Minimal benefit from Letrozole

[laneycass]

Hi all, I started on Letrozole three months ago with the view that if the side effects were tolerable and settle down then I may as well take it. I have tolerable side effects but they are unpleasant so I don’t necessarily want to keep taking it if they continue. I was also offered bisphosphonates to counteract the long term side effects (osteoporosis) and reduce my risk of bone metastasis. I have been astonished by the lack of information from oncology on statistics that back up the prescribing of these pretty nasty drugs. I used Predict which gave a miniscule increase in my chances of five and ten year disease free survival with these drugs. I wrote to an eminent academic who’s stats were miles away (much more compelling) than those suggested by Predict. I don’t understand why the oncology stats vary from the academic stats as they should stem from the same source.

So my questions to anyone who has a view are: Why do oncologists think nasty drugs are worth taking for almost no additional benefit? Why do so many people take Letrozole when the benefits seem to be massively outweighed by unpleasant side effects and other debilitating long term conditions. Is it that people just blindly trust what they are told or am I missing something? It would be easy to go down the conspiracy theory route that there is simply big money to be made in big pharma!!

Is there anyone out there who has declined Letrozole because of a perceived low benefit vs risk? I would love to hear from anyone else who is further down the line having declined it, from anyone who is having similar concerns or from anyone who understands and can help me to get the answers I need to make decisions for my long term treatment.

Thanks All

[Bookie]

Hi

This is an interesting post - did the expert that you conducted suggest that it is not worth taking Letrozole and how did his stats differ from Predict figure wise?

I was under the impression having read a number of journal articles that letrozole has been widely researched as an aromatase inhibitor and is very successful in helping to reduce recurrence rates. This includes research where recurrences have happebed as a,result of non compliance.

Best wishes

Bookie

[laneycass]

Hi Bookie, the experts figures suggested considerable benefits for bisphosphonates, particularly for post menopausal women in terms of metastasis prevention. But the oncology team and Predict suggested 3% or even less in terms of increased chance of disease free survival.

With Letrozole the Predict tool didn’t offer much more of an increase. I’d have to check all figures and I realise that I am conflating Letrozole and Bisphosphonates but, for me, there was certainly nothing to suggest significant benefit (from oncology or Predict) from either drug. The oncologist argued that 3% is considered significant in medical terms - that’s what really threw me, why do they consider that significant? Are you able to point me to journal articles? I’d be really interested to read more. Thanks

[JoanneN]

Hi @laneycass

I would be interested to know where your info came from - is there a paper I could access from the academic you mentioned.
From the evidence I’ve read Aromatase Inhibitors are on the whole effective at stopping recurrence / development of new primaries and also for secondary breast cancer.

I was on Anastrozole but abandoned it after about 5 months . My reasons were that I had a tumour that was very small early Grade 1 and of a type ( tubular) that rarely spreads . I’ve read other research that says people with my kind of cancer of less than 1cm ( mine was 1cm) shouldn’t automatically need hormone therapy. My Breast Consultant also said at the start that he felt it would be reasonable to stop though I know my Oncologist ( who had discharged me by the time I stopped) wouldn’t be pleased. My Predict score only improved by 0.8% over 5 years to 1.3% over 15 years .

Finally I was struggling with joint pain and stiffness and hair thinning as well as hot flushes.
I also have some underlying health problems which I felt might be aggravated by continuing to take Anastrozole and cause complications.

However I do sometimes wonder if this is the right decision. I’m trying to improve my lifestyle but I’m an ideal candidate to get another one. Age ( 58) weight - too much ! Children - none, tall . Plus already had one cancer . I did try taking it at night instead of morning - that just shuffled the symptoms about a bit but I could have properly discussed it and considered options like taking it on alternate days / twice weekly . I believe this is not recommended but still thought to be safer than not taking it at all - I wasn’t aware of this possibility at the time.
If my cancer had been more aggressive and my Consultant had not said what he said and my Predict score was higher I would not have stopped when I did.

There are many threads about AIs on this forum discussing side effects benefits and research - I don’t think anybody just takes it blindly. A lot of people who don’t have side effects don’t post so it’s easy to think that everyone gets them.
Whether you take it / don’t take it or take it and and decide to stop I think it’s a decision we all weigh up very carefully .

Whatever you decide make sure you don’t just follow research that comes to the conclusions you like better - it’s an easy trap to fall into .

Joanne

[Bookie]

Hi Laneycass

I think predict very much depends on your individual bc profile so for me with a grade 3 oestrogen sensitive tumour and a positive lymph node the benefits were much higher. To find journal articles I just searched Letrozole and breast cancer on google scholar and several journal articles came up. The research shows letrozole to be very effective.

