Crossing the street, eyes closed

Allow me to pose a question.  When you cross a street, do you look both ways?  Do you check for a bicycle, car or truck, which might strike you down?  Do you check every time you cross the street?  Do you ever, consciously, decide not to check, and just bolt across assuming you will not be struck dead?  Me, I am a little compulsive, so I look twice, both ways, every time I cross the street. How about you?

Dumb question, right?   Who would deliberately ignore the threat of a mass of hurtling steel?  We all look, always.  Self-Preservation 101.  Nonetheless, things are not so simple.  Perhaps there are times when we would rather trust luck, then scrutinize the road.

Consider the IBIS-II Trial, published in December (The Lancet, 12/12/2013).  This large study attempted to determine if the estrogen suppressing drug anastrozole, can reduce breast cancer occurrence in women at high risk of getting the disease.  With great enterprise and difficulty, 2864 women were recruited, educated, consented and randomized to receive either the study drug or a sugar pill (placebo) for five years.  Their physicians followed them frequently.  Neither the doctors treating these patient, nor the patients themselves, knew which pill they were taking. 

The great news is that anastrozole decreases the rate of new breast cancers by 50%.  Thus, we have another valuable tool to prevent this dread malignancy.

The bizarre news?  32% of patients who were taking the study drug, anastrozole, stopped taking the medicine during the study.  Even more remarkable was this; complaining of side effects such as nausea, fatigue, bone pain, and hot flashes, 28% of the women taking the placebo, also stopped taking those pills. That is right … hundreds of women complained the sugar pill was making them sick.  In addition, women in both groups dropped out of the study in the middle, stating that even though they had signed up, after thinking about it, they refused to take the medicine.

I guess I am naïve, because this kind of makes my head spin.  You have been told that you have a marked increased risk of breast cancer, because, for example, your sister or mother had breast cancer, you come from a family with multiple cancers or you have highly dense breasts, (many of these women had more than four (4) times the average risk for breast cancer); yet you will not try and protect yourself.  In addition, while I can understand that someone taking the anastrozole might experience enough complications to preclude continuing, what about the “side effects” in the sugar pill group?

One concludes that a combination of anxiety and mistrust regarding medication side effects, mixed with normal day-to-day aches, lead these women to drop out.  I hope that many of the side effects went away when they stopped the placebo, but we really do not know.  Given that the poor compliance rate was similar in both groups, do we even know there were any “real” side effects of the study drug?

So, what might we conclude about people and research from IBIS-II?   First, it is extremely difficult to carry out high quality clinical scientific research on an animal as complex as a human being.  It is hard to get good data when the subjects keep mixing us up.  Second, it shows the emotional and supra-tentorial component of human physiology.  It also reminds us there is a significant need for improved medical education of patients and the general community.  Finally, there continues to be a glaring gap in the trust between patients and organized medicine, which no doubt interferes with good health decisions.

We all deviate from the best health decisions for many reasons, and we harbor the vague concept that we “know” better.  Still, it would seem we have a long way to go when women who have drastically elevated risks of breast cancer are willing to cross life’s street, even occasionally, ignoring the malignant machine bearing down on them.   I would suggest that when we know there is great risk, it is worth trying to prevent catastrophe.  Me, I will continue to look when I cross … both ways.


