Half of breast cancer patients treated with antihormonals are noncompliant ie, do not

[Hopeful]

I am still trying to reconcile the doctor's reccommended "vacation" with the compliance issue as described in the article and some earlier posts. I looked up the FDA approved inserts for the most common AI's, Femara (Letrozole) and Arimidex (Anastrazole). Here is what it says about how long the drug is active in the body when you cease taking it:

Letrozole’s terminal elimination half-life is about 2 days and steady-state plasma concentration after daily 2.5 mg dosing is reached in 2-6 weeks.

The reccomended daily dose, ARIMIDEX 1 mg, reduced estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing. Suppression of serum estradiol was maintained for up to 6 days after cessation of daily dosing with ARIMIDEX 1 mg.

So, if you are on a month's "vacation," you are unprotected for rougly 24 days out of 30. If you take enough "vacations," how does that impact the statistical results you will see?

The fact of the matter is, no one knows what the truly optimum duration of therapy with these agents is. My onc said to me that 5 years of treatment is an arbitrary number based on the arbitrary number of 5 years used in trials. When issues arose about the potential for exended therapy, he said to me, the drug manufacturers were probably saying to themselves, "Dang, we should have gone for 10 years from the start!"

These are pills, not magic bullets. They are efficacious and toxic in about half the patients who take them, and just toxic in the other half. It is not unreasonable to balance QOL against the particular risk you are managing in deciding how long to take them.

Hopeful

[AlaskaAngel]

Also, in 2002 when I was diagnosed, AI's were still being tested for metastatic bc and were not given for adjuvant therapy, so they still have a relatively short history of use in terms of what the effects actually are for long-term use. Adjuvant use is the group with the longest likely duration of use.

We ARE the test group. If they don't hear much from us, they aren't going to see or focus much on any problems with these drugs -- any more than they have about the issues of chemo brain or sexuality. As long as we take the attitude that we "have to suffer" to stay alive, it isn't likely that anyone will do much about it.

For example, if the intention of using these drugs is the effect on aromatase, then what is bringing about the joint pain? Is there aromatase in our joints? And if there is joint pain where there is no aromatase to inhibit, what ELSE does the drug do that is not sensed through the nervous system but that may not be beneficial long-term? Is bone loss a side effect, or a primary effect? Are there other "side effects" that are unintended and that long-term are not beneficial that genuinely should be considered along with QOL in making a rational decision about whether to discontinue the drug or take it long-term?

A.A.

[Carol.hope]

I have been taking natural aromatase inhibitors - first, Indol3 carbinol and then DIM, advised by my naturopath. This is the ingredient in broccoli that is helpful against cancer. You might try that during your "vacation" from AI. I had my estrogen levels checked through a test that showed that all the hormones were being processed into "good" estrogen, and not the "bad" estrogen. Also my bone density is getting better, not worse.

I don't think most regular oncologists know about these approaches, but some do. Here's a site I just found, which has links to more information: http://www.dimfaq.com/. I recommend getting an MD or ND's help, not just giving up your AI.

- Carol

[CoolBreeze]

I've only been on tamoxifen 2 1/2 months, and I was pre-menopausal at diagnosis (51). I find it hard to believe the symptoms I am having are normal menopausal symptoms. I know many women who have been through menopause and they don't have continual deep bone aches, joint pain, and cramps. Many get hot flashes but mine are continual. Sleep disorders are common, of course, and I haven't slept for more than 2 hours since I started the drug. It only took two weeks on the drug before I got a vaginal infection. I always looked younger than my age, but now my skin is crepe-papering up.

I have been compliant with every medication I've taken in my life and do take my calcium and vitamin D faithfully - but I can totally see why people would not continue with this one, dangers or no. My quality of life has diminished greatly - frankly, I'd rather do chemo again than take this drug for five years. I have a 13 year old and lots of activities left to do with him.

I'm one of those people who sail through everything - chemo, never had a side effect of any med - and now this happened. I was very surprised - I hadn't even looked into the SEs of tamoxifen until a month down the road.

