Tamoxifen for Non Invasive LCIS

Jenny,

I had ILC and LCIS. This is a very old study, but stays Tamoxifen reduces LCIS risk of developing invasive cancer by 56%:

http://www.ncbi.nlm.nih.gov/pubmed/9747868?dopt=Ab...

Georgie

Melissa,

Yes, determining the possible benefit of any treatment will depend on each person's risk factor of developing breast cancer. The statistics can be a crap shoot. I was told my neutropenia from sulfa is only experienced by 1 in 10,000 and that LE only occurs in 1-3% of women with sentinel node biopsies. But I still have LE. I was also told it is rare for calcifications to be LCIS and for me they were. So I look at statistics but know they may not apply to me.

Jenny,

Went back to see how old you are in your post. My understanding is that LCIS will increase the risk of BC by about 1% each year added to your risk. Determining what your risk factor might be can be done with an oncologist or  since your mom had DCIS, a genetic counselor. According to my oncologist for someone age 50 who might expect to live 30 or more years, you would add 30% to the average risk of 10-12% and it would give someone a lifetime risk of developing breast cancer of about 40%. If your mom had DCIS, I'm not sure how that would change your risk.

Anyhow, I have been able to tolerate Tamoxifen and I couldn't handle the side effects of Femara and Aromasin. For me, the main side effect I notice is that my skin is thin and it is easy for me to get cuts. Other than that, I am not aware of other side effects. I do get depressed at times and don't know if Tamoxifen affects this for me. I had a hysterectomy so that removes one possible risk factor of taking Tamoxifen, though the increased risk of stroke is a concern for me.

The good news is that this is not an emergency and you have time to research and make a decision on what makes sense for you. I feel a huge sense of relief that after my mastectomy I do not need to worry about multiple mammograms, MRIs, BSGIs, ultrasounds and biopsies and the stress around them several times a year. 

The idea of waiting to see how the monitoring of your breasts goes might make sense. Some women do well with monitoring. But if you decide you really want surgery and your doctor does not support your decision, find a surgeon who will.

Anne,

Curious about your switch from Tamoxifen to Evista. Is Evista supposed to help with recurrence? My MO said it has less side effects but looks like Evista still has a risk of increased stroke. My MO suggested I switch but he didn't submit it to insurance and they rejected it. Cost per month is nearly $200 vs $9 for Tamoxifen. I am wondering what I will do. It sounds like Tamoxifen is more effective.

Thanks, Anne! I will keep doing research, but sounds like if this is correct, I will stay with Tamoxifen.

Hi Beesie,

That is not how my oncologist explained it to me. My understanding is that tamocifen reduced the lifetime risk. And studies I read ranged from 1-2% added risk per year for LCIS added to a woman's risk. Anyhow, need to do more reading! One more thing to study:)

For me it is balancing risk of stroke with the benefit of tamoxifen. And for me I think adding a blood thinner in the form of high dose fish oil is what I will do.

Georgie, the Atlas study on Tamoxifen that was released late last year was done on breast cancer patients and it looked at recurrence rates and mortality, so it's not the same as when someone takes Tamoxifen for a high risk situation.  Nevertheless, what the Atlas study clearly showed was that when recurrences and mortality were evaluated over a 15 year period, there was a significant benefit to taking Tamoxifen for 10 years vs. taking it for only 5 years. This was because for those who took Tamoxifen for only 5 years, while their recurrence rate was significantly reduced for 10 years, there was little residual benefit beyond 10 years.  Therefore by taking Tamoxifen for 10 years rather than 5 years, the residual benefit remained during years 11 - 15.  This study is ongoing so in another 5 years we will find out if taking Tamoxifen for 10 years had any benefit beyond 15 years. 