  • Jill Aravena
    This is ironic. Today is my 36 birthday. Exactly one year since I've been on tamoxifen. I remember sitting there saying I wasn't convinced I needed this medication. I didn't have breast cancer! I knew I was high risk because of my ADH and my family history but I told myself over and over I didn't have cancer so why do this? It wasn't until you said that exact scenario that made me think. That's not saying it has been easy. Because it's not! But I do know I have trust in you and my breast specialist. And one thing for sure is I will always have more hope than fear.
  • Mary
    You pose an interesting problem. My experience with clinical trials is this - I took a drug that later was found to increase my cancer risk for a condition that it was later found I did NOT have.
  • Sandra
    Why would you equate taking an experimental drug---with, at the time of the study, entirely unknown risks and benefits---with looking both ways before you cross the street? The women who dropped out of the study apparently did not have any understanding that the drug might reduce their risk of recurrence because that would not have been known until AFTER the study concluded, right?
  • This is fascinating. It is the first time I've heard of a "negative" placebo effect!
  • I am taking Anastrozole -- and I look both ways and also check for dummies running the red lights! I'm not experiencing any side effects and have been on this medication for over 3 years. Yes, more Hope than Fear as Jill says in the post above.
  • Liz
    Hmm in Cambodia you walk slowly into the street, do not make eye contact (because if you do then you have to give way) and everything in the street from elephants to trucks goes around you. Chaos in slow motion. LOL What is the ABSOLUTE risk reduction for these women? 50% of what risk? I opted of out tamoxifen for one of my breast cancers cancers due to the fact that the absolute risk reduction of recurrence would be changes 2-6% (based on oncotype dx score of 2). Wasn't worth it to me as I already know what happened (which I wasn't warned about) when I was given depo luepron to try to shrink fibroids (they didn't shrink but we managed to permanently shut of my ovaries doing that). My brain needs estrogen (as there a range of those sensitive to its effects I must be on the high end) also interesting study of older women in a nursing home classified as senile - they were given estrogen replacement. 1/3 no longer classified as that, 1/3 showed some improvement, 1.3 no change (older study). But yes the power of suggestion does affect people…even when logic says it shouldn't. MD"s probably should have placebo pills to hand out when needed too LOL
    • Jill Aravena
      Dr. Salwitz explained my risk is 1 in 3. And by the end of the tamoxifen it should be 1 in 12. I have struggled daily and have been told by two other doctors that tamoxifen is very toxic and I shouldn't be on it. I have questioned myself everyday for exactly one year (today) if I'm doing the right thing?! I can only hope. Pray. And take confidence in my doctor that his experience and knowledge is far greater than mine.
  • Alyce
    I took Tamoxifen from 1992 until 2003. I was cancer free during this entire period and the only problems I experienced were an occasional hot flash. In 2012, I had a recurrence in 2012 and post-mastectomy, I began taking (and am still taking) Anastrazole. Thank God for the women who go through the clinical trials because somebody had to test these drugs before they gave them to the rest of us.
  • D Someya Reed
    One thing I’ve always found bothersome about clinical trials (at least the interpretation of the results) is the emphasis (and press) given to those control participants who develop negative effects attributed to psychological means with or without physical manifestations. Yet, so little is said or done to discover the number of non-control participants who did not have physiological changes measurable and attributable to the actions of the experimental drug and either did not get cancer or improved if they already had it. Most answers I’ve ever gotten have boiled down to variations of “We’re not looking for that.” I’ve always found that answer odd too because you’d think you’d want to know if the drug affects each participant in either the same or a predictable manner/method. However, that does add cost. Why is it not considered equally likely that if a person can mentally develop and physically manifest negative side-effects on a placebo that others could conceivably stimulate natural body/mind defense or offense mechanisms while taking the experimental drug without showing any measurable, physiological effects known to be associated with the use of the experimental drug? I rarely see any “equal time” given to this possibility; rather, any “good outcome” is automatically attributed to the effect of the drug. Perhaps this could add another explanation as to why some drugs are found later not to be as good (or far worse) than originally thought? Participants leave clinical trials for many reasons including, I believe, a heightened sense of intuitiveness to the commonly overlooked body language cues of bias, expectation and reaction (to participants) by those conducting the clinical trial whether it be a blind one or not. Every day in every situation, we “telegraph” a lot of silent information through visual cues, vocal tones, etc without ever realizing it. There is so much about our mind/body relationship of which we haven’t a clue. To criticize, in some cases and intentionally or not, or to identify, even as a group, those who manifested by any means negative or unexpected side effects does little to encourage others to sign up for later clinical trials.
  • D Someya Reed
    I should add to paragraph #1 above that I've also been told that determining how a drug affects people is part of the reason for the clinical trial. That may be somewhat true in a specific sense but I've always thought the primary reason for a clinical trial was to determine efficacy. If you have no clue as to how a drug is intended to physically affect a participant then I think you have no business giving it whether the participant agreed or not. You may as well say, 'I don't know what this is but try it and let's see if it works.'
  • My mother had breast cancer and refused chemotherapy, and only did radiation and had a lumpectomy. She was NED for almost 8 years while taking tamoxifen. She was asked to joint a drug study for the next generation drug to tamoxifen. Shortly after participating in the study she was diagnosed with metastatic breast cancer. She was informed that she had been taking the placebo in the study. I am thankful to my mother for taking the risk and joining the study, even though there was NED. I believe the tamoxifen helped her live the 10 years that she did live. I am also a little sad that she did not get the real drug and I could have had her with me a little longer.

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