelihood of Her2 positivity declines with age, i.e., the older you are and ER+/PR+, the less likely you are to be Her2+. Other Her2+ partially hormone positive phenotypes (ER-/PR+ or ER+/PR-) showed a constant probability that was not age related.

They consider their work hypothesis generating and not conclusive. Their theory is that hormone positive, Her2+ bc in younger women is regulated more by endocrines than growth factor signaling, and that these tumors are more sensitive to endocrine maniputlation, and that menopausal tumors that are hormone positive and Her2+ are more endocrine independent and less responsive to endocrine therapy. The reasoning this is based upon is the higher levels of circulating estrongen in the bloodstream of pre-meno women. They stress that testing must be done to prove or disprove this theory. If this turns out to be accurate, I think it is also a statement about the difference between ER+ bc driven by estrogen and ER+ bc driven by aromatase, which seems trickier to control with estrogen manipulation in the Her2+ context.

The issue I have is how they define "young". I thought the "young" vs. "old" categories referred to pre and post menopause, but then they say, "In conclusion, our believe that HER-2 expression is estrogen driven in young women with an ER<SUP>+</SUP> breast cancers is reflected by a mean younger age of diagnosis (52.4 years) of ER<SUP>+</SUP>PR<SUP>+</SUP>HER-2<SUP>+</SUP> breast cancers, on average 5.4 years younger than lesions with another ER/PR/HER-2 receptor status (95% CI = 3.3–7.5; P < 0.0001)."

Again, my math skills aren't my strong suit, but I am guessing this means that the larger number of pre-meno triple positives offsets the much lower number of post-meno triple positives and thus brings down the mean age for the entire group to where it is lower than that of any other phenotype.

Hope this helps.

Hopeful