So many things I can't do anymore, and I could before. Stand for long periods, sit for long periods (back aches) - my hips hurt. I can't even wear heels. I love heels, I have 100 pair! Unless I know I won't be walking at all, they have to stay in my closet.

So, I completely understand non-compliance.

My onc has prescribed me percocet but for how long? I'm certain he's not going to give it to me for five years.

I'm just hoping something better comes along. I will continue to take it - for now. I can't promise anybody I can do this for five years.

[MJo]

I love this topic. I have a year to go on Femara and I want to stop now, but I won't. I had a 30 day vacation from the drug when my liver enzymes went haywire. I felt MUCH better. I asked the Onc if I could take Femara every other day. He and the Nurse Pract. strongly urged me to keep taking it every day. I hate this stuff. I told the onc that god/creator made women's bodies with estrogen and it isn't natural to get us down to 0. He said men do without estrogen. Something is not in synch with that reasoning! Duh! Finally I told him that I'm right on this one and he's wrong. I can see why women -- young and old -- are not compliant. In fact, I'm in a clinical trial with Femara, and the nurse told me many women in the trial have stopped coming back for their meds. Hah! Thanks for letting me B---h. I will continue to take the Femara, but under protest.

[CoolBreeze]

Wow, your doctor actually said "men do without it?"

I think I'd drop him like it's hot.

Women do without testosterone* too, does that mean that he shouldn't complain if he had to block his? He shouldn't complain if his muscles whither, if he can't get it up anymore, if he goes completely bald?

You know, I'm not even sure that guy has a medical license, if he doesn't know the basic differences between men and women.

My eyes are rolling in my head.

[TSund]

I am interested in this thread. I am very concerned about the suffering that women have while on these drugs. Ruth has only been on Armidex for a short time, (after a couple years on Tamoxifen, fortunately fairly non-eventful) and has already got such stiff knees that she gets discouraged. I read that some women totally stop their exercise regimes out of necessity, and there is weight gain associated with these drugs also. There are reports that some women have permanent joint damage from the AI's, and there is of course the bone loss issue also. To read something like these reports really brings it home.

http://www.askapatient.com/viewratin...&name=ARIMIDEX

I believe that Her2+ women might be more motivated to stay on these drugs, due to the fast growing nature of Her2 cancer, but it really seems like a catch-22.

My question is this: There is a proven cancer reoccurance rate reduction associated with a diligent exercise regime, and there is estrogen associated with fat cells as well. Isn't the risk factor affected negatively by these two items, possibly affecting the benefit of putting up with these drugs? Not to mention the osteoporosis factoring in.

By the way, Ruth takes DIM also. I believe that one of the things that DIM does for you is help the liver to process the excess estrogen out of the body.

I am wondering also about the dosage unknowns. Is the fear that a lowered dosage has a diminished affect or is that actually fear that a lowered dose could cause other unknown problems? I have long thought that meds should be adjusted by body weight just as chemo is. makes sense, but of course there is no stats to inform.

[Barbara2]

I have had 7+ years of Arimidex and will probably continue to take it. My onc said that some doctors are looking at possibly 15 year's use. Stiffness is an issue only when I first start to walk after sitting/lying, etc. Aches? Oh yes, but I also have fibromyalgia, so it's hard to know the source of the off/on discomfort. Age could be a factor, also.

The last time I saw my onc, I asked him if he would be continuing the Arimidex, if I was thin. (I'm about 30#s overweight.) He said yes.

I often wonder about the long term damage that may come from all of this. I've taken Zometa for bone loss which I didn't have before taking Arimidex; another unwanted side effect.

It's a gamble to take it, and not take it. I've chosen to stick with my current treatment and pray that it is the best choice, but know it doesn't come without risks.

[Hopeful]

Supplementary editorial provided by OncologySTAT

TAKE-HOME MESSAGE

Less than half of breast cancer patients who start adjuvant hormonal therapy remain adherent for the full duration of treatment.