By applying the Atlas results to previous trials, here is an estimate of the effectiveness of 10 years of Tamoxifen vs. 5 years of Tamoxifen vs. no treatment:

What this chart is saying is that compared to those who didn't take Tamoxifen at all, the women who took Tamoxifen for 5 years had a 53% recurrence rate ratio (i.e. a 47% reduction in recurrence) over years 0 - 4, a 68% recurrence rate ratio (i.e. 32% reduction in recurrence) over years 5 - 9, and a 94% recurrence rate ratio (i.e. a 6% reduction in recurrence) from year 10 onwards.  For those who took Tamoxifen for an additional 5 years (for a total of 10 years), their recurrence rate ratio during years 5 - 9 was lowered to 61% (i.e. a 39% reduction in recurrence) and their recurrence ratio at 10 years and beyond (to 15 years since that's as far as the study has gone) was 70% (i.e. a 30% reduction in recurrence).

From this data, it's clear that the benefit from 5 years of Tamoxifen continues for another 5 years after you stop taking it (although the benefit is not as great as it is during the years when you are taking it) but beyond that,  there is little benefit left.  While this study was looking specifically at breast cancer patients and recurrence rates, it's probably reasonable to assume similar patterns of effectiveness for high risk patients who take Tamoxifen.  So what it means is that if you are 50 and expect to have another 40 years of life ahead of you, and if your cumulative breast cancer risk over these 40 years is 40%, 5 years of Tamoxifen will reduce your risk for the next 10 years (to about age 60), but not the entire 40 years till you are 90.

Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial

.

Edited to Add:  MsVeryDenseBreasts, I was writing up my post as you were posting yours.  Looks like we are saying the same thing!  .

it is important to note that, georgie, that deals with preventing recurrence in a woman already diagnosed with a known ER+ cancer. It is known their BC had estrogen positive receptors. Tamoxifen works by blocking uptake of estrogen in these receptors that could fuel recurrence. It is not addressing new primaries in those women or never-diagnosed women. 

I am in a different position than as I do not have LCIS but I have had high risk counseling on chemoprevention from a medical breast oncologist who heads a high risk program, two breast surgeons, and two genetics counselors...all at different facilities. The way it has been explained to me by all of them is that in a group of never-diagnosed high risk women taking tamoxifen there is a risk reduction in that they are estimated to have half as many bc dx's as would a group of high risk never-diagnosed women not taking tamoxifen (not quite same as 50% reduction in the individual though which is how I often seen it stated!). However, while they did say tamoxifen gave some lasting protection once tamoxifen was discontinued, it was certainly not for a lifetime. Also, they were not sure if in these high risk women taking tamoxifen there is any reduction in mortality. How is this? Well, tamoxifen may only reduce risk of being dx'd with a primary cancer that would have had lower mortality risk in first place and not those that are more aggressive and/or may have higher mortality anyway. 

Take four high risk never-diagnosed women for example. Two are taking tamoxifen, two are not. Of the women not taking tamoxifen, one develops ER- bc, one develops ER+ bc. Of the women taking tamoxifen, one develops ER- negative bc. One does not develop any cancer. How do we know the cancer free one would have developed cancer if she did not take tamoxifen? We don't. Similarly, we do not know if the ER- woman taking tamoxifen or the one not taking it were ever at risk of ER+ cancer. None of them had a risk of 100%. We know there was 50% less primary cancer in the tamoxifen group versus the non-tamoxifen group but this tells us little about the invidual woman who is cancer-free and whether she had a risk reduction. Maybe it did prevent an ER+ cancer, maybe not. But of course, comparing the groups there is a 50% reduction! Say both the ER- women die of their cancer in 3 years. The ER+ woman and the never diagnosed women die of old age at 102. So, mortality between the two groups from bc is the same. 

This is not to say tamoxifen is not right for you, OP, but it is important to know its limitations as well. Now, ER- bc is less common than ER+ cancer, but in some groups this is the reverse (ie BRCA1+ women) so tamoxifen is not one size fits all and there are issues taking results from studies on recurrence reduction in ER+ diagnosed women and applying to never-diagnosed women. 

DiveCat, my understanding of risk is exactly the same as yours.  And it was my oncologist who explained it all to me.  I was lucky because I think you are right that too many doctors don't take the time to explain this well. 

