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Dec 27, 2018 09:24PM
Dec 27, 2018 11:54PM
Hope the golf was great!!!
You are spot on - there is a fair bit of detail (this and a few more ) if you go looking under "hypothesis" but broadly AIs fail because:
- aromatase independent oestrogen pathway
- oestrogen independent ER function
- ER independent growth signalling
Anastrazole and Letrozole are non steroidal aromatase inhibitors.
Letrozole is more potent then Anastrazole at 2.5mg per day versus 1mg - although I would venture the side effect profile is higher.
Exemestane is a steroidal aromatase inhibitor that irreversably binds aromatase. Aka suicide inhition.
The steroidal component has been associated with severe mood swings etc.
Fulvestrant is a selective receptor degrader - acts on ER.
Interestingly some works suggests
Depending on the reason why the AI fail in a specific patient it is totally reasonable to think you may be able to use other hormonal therapies in combos. Add to this tumour heterogeineity - meaning it may fail on only part of your tumour mass - and the picture gets cloudy.
What is coming out loud and clear is that smaller doses in multiple combos potentially changed over time before ??? and this is where i go out on a limb - progression occurs might be the way of the future. The aim being to minimize side effects and maximize therapeutic impact.
This is not rocket science - odd its the way we treat pain - multimodal, hypertension and even diabetes...
Some of this was not done until now because really there just werent enough options on the market.
Marian - Love your messages - so good to see you getting out. Maybe I will see snow nextChristmas.
Snow to all,
8/5/2016, DCIS/IDC, Left, 4cm, Stage IIB, Grade 2, 1/13 nodes, ER+/PR+, HER2-
8/11/2016 Lymph node removal: Underarm/Axillary; Mastectomy: Left; Prophylactic ovary removal
9/11/2016 AC + T (Taxol)
2/20/2017 External: Lymph nodes, Chest wall