EXPERT COMMENTARY

Lee Schwartzberg, MD, Editor-in-Chief

Increasing use of oral therapies in oncology has appropriately focused attention on adherence with dosing over long periods of administration. There is rising concern that, due to cost, side effects, psychosocial issues, and other factors, patients may be compromising their health but not taking medications as prescribed. This study supports this assumption by demonstrating that fully half of patients prescribed hormone therapy for breast cancer are nonadherent over 5 years. Much more effort is necessary to improve provider-patient communication, as well as monitoring and adherence promotion, regarding oral agents. Reliable delivery of active therapy is as important as the actual development of new treatments in order to achieve optimal outcome.

STUDY IN CONTEXT


Adjuvant hormonal therapy with tamoxifen or an aromatase inhibitor (AI) for 5 years significantly reduces recurrence and mortality in women with hormone-sensitive breast cancer. Yet studies show that early discontinuation rates are high, and adherence rates are low, for this potentially life-saving regimen. Previous adherence studies were small and focused primarily on elderly patients. Hershman et al, using the database from Kaiser Permanente of Northern California, studied the problem in a large, diverse population that had equal access to health care and prescription drugs.

The database included more than 15,000 women who were diagnosed with hormone-receptor−positive stage I−III breast cancer between 1996 and 2007. From this cohort, the researchers identified 8769 eligible women who had filled at least one prescription for an AI (anastrozole, exemestane, or letrozole) or tamoxifen, or both, within 12 months of their diagnosis and before any recurrence. The diverse population included ethnic Asians (11%), Hispanics (7.2%), African Americans (5.6%), and whites (76.2%).

Over 4.5 years of follow-up, 2790 (32%) patients discontinued hormonal therapy. Of the 5979 patients who continued, 28% failed to adhere to the regimen (19% of the total). Thus, only 49% of patients were fully adherent for the entire 4.5 years. Rates of discontinuation and nonadherence were similar from year to year.

Significant predictors of early discontinuation included age <50 years and >65 years (vs age 50−65), lumpectomy (vs mastectomy), and more comorbidities. Factors associated with completion of therapy included Asian/Pacific Islander ethnicity, being married, earlier year of diagnosis, receipt of adjuvant chemotherapy or radiotherapy, and longer prescription refill interval.

Factors predicting nonadherence included African American race, lumpectomy, unknown tumor size, lymph node involvement, and more comorbidities. Predictors of full adherence were earlier year of diagnosis, being married, and longer prescription refill interval. Results for both early discontinuation and nonadherence were similar for patients taking tamoxifen or AIs. The authors suggested that shorter refill intervals may be linked to greater nonadherence because of the inconvenience of frequent refilling.

African American patients were more likely than white women to be nonadherent, but there was no difference in discontinuation rates between black and white women. Asian/Pacific Islander women were less likely than other racial/ethnic groups to discontinue therapy, but their nonadherence rates did not differ from those of other groups.

Multivariate analysis using a more refined age categorization showed that patients at the age extremes (<40 years and >75 years) were most likely to discontinue or be nonadherent to therapy, compared with patients age 50 to 65 years. The 202 patients younger than age 40 were the most noncompliant. They were 50% more likely to discontinue therapy and 40% more likely to be nonadherent (P < .001).

Previous studies have also shown low adherence among younger women, but, as the authors note, these findings have received little attention. Younger women with cancer may face greater barriers to adherence since they are less likely to have health insurance; they may have greater psychosocial and medical challenges, since they are more likely to have a delayed diagnosis and less likely to participate in clinical trials.

The greatest barrier to adherence for patients involves poor patient/physician communication upfront, reflected in the fact that 13% of patients were nonadherent from the first refill. The physician may fail to fully explain the benefits of hormonal therapy or prepare patients for adverse events. In this study, 4% of patients filled only one prescription, and the early discontinuation may be related to early treatment toxicities.

Further research is warranted to explore the association between nonadherence to hormonal therapy and breast-cancer–specific mortality. Interventions that help patients adhere to the full course of hormonal therapy are needed, especially for younger women.

Hopeful

[AlaskaAngel]

"Further research is warranted to explore the association between nonadherence to hormonal therapy and breast-cancer–specific mortality. Interventions that help patients adhere to the full course of hormonal therapy are needed, especially for younger women."

Well, I wonder if more patients would be willing to give it a serious go if researchers would start by sitting down every day and taking a dose themselves. Since it is a relatively "harmless" medication, a year or two of it shouldn't hurt a bit....