Best wishes

Bookie

[laneycass]

Joanne, thanks for your considered response. It was the academic that gave an optimistic view on outcomes. I read a number of papers by Prof Coleman at Sheffield Hallam Uni and then wrote to him for some clarification. It was Predict and Oncology that gave such low levels of potential benefit. My diagnosis is somewhat worse than yours and does (they say) require hormone therapy but my Predict scores are in the same ball park which doesn’t make any sense to me.

I am 59, not overweight but already have joint pain issues with sciatica and arthritis so I definitely don’t want to increase my chances of getting osteoporosis for no significant recurrence risk reduction. I also have no children and I am tall but had no idea either of these were significant factors. Perhaps reducing the dose with alternate days is an idea worth pursuing, thanks for that. I was always told you couldn’t do that with HRT but I eventually did it of my own accord - obviously far too late though!!

Sadly I think some people do blindly accept what they are told, I know a few folk like that. Not me though, I have had too many bad experiences with the NHS and in any case my anxiety probably drives me to check every detail. It is definitely the right approach for me.
Laney

[emsj]

My BC is her2+ and “weakly” oestrogen +. I was originally told that I would be having TCHP followed by radiotherapy and then letrozole. This was from the breast surgeon when he got the pathology report (surgery before chemo as originally diagnosed with DCIS).
My first onco appointment was for the most part with the registrar who also said they were treating me as oestrogen positive and that letrozole would be beneficial, predict scores were much more positive with this than for just HER2+.
Saw the onco last week who now says letrozole won’t be beneficial as I’m only weakly oestrogen positive, it will only give a 1% benefit and he would be happy if I chose not to have it. He is recommending bisphophonates as I am post menopausal to help prevent bone mets. This gives 2% benefit according to predict.
I think the benefit of letrozole increases significantly if your oestrogen positivity is high.
To be honest I feel like I’m going through initial diagnosis again as my predict score has now gone down by 20% when it is only for her2+, which really sucks. Wish they had told me that from the start tbh.
Also it’s now left to me to decide about letrozole, but if it’s really only a 1% benefit I doubt I will take it.
If there is more info available I would like to see it too please.
X

[helen39]

Predict stats are based on tamoxifen, not an AI. You can read on the technical section how old they are

[JoanneN]

Hi again @laneycass

Thank you for the information - I will look up that gentleman . Thank you @helen39 for the info about the Predict score - I wasn’t aware of that .

I can’t say I’m recommending taking an AI alternate days - just that I’ve become aware from other posts that some people are doing it , I’m sure you will find this info yourself if you continue to use the forum . I’m assuming those people have discussed it with their teams first and hope you will too before you do anything. My BCN was supposed to ring me to discuss it but for whatever reason they didn’t though I did make them aware .

My first visit to the centre where I had my recall mammogram there was a list of risks factors on the wall and being tall was listed though near the bottom of the list . However at my BC support group we were every shape and size and both sexes.

Take care
Joanne

[laneycass]

Hi thanks for responding. I had that too, where they told me it was DCIS and then moved the goalposts after pathology reports on the removed tissue. I found that particularly difficult to deal with emotionally. I think it would be better for them to be clear at the outset that they really don’t know what your diagnosis is until they see it under the microscope.

What is your view on the Bisphosphonates? I am terrified of getting jaw necrosis which (according to oncology) is a 3% chance - that is the same as the improved DFS chances. However the stats I was given by Prof Coleman again are wildly different (he said the chance of getting JNC are 1/1000).

[emsj]

I nearly passed out when I was told the pathology report, it was one thing after another, from 21mm DCIS it went to 11mm invasive, there was also an unexpected intramammary lymph node + for cancer in there, then said oestrogen positive, all this just sinking in and he added the her2+.
I’m also terrified of the jaw necrosis. I’ve got a few weeks to think about it. Still have radiotherapy to do. At this point I’m a bit confused.

[Tigress]

Hi @laneycass I’m interested in why you think that a small percentage increase in protection from endocrine treatment is negligible but an equally small chance of jaw necrosis from bisphosphonates is material. Is this the anxiety talking?

I agree that deciding what to believe and what to do is extremely stressful. I have been taking Letrozole for a year now, just turned 68 and had Grade 1 IDC which was ER+ 8/8 PR+ 6/8 HER2- with integral DCIS. My side effects are largely cognitive - brain fog, fatigue, low mood - although the joint pain is beginning to make itself known.