Georgie, the information you and I provided is from the same study, and it's completely consistent.  I provided recurrence rate data; you provided mortality rate data and that's the only difference.

A breast cancer mortality is the result of a breast cancer diagnosis or a breast cancer recurrence.  Therefore mortality always lags diagnosis or recurrence, usually by a few years. So it is completely logical therefore that the mortality benefit from Tamoxifen will extend for a longer period than the recurrence benefit.  In fact the study specifically notes this.  Here is the first line of the Introduction section of the full report:  

"For women with oestrogen receptor (ER)-positive breast cancer, treatment
for 5 years with adjuvant tamoxifen substantially reduces the rate of
recurrence not only during the treatment period but throughout the first
decade, and reduces breast cancer mortality by about a third throughout
the first 15 years (including years 10—14)"  

So there you have it.  5 years of Tamoxifen reduces recurrence risk for 10 years (the first decade) and reduces mortality over 15 years.  

You can see this lag effect on mortality rates in the data chart that I presented in my previous post.  When I was writing, I detailed only the recurrence rate data, but the mortality data is right there below the recurrence rate data in the chart.  It shows that taking Tamoxifen for 5 years results in a mortality rate ratio of 71% over years 0 to 4 (i.e. a 29% reduction in mortality), a mortality rate ratio of 66% in years 5 to 9 (i.e. a 34% reduction in mortality) and a mortality rate ratio of 73% from 10 year onwards (to year 15; a 27% reduction in mortality). Those who added the extra 5 years of Tamoxifen lowered their mortality rate ratio to 64% (i.e. a 36% reduction in mortality) in years 5 to 9 and to 52% (i.e. a 48% reduction in mortality) in years 10 onward (to year 15, since that's as far as the study has gone so far).  

A couple of significant points.  First is that the mortality reductions are not as great as the recurrence reductions.  This makes sense since many recurrences can be successfully treated.  Second is that you can clearly see that mortality benefit lags recurrence benefit.  For those who took Tamoxifen for 5 years, their largest mortality rate reductions were in years 5 to 9. This is because (as the data shows) Tamoxifen provides the largest recurrence rate reduction during the years that you take it, years 0 - 4.  The women who were able to avoid recurrences while taking Tamoxifen therefore benefited by having fewer breast cancer deaths over the next 5 years.

The reason I focused my earlier post on the recurrence rate benefit is because I think that's more comparable to the situation of high risk women who are trying to avoid the development a new breast cancer.  Just as someone who's had breast cancer wants to avoid a recurrence, someone who is high risk wants to avoid an initial diagnosis.  By avoiding the development of breast cancer, you never have to worry about breast cancer mortality.  The mortality reduction from Tamoxifen is really an indirect benefit rather than direct benefit; the mortality reduction exists only because the recurrence or new primary diagnosis never happened. So the period during which Tamoxifen is providing the direct benefit is the first 10 years (for those who take Tamoxifen for 5 years) or the first 15 years (for those who take Tamoxifen for 10 years).  The mortality benefit over the next 5 years in each case is simply the fall-out from the lower recurrence and cancer rates. During those next 5 years, although the mortality rates are lower, the recurrence rates and new diagnosis rates are only minimally reduced because Tamoxifen is no longer providing the same level (or a significant level) of recurrence or new cancer reduction benefit.

MsVeryDenseBreasts, thanks!

I tend to get complicated in some of my posts and since I wrote my post this morning, I've thought of a very simple way to explain why the 15 year mortality benefit really isn't relevant for someone who is high risk.

If you are high risk and you take Tamoxifen, you are taking it specifically in order to stop the development of breast cancer.  If you don't develop breast cancer, your breast cancer mortality rate is 0%. The only situation under which you have to worry about breast cancer mortality is if you do develop breast cancer.  And if you do, it means that the Tamoxifen didn't work.  

That's why someone who is high risk should be looking at how long Tamoxifen is effective at reducing breast cancer occurrence, and not at the extended benefit on mortality rates.  