[Carol.hope]

Good idea, A.A.!
I am just reading a book called "The Myth of Alzheimer's" in which the MD did decide to take the meds he prescribed, and gave them up because of the side effects! They made very little difference for the patients' benefit anyway, and he offers them but lets the decision be the patient's.

Re AIs. I can't remember how big a benefit they are supposed to make. I think recently they've been tested against Tamoxifen. But what about their benefit compared to placebo? In Dr. Susan Love's Breast Book, 4th Edition (5th coming out soon), she says (page 309) refers to the test comparing letrozole (Femara) with placebo, after 5 years of tamoxifen. After 2 years, the letrozole group's survival rate was 98.9% and the placebo group's survival rate was 98.6%. I think this means that less than 1/2 of 1% of people taking the drug are benefitting from it.

Dr. Love says that sometimes the side-effects outweight the potential benefits. There's no way to know if you're in the less-than-1% benefitting, but you do know if you're in the group with unpleasant side effects. The choice is the patient's.

The same purpose - lowering amount of estradiol - is addressed with DIM, with no side effects in my case. A urine test can tell you if it's working.

In summary, why is the medical system taking the strong position that they need to make sure patients take the meds, when another option is to let the patient decide, especially when the likelihood of the drugs actually helping the patient is very small? Don't we deserve treatment that is patient-centered, rather than drugs-centered?

[Jean]

Interesting topic, but no answer is found.
First of all I have alway thought that the women who are dx. at a young age are faced with so many issues.
As most young women today work full time and also are raising their families. Difficult in any form let alone adding breast cancer to it and the med.

The older group of us who were post menapausal are facing side effects of thinning hair, joint pain, and all the other issues that come with the AI med.

Most important for me I changed my gyo to a women a while back and found that a female gyo was a major difference than any male gyo. They know first hand what giving birth feels like, what our body parts feel like etc. If you have a dr. that you cannot discuss the AI issues with forget it, all is lost before you begin to open your mouth.

We just do not have all the answers to these meds.
For me with an estrogen level of 90% I decided to deal with the negatives issues and try to alter as much as I can. I do find that swimming is a great way to exercise and get results, strange that I can do laps in the pool and come out and feel no joint pain or ache. The swimming is great for getting my joints and muscles in shape. Too bad I live in the East and close my pool in the fall and I just do not make it to the YMCA pool.
I just can't seem to find the time to get there on a regular schedule.

Oh, talking about finding the time another point to consider is I find in operating my company that no matter what time line I give I will always have a % of people who do not comply with reports when due and other items, etc. Maybe the same thing with taking the med. Just maybe there is a % of women who have intentions of taking them and darn it the day flys by and she forgets or is just to busy with family and jobs? Who knows, we do not have the answers. There are many reasons for not taking the meds. By choice, by accident, etc.

We are all adults and have to make life choices that work for us on a personal level. Some of the choices we have had to make since dx. are risky and dangerous.
But so is our dx. No easy way in and for sure no easy way out.

Of course we must tell our dr. what our side effects are and some dr. are better at addressing those issues.
But the issues remain these AI do cause strong side effects and it is different for each one of us.
Just like our breast cancer.

Great Thread Ladies.
For me I will take my chances with the AI

Best Wishes,
jean

[swimangel72]

Thank you all for your comments - I find this thread very interesting, especially since after two and a half years on Arimidex the SEs have forced me to ask my onc to let me stop. He said I could have a "vacation" - but he's ordering a PET scan for me (my first one) which will help him decide how to move forward. Today is my second day without Arimidex - and although my bones still hurt, I do feel more energetic and less hungy, yay! I'm hoping my PET scan is totally clear so I can convince my onc to let me have a permanent vacation from Arimidex. For me, the SEs have been cumulative - the first 6 months to a year I didn't notice much of anything - but after 18 months, I really started experiencing problems (achy joints - bad hip - muscle weakness - lack of energy - total lack of libido) I was one who sailed through menopause (early - age 50) - so all these new SEs make me feel as old as my 85 year old mother! I told my onc there's no way I can continue like this for another 2.5 years - he's a sensitive person and good communicator, so I appreciate this vacation.

Edited to add: Hi Jean - we posted at the same time! I agree that swimming really is helpful - but these days, I told my onc it's not helping me anymore. My muscles and joints hurt in the pool and after I swim - nowadays I have a new pain in my chest close to my collar bone. I'm hoping it's due to Arimidex affecting an area I use alot in the pool. I have been trying to increase my speed and distance, but still poop-out after half-a-mile - in my old pre-BC days, I could swim a mile in 42 minutes, now I can only do half that.

[TSund]

Kathy's post about her swimming being limited above brings back the issue of a) excercize being a proven benefit for bc, with an added benefit for er+ cancers! and b) better statistics for thin women than for overweight women and the weight gain associated with the AI's. Ruth has had a devil of a time keeping weight off ever since chemo/tamoxifen/arimidex. (she started the arimidex a couple months ago)

I wish I knew how these factors work into the equation and the "survival benefit" for taking arimidex, femara, etc.

[v-ness]

i must confess, i have just become non-compliant after a mere 3 months my misery from tamoxifen is so severe. i only just stopped on tuesday and told my oncologist so on thursday when i went in for my herceptin appointment. i told him i would rather have puked my guts out for 3 months of chemo than deal with the havoc tamoxifen wreaks on my life. it wasn't so bad at first. the joint pain (knees) i can live with. just need to make sure that when i squat i have something nearby to grab onto to help get up, or get enough bounce to catapult myself upward. but the hot flashes and night sweats? unimaginable. chemo launched me into chemopause (i'd had a partial hysterectomy 8 months before cancer diagnosis but i know i was still perimenopausal despite lack of a period for lack of a uterus). i got hot flashes from it, but managed them pretty well with neurontin. but neurontin is nothing against tamoxifen. i don't know if the summer heat and humidity has increased the hot flashes/night sweats, but they have certainly intensified in the last month. i look like i've been doused with a hose. my face is beaded with pearls of sweat and it literally pours off my face, drips onto my chest. my arms and legs even sweat, something i only ever had happen when working hard on a humid day. any of you with these same severe symptoms know the drill. while on tamoxifen it happened literally dozens of times a day/night. i get that warning aura too, so i have a minute's notice that it's coming. it got so that my sleep was disrupted continually and i could barely get up for work in the morning.

how the hell did they put a man on the moon and cure male erectile dysfunction, and they can't do anything to curb hot flashes?

i am beside myself. i am something like 95% ER positive so i need this CRAP. i asked the onco the other day what my other options were and to my disbelief he said none. they can try me on effexor or black cohosh. has anyone had any luck on either of those? i am loathe to start taking the evil drug again. on my little hiatus the number of hot flashes i've had has at least halved.

what is the ER tx someone mentioned above?

me, i am heavily considering having my lone ovary out. i have an appt with my gyno on 8/9 about it. before it was just out of fear of cancer spread (and i've also had pain in my remaining ovary anyway). now i wonder if i got it out, would i then be post-menopausal and therefore have other drug options? or is it just more of the same living hell?

even as i write this i've had to throw off the sheet and turn on the fan, wipe my brow with my ever-constant bedside rag. and that's with the AC on full blast.

my cat Big thinks i'm awful tasty. every morning i wake to him licking the salt off my body. at least someone is enjoying this.

valerie

p.s. i've been taking evening primrose. doesn't help one bit.

[caya]

Valerie,

I have been on Effexor XR - 75 mg. 1/day for 3 years now, started about one month after starting Tamoxifen - the hot flashes were like you - totally unbearable... so my onc. suggested the Effexor, and it literally changed my life - good for the hot flashes, also helped the mood swings, anxiety etc. I have told my onc. I am never going off it, he just chuckles when I say that.
I started Femara on Jan. 1, 2010 (blood work confirmed I was post menopausal at age 51) - still taking the Effexor.
I have read that going off Effexor can be difficult, but quite frankly I will worry about that if that day ever comes - it works too well for me to ever consider going off it, at least while I am on AIs. I am 90%ER+/50%PR+, so I also must take this stuff.

