HER2 Support Group Forums - View Single Post - her2 breast cancer cured (when transplanted in mice) using triple targetted therapy

Lani · 05-02-2007, 11:38 PM

One of the big differences between that abstract and this article is that in the study cited in the ASCO abstract they used not only MCF7 cells transfected with her2 (an artificial construct which may not have any similarity to any naturally occuring tumor) but also BT474
a tumor which naturally occured in the poor person whose cell line was propagated and perpetuated which is her amplified (eg FISH+) and ER+. This human breast cancer cell line was implanted into the rodent,so...

This is as close as it gets to simulating her2+ER+ breast cancer as it occurs in humans.

Estrogen depletion ie, AIs were studied --in the abstract I believe only tamoxifen was studied, which represents a SERM, which blocks the estrogen receptor rather than depleting estrogen.

For all of those (like Jean) wondering what is the best AI, or whether STS and'or 17OH-HSD should also be blocked (aromatase is only one of three enzymes responsible for the formation of estrogen and similar compounds
not only in body fat, muscle and adrenal gland, but also within the breast cancer cells themselves), and worrying about using creams with parabens and other estrogen-like compounds, I thought the following sentence was particularly helpful:

All BT474 tumors treated with pertuzumab, trastuzumab, and gefitinib disappeared rapidly, regardless of endocrine therapy, and no tumor progression was observed for 232 days.

It is the same team of investigators who presented (abstract) and published
(today's article) both. It represents continued work by the lab on the same issue over the years...they have improved the meaningfulness of their study but adding the more representative cancer cell line (BT474), trying to gauge the import of estrogen depletion as well as estrogen receptor blockade (perhaps even addressing ER degradation if I remember correctly and Fulvestrant was addressed--but that might have been another article I read today), and determining that even without removing estrogen or preventing it from having its usual proliferation-inducing effect these three targetted agents sufficed to "cure" this subset of breast cancer which represents about 10% of breast cancers

Genentech makes two of the three drugs and also makes Tarceva, which works similarly to Iressa, but which, unlike Iressa is FDA approved (for another purpose). Let's hope Genentech hops on this bandwagon!

I went again with my friend to this year's Annual Stockholders Meeting (I am not a stockholder). They reported good progress with pertuzumab--
for the passive among us, let's hope and pray...for the activists among us, let's try to use our energies to help push this progress forward!

05-02-2007, 11:38 PM	#11
Lani Senior Member Join Date: Mar 2006 Posts: 4,783	Joe (and all) One of the big differences between that abstract and this article is that in the study cited in the ASCO abstract they used not only MCF7 cells transfected with her2 (an artificial construct which may not have any similarity to any naturally occuring tumor) but also BT474 a tumor which naturally occured in the poor person whose cell line was propagated and perpetuated which is her amplified (eg FISH+) and ER+. This human breast cancer cell line was implanted into the rodent,so... This is as close as it gets to simulating her2+ER+ breast cancer as it occurs in humans. Estrogen depletion ie, AIs were studied --in the abstract I believe only tamoxifen was studied, which represents a SERM, which blocks the estrogen receptor rather than depleting estrogen. For all of those (like Jean) wondering what is the best AI, or whether STS and'or 17OH-HSD should also be blocked (aromatase is only one of three enzymes responsible for the formation of estrogen and similar compounds not only in body fat, muscle and adrenal gland, but also within the breast cancer cells themselves), and worrying about using creams with parabens and other estrogen-like compounds, I thought the following sentence was particularly helpful: All BT474 tumors treated with pertuzumab, trastuzumab, and gefitinib disappeared rapidly, regardless of endocrine therapy, and no tumor progression was observed for 232 days. It is the same team of investigators who presented (abstract) and published (today's article) both. It represents continued work by the lab on the same issue over the years...they have improved the meaningfulness of their study but adding the more representative cancer cell line (BT474), trying to gauge the import of estrogen depletion as well as estrogen receptor blockade (perhaps even addressing ER degradation if I remember correctly and Fulvestrant was addressed--but that might have been another article I read today), and determining that even without removing estrogen or preventing it from having its usual proliferation-inducing effect these three targetted agents sufficed to "cure" this subset of breast cancer which represents about 10% of breast cancers Genentech makes two of the three drugs and also makes Tarceva, which works similarly to Iressa, but which, unlike Iressa is FDA approved (for another purpose). Let's hope Genentech hops on this bandwagon! I went again with my friend to this year's Annual Stockholders Meeting (I am not a stockholder). They reported good progress with pertuzumab-- for the passive among us, let's hope and pray...for the activists among us, let's try to use our energies to help push this progress forward!