I have just had a lumpectomy and have LBIS. My appointment with my oncologist is next week.  I have no history of breast cancer in my family.  These drugs sound so horrible.  My Dr. told me to come back for a mamo in a year, and to go talk to the oncologist.  Is there anyone who hasn't taken these drugs, and hasn't gotten cancer?  I wonder if there is a more natural approach, like Gerson Therapy thru nutrition, that could help.  This is so frightening, and any advice is welcome.  Thank you all

Suzanne, I have LCIS (diagnosed 4/08).  I have opted not to take Tamoxifen.  I've chosen close monitoring instead.  I have no family history of breast cancer (and a long history of female longevity), and no lifestyle or genetic risk factors.  I do have extensive family history for some of the most serious possible side effects of Tamoxifen (i.e. stroke, eye problems etc.) and I am not interested in running the risk of inviting problems I do not already have.  I constantly re-examine my decision against any new data that comes out in case a change of mind is warranted by new health or study circumstances. My surgeon agreed that Tamoxifen would be overkill for me and frankly I am fairly skeptical of big pharma when it comes to this sort of thing.  Unfortunately, as with everything we are dealing with here, it comes down to evaluating the medical info in the context of your own circumstances and trusting your gut with the decisions you make.  Another reason I opted against Tamoxifen is because the situation that generates studies/biopsies in my case is the appearance of clustered calcifications.  As my surgeon acknowledged, Tamoxifen is not going to prevent my body from forming these calcs because the docs don't know what causes it….so, if the standard of care is always to biopsy clustered calcs, I thought, "why bother with the quality of life impacts (and other more serious side effects) Tamoxifen can have".  I'm not a terribly anxious type so for now I'm comfortable with this choice.  Best of luck to you. 

leaf, the way I look at the example you provided is that for those who took Tamoxifen, the percent who developed pulmonary emboli was 1.13% (18 of 1596 patients).  Of those who took the placebo, the percent who developed pulmonary emboli was 0.34% (6 of 1782 patients).  So while there is a very significant increase in the risk to develop pulmonary emboli (more than a 3-fold increase in risk), the absolute risk remains very low.

In addition, I believe that the Tamoxifen studies have shown that the women who tend to develop these very serious side effects often started off being higher risk for these conditions. So if you start off with no risk factors for pulmonary embolism, then your risk from Tamoxifen is probably lower than 1.13%.

Yes, I agree - my point being that if you are concerned about having a pulmonary emboli, the absolute incidence of having a pulmonary emboli, whether or not you take tamoxifen, is quite low.  The number (18) with tamoxifen is quite a bit higher than without tamoxifen (6).  You do have to compare the incidence in the placebo group and the treatment group.  I just wanted to point out that some people, in their understandable fear, may assume incorrectly that everyone, or a large percentage, of those who take tamoxifen will get a serious adverse effect.

glorianna--I had a bad yeast infection very early on when I first started tamox, but cleared up with diflucan and never happened again. My main SE was hot flashes, but they were mild.  I did develop large ovarian cysts which ruptured (but that is a long story and it is a very rare SE); it is a good idea to have a yearly transvaginal US when on tamox to monitor both the uterine lining and the ovaries. The risk of any serious SEs is actually very low (<1%), tamox is generally pretty well tolerated by most.  I was willing to take the very low risk of serious SEs, in order to decrease my high risk of invasive bc from my LCIS and family history of bc. We each have to look at our own situation and decide what is right for us individually.

anne

Personal anecdotes can be helpful but the problem when people talk about their personal experiences with a drug is that you have no idea if the drug actually caused those issues.  

leaf, that's what's so great about the information you provided. As you said, "You do have to compare the incidence in the placebo group and the treatment group."  Looking at the list of side effects that you provided, it's easy to see that whether someone took Tamoxifen or whether someone took the placebo, they had the same list of "side effects", to a greater or less degree.

Within a year or so of my diagnosis of breast cancer, I suffered hot flashes and particularly, really bad night sweats.  I also had vaginal bleeding and required a D&C.  Oh, and I didn't take Tamoxifen. I just was entering menopause.