JMHO.

all the best,
caya

[Becky]

Believe it or not, I have never once missed taking my Tamoxifen (devil drug) or Arimidex. Not once. Not even the one night in the Bahamas when my sister and me were so drunk I fell on the dance floor. I figure its my responsibility and duty to my family (although I probably could have just skipped it that one night in the Bahamas as it probably didn't do any good)

There are some things ya just gotta do...

[v-ness]

yes, but there's no reason to just grin and bear it if there is some way to make it bearable. if that means going on effexor if it can possibly relieve the symptoms, then it's worth a try. thanks, caya, for giving me some hope. i'm not a wuss, i've been through plenty of hell in my life (face first through a windshield in '89 for instance), and stopping the tamoxifen wasn't something i chose lightly. in fact, it's scary. i'm sure it's worse for some than it is others. i will resume it with effexor this coming week and hope for the best. it's pretty funny, once upon a time i went running in Death Valley when it was 100 degrees out and was just fine with that. but this heat from within makes Death Valley seem like the lesser of the two evils. i'm so glad you had success with effexor, caya. keep your fingers crossed for me! valerie

[CoolBreeze]

Becky, good for you on not taking it But, I have to say, I have a responsibility to my family too and if I hurt so bad I can't move I'm not living up to that responsibly either.

You have to really balance your quality of life with the possibility of recurrence and that's a pretty hard choice to make.

I'm still taking tamoxifen but only because I have pain control. There will come a day when he says "no more pain meds" and then I may have to reconsider taking it. I don't *want* to stop but my quality of life is not good at all. I'm on my third month and I have heard that some people adjust so I hope end up being one but so far, not good.

Even with percocet I have problems doing things. Today we went to a museum with the family, and just in two hours I was in some pretty bad pain, had to sit at the end, and wanted to sleep when I got home. I'm only 52 and was perfectly healthy before this. I could walk all day and never feel tired. Today, my back, my hips, my thighs, my knees just ached. Before, I looked and felt ten years younger. I didn't understand why people my age complained of aches and pains - I never had any. That's changed, with a vengeance.

I work in a school and go back to work in one week - haven't worked since I started tamox. I'm just not sure how I am going to be able to manage, getting up at 5:00 a.m. especially in the winter when it's cold and dark.

I don't want cancer again but also want to live my life. I feel like I'm on a teeter-totter.

That brings me to Terri's question about her wife and exercise. I had always planned to exercise as soon as my expander was out and I was healed. I have always been thin and so never got into the exercise routine. I have always been very healthy even without it, and even though I never did formal excercise, I walked places and took stairs rather than elevators, etc. I moved. But, after cancer, I feel like I should keep my body at its optimum and I thought I'd sign up for yoga or something gentle. I have not had weight gain from the drug but of course, it's important to exercise. I always knew that but ignored it.

I cannot even imagine it now since tamox, I hurt so much.

I am still going to try it when my surgery is done. Because, who knows, maybe it will help. Since the reason we have the joint pain is that our cartiledge needs estrogen and that's gone, and we lose that padding between our bones, then it seems logical that it is important to strengthen your muscles to take some of the pressure off your joints But, it's very hard to get motivated when you can hardly move until your two percocet kick in.

The hot flashes are miserable but the pain is the worst part. I could do it all without that.

For those of us who have the extreme SEs, like me, I think it's important that we tell our doctors that it is not like menopause. Because, it isn't. Think of all the thousands of 60-70 year olds out there who have been through menopause and who still ride bikes, take classes and live full lives. I think physicians need to know how bad it is - and not that we are just "suddenly plunged into menopause" which is what I've heard in some articles.

[Monica]

My decision to stop taking tamoxifen was very difficult for me, and not one that I did easily. I am 95% ER+. However, the tamoxifen caused me to have MS relapses. I tried three times, and every time I would have problems. Not to mention, I had anxiety spells that I never have had in my life and to be honest freaked me out. It has been six years since I have been diagnosed, and keeping my fingers crossed, so far so good. There’s a very serious risk with the choice that I made, but I asked myself if I would punish myself if my cancer came back. I decided, no; for me, quality of life trumped a possible recurrence.
Best,
Monica