I did the Predict test with the MacMillan nurse at the hospital, results were 0.2%, 0.9%, 1.2% increased protection over 5, 10, 15 years on 5 years of endocrine treatment. So, like most people, I wondered what the point of taking it is, particularly as the results are based on Tamoxifen studies and it is well known that, for post-menopausal women, an AI offers better protection than Tam. Presumably the risk is even less in that case? My concern is that I do not want to hasten any cognitive decline by taking Letrozole as there is so much dementia in my family (there have been no long term studies to determine whether AIs do impact the brain, so we are told it doesn’t purely because there is no evidence either way) but that seems to be where I’m heading if the SE are to be believed.

I still take it, however, because Predict is largely a basic indicator of survival rather than recurrence. There is nothing in there about co-morbidities or metastatic breast cancer. For example you may have a 98% chance of being alive in 10 years if you don’t take the drug, according to Predict, but you may be living with secondaries. Conversely, you may be taking it for 5 to 10 years and die of something unrelated in the meantime.

I think what I’m trying to say is, I applaud you for researching potential outcomes in the way you have but there are so many variables in the equation, it is impossible to calculate an accurate outcome with any precision. Therefore, it might be worth giving the Letrozole a go before dismissing it as, if the length of survival is virtually identical, taking it in combination with the bisphosphonate, could mean those years are lived with out secondaries. If you cannot tolerate one or both, that is the time to reject them? In the end you just have to be able to live with the consequences of whatever decision you take.

[teddy271]

I could have written exactly the same post some months back. I had a mastectomy/chemo/radiotherapy/letrozole/surgery and continually questioned my oncologist about the efficacy of this nasty cocktail.

I think we need to remember that the oncologist’s job is to keep patients alive for the longest possible time - and it is fair to say that this objective is shared by most of the patients they treat. I was in my early seventies leading an active business and social life and had no desire to have treatment that although life saving, might give me a poor quality of life. My oncologist found this hard to understand - when he told me chemo would give me an extra 4% on expected lifespan I nearly fell off my chair as, in my ignorance, I thought it was a cure-all. Eventually I wrote to him explaining that I was single with no dependents and describing how I liked to live. I think he got my point but was adamant that chemo and radiotherapy were necessary so I took his advice. Chemo was horrid but doable and radio is a breeze.

However, I did not tolerate letrozole at all well and hated the way it made me feel. Ditto bisphosphonate which, for me, was much worse than chemo. I seem to have been the 1% who gets an adverse reaction and it took me nearly three months to feel anything like well again so I abandoned this after just one treatment. I have also given up letrozole although I didn’t do this lightly. I simply didn’t want to live the life of the invalid it made me become although in fairness most people cope. I was the wimp.

My cancer was already quite advanced by the time it was diagnosed thanks to the NHS having cancelled mammograms during Covid. It was also of an aggressive type so I came to accept that every little percentage point through the major interventions that the medics could give me re prolonging my life was worth it . But NOT the long term treatments that I found from experience were totally debilitating. This is an intensely personal decision and each of us must decide for ourselves what we think is best.

Wishing you all the best.

[laneycass]

Hi Tigress, you picked up on my point but in reverse, what I was thinking is why do the medics think 3% is a significant benefit on the one hand (prevention of recurrence) but tiny risk on the other (risk of JNC).

I didn’t know that stuff about Predict, thanks for that. I thought that it was speculating on disease free survival for Letrozole (I’m going to have another look at it to check but that’s what I thought I put in. I will talk it through again with the oncologist.

I already have a number of side effects from Letrozole, the worst is the joint pains. I already had a lot of those so I am now on another level. I am surprised you say they are kicking in with you after a year, could that be something else or is that the osteoporosis starting? Did you have bisphosphonates? I was told that side effects settle down but I have yet to hear from someone with that experience.

The worrying bit is cognitive impairment, brain fog but also the wrong words come out. I am only 3 months in and I say things that come out differently to what I intended, I think that is really strange.

I think the source of anxiety is, as you say, the consequences of my decision. One of the nurses said to me ‘you don’t have to take the drugs, you just need to ask yourself how you would feel if the cancer came back.’ That, I thought, was really odd because the predict benefits are so low that they won’t have much influence on whether or not it comes back. The way I am looking at it appears to be the polar opposite to all the professionals I have spoken to.

You and others on here are helping me to figure things out, it’s thought provoking to hear different perspectives. I will get there …

Thanks

[laneycass]

Thank you, this is really helpful. I am so sorry you’ve had such a crap time with it all. Take care xx

[teddy271]

Thank you. I am much better now and leading a pretty full life. My view is that I did all the major treatments to give myself the best chance of survival but I didn’t want to prolong life at the cost of actually living it. It’s fair to say this is an unusual response as most people are fixated on longevity. This is why I wrote to my oncologist setting out what I wanