Lisey that's how I remember it - a whole conversation. When I originally read it before I was posting on this thread, I thought about clarifying that Hope was correct, but it was years old at that point so I didn't bring it up.

Thanks for sharing your good news shepkitty - you're one of my role models of how to live if the news is not what I want to hear.

Some of you who have known me for awhile know that I live in a place where excellent medical care is is simply not available. I never say where because I have paranoia about people I know IRL stumbling onto my posts and recognizing me by my location. No one in my life knows most of the stuff I share here. But suffice to say it is very different from the rest of the country. Every single step of the way since my dx I have had to deal with the same kind of incompetence, misunderstandings and mistakes that I am dealing with now. If I don't double check everything everyone else does it's guaranteed something will be missed and I'm afraid these people are going to kill me eventually.

That is still going on right now so I had to just go get the x-rays and sports medicine doc's report and read it for myself to see what the hell he really said. I wanted to do that with my oncologist in the room but I couldn't wait anymore because they scheduled me for the MRI in 3 hours, after I told them I wasn't taking any more steps until someone explained this stuff to me. Man it was scary opening that envelope, but there is NOTHING in this report about erosive changes of the clavicle!! It says "cortical hypertrophy of the clavicle (the overgrowth he mentioned to me), minimal osteoarthritis of the AC joint, and right biceps tendinitis. The MRI is truly to rule out metastisis because of my history, not a strong suspicion that it is definitely cancer.

It appears sports medicine guy told me the truth, but made the error when writing the MRI order. I have been trying to get that cleared up since Monday morning, not a single call has been returned. Eases my mind quite a bit, although I know there is still a chance it is cancer because we all have that chance. But I'm able to go in there tonight hoping for the best, and mean it.

Sorry for hijacking this thread with my personal problems but since I started it here I didn't want to have to answer a bunch of the same questions on a new thread. I keep saying this, but what would I do without the ladies of BCO?

that is good to know, solfeo. Good luck with mri.

Lisey ~ Thank you

This is a report from October 2015 that would support the idea that CYP2D6 allele status makes no difference in Tamoxifen effectiveness. Information was taken from several sources, which are all cited. This also confirms my thoughts as to using our tests for guidance and not as an absolute, final indicator of how our meds will work for us.

Tamoxifen Metabolism and CYP2D6 Overview of the Action of CYP2D6

"In an attempt to settle this issue, investigators assessed data from the large, prospective Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (BIG) 1-98 trials that, in combination, had randomized more than 9000 patients to tamoxifen or to anastrozole or letrozole, respectively.^{[10, 11] "}

"In both assessments, CYP2D6 allele status had no effect on any outcomes, including disease recurrence, distant recurrence, and overall survival.^{[12, 13]} In addition, because it was thought that the presence of hot flashes might be an indicator of metabolic activity of tamoxifen, BIG 1-98 investigators also looked at whether the presence or absence of hot flashes might correlate with CYP2D6 allele status. Again, no difference was seen between the groups.^{[13] "}

"some have suggested that all of the current data may be suspect because of the poor understanding of the metabolism of tamoxifen and endoxifen within the cytochrome P450 pathway.^[14]"

"Ongoing studies of patients with metastatic breast cancer that are incorporating genetic testing will add more information to the debate,^[16] but it is unclear whether they will fully resolve the question of how and whether CYP2D6 allele status influences outcomes from tamoxifen therapy given in the adjuvant setting."

We need more research! There is absolutely no reason for any of us to go blindly into treatments; Tamoxifen, AI's, chemo's........ The tools are all there, but there isn't a proper manual to go along with 'em

Lisey ~ I go to follow up with my MO and Oncology-Neurologist tomorrow. I have a LIST of questions. The Onc-Neuro likes talking the sciency stuff.......anything I should ask?

Labelle ~ Hey you! How's Tubby Kitty? Yikes, your Tamoxifen SE's were awful. I was just fat, sweaty and grumpy. I lost 10lbs within a few weeks of switching to Femara. My hot flashes got much better too. Some say I am still grumpy..........

Solfeo ~ Yay! Told ya the MRI was no big woof. I have never had the phrase "role model" applied to me in a positive way - thank you sweetie (hush Sas, let me have my moment!)

As for your chitty medical services......

The American Cancer Society offers transportation, including airfare, for treatment in or out of your area. They also have very nice hotel accommodations that are free to stay at while being treated. They will pay for someone to accompany/stay with you as well.

Find Support & Treatment Topics

American Cancer Society Hope Lodge.

Here is the link to The National Cancer Institute. Use their guide to find an NCI designated cancer center

There are also other links for resources on the NCI site.

Check with your insurance company as to which centers they will cover. If you do not already have one, request a Case Manager via your insurance company to help you navigate your treatment processes. The Case Manager is an RN who can advise medical situations, refer to local support sources and help to push through necessary pre-approvals.

My center here in SC is NCI Designated. Should something happen to my MO or if I need treatment someplace else I have two other hospitals on my "standby" list.

Try for Charleston. IMO they are the best. The Hope Lodge is not even a block away and is in a beautifully renovated old Southern home. And I will come visit you

Bestbird and Sas had links with a ton of info on available resources. I'll post them here or I'm sure Sas will.

Shepkitty - you certainly are a role model! I don't care what sassy says LOL

The Big 1-98 study has been criticized by some experts for using breast tumor tissue rather than germline DNA (from the blood) to determine CYP2D6 status. The results can be different a good percentage of the time (I want to say around 20% of the time, but that is from memory so don't quote me). There were also some other inconsistencies noted at the link I posted yesterday upthread.

Besides genetics the other obvious issue is tamoxifen resistance. You can have enough of every metabolite you need and the cancer just finds a way around it. That is a possibility with any treatment but may be more prevalent with tamoxifen. I say "may" because it's just something I picked up from reading and I can't cite a source. If anyone knows otherwise please correct me. This is why I don't understand this push to extend tamoxifen therapy to 10 years. The longer you take it the more likely the cancer is to become resistant. If I was more than 5 years away from menopause, it would be my choice to switch to an AI+OS or oophorectomy after the first five years on tam. My original plan was 2 years on tamoxifen then switching to AI alone (assuming my menopause was complete), although I was given the choice to stay on tam as long as I wanted if I tolerated it well. My reasoning was that the more serious side effects become more likely after 2 years.

MRI went well, although there were still some miscommunications between what sports medicine doc and MO had ordered. I tried straightening it out but it was 6pm, the docs offices were closed, and I finally just had to say screw it and hope for the best. I have the images, but heck if I can tell if anything looks abnormal. Both doctors should be getting the reports at the same time, and neither has called so I guess the results are not posted yet.

NO METS!!!!!!!!!!!!!!!!!!!!!

I have five other diagnoses that might be disheartening on any other day, but today it's like somebody gave me a big bag of money!

Awesome Solfeo!!! So happy for you!!!

solfeo YaY

I've edited this post to reflect your last post, which somehow i didn't see first. That is disappointing but I'm sure you are right. .. they just would not have missed mets. Hope you get definate and good news soon.

I finally had enough of this BS and broke down and had a few cocktails to de-stress last night, which I don't normally do. Then the freaking MO called while I'm sitting there buzzing, so I couldn't answer it. Would you believe that this kind of stuff happens in almost every medical situation I find myself in? It's like living in a third world country where I live.

They only looked at the shoulder joint because the MA only put down "pain in shoulder joint" as the indication for the MRI. Hypertrophy of the clavicle was nowhere on the order. I tried to prevent this from happening but it was still not straightened out when I got there, and as I said, it was after normal business hours and there was nothing I could do about it. How visible the relevant area is in a shoulder MRI, I don't know, but there needs to be some commentary by the radiologist on the specific issue of clavicular hypertrophy.

I have sent one last clarifying email to my doctor, with strict instructions that he should read it personally to avoid further miscommunication. Hopefully this will get cleared up today before the weekend.

Good luck, Solfeo, hope you get a definitive answer from your doctor today.

solfeo, have you seen the sports guy now and are you completely reassured?

Ugh on all the shoulder issues, Solfeo. Hope the PT works wonders.

Hi Lisey. I don't want to reply in depth until I refresh my memory on ultrarapid metabolizers. It means you have more than 2 copies of the CYP2D6 allele. You're a mutant! LOL! Do they list them and say how many? That might make a difference.There have been people with over 10 alleles described in the literature, but I don't know how common the larger numbers are. I'm guessing the higher it gets the more difficult it would be to maintain the desired endoxifen level, but you might be OK if you only have 3 because tamoxifen has a long half life. I just can't remember without doing some reading so I'll have to write more later.

I don't think the correlation between side effects and effectiveness/endoxifen is clear cut. I'm still not having that hard of a time even after over a month on the doubled dose. Studies, as you know, have had conflicting results, but it does take tamoxifen a couple of months to build up in the system and side effects can be delayed. Regarding codeine, it could be that you have another gene that makes you less susceptible to its effects.

Quickly, here's what YouScript says about ultrarapid metabolizers. The possibility of better outcomes is mentioned, which is good, but so is increased risk of adverse effects. It's only the truly dangerous ones that I would worry about but you can always adjust your dose based on your endoxifen tests. We can dig deeper into your specific situation when you get the report. I'm off to the cardiologist to find out if I need heart meds, which is going to be another CYP2D6/tamoxifen ordeal. Hope she's going to be open to the information.

Effects

Summary: A correlation between CYP2D6 polymorphism and tamoxifen levels has been established. Tamoxifen is a pro-drug metabolized by CYP2D6 to endoxifen, which is 30-100 fold more potent.

I. Pharmacokinetic Studies

N/A

II. Pharmacodynamics/ Clinical Outcomes

Although no published literature was identified specifically for CYP2D6 ultra rapid metabolizers (UM) and tamoxifen, a case study concluded that CYP2D6 UMs may have improved outcomes, but increased risk of adverse effects when administered tamoxifen.¹

A clinical study found that CYP2D6 UMs were more likely to develop two or more side effects to tamoxifen and had an overall increase in the median number of side effects compared to CYP2D6 IM/NM and PM patients.² This may be due to increased plasma concentrations of the more potent endoxifen metabolite.

Management

The Dutch Pharmacogenetics Working Group makes no therapeutic dose recommendation.³

Consider increased monitoring for tamoxifen adverse effects such as thromboembolism, irregular vaginal bleeding and hot flashes and adjust therapy accordingly.

The National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) do not recommend CYP2D6 testing as a tool to determine the optimal adjuvant endocrine strategy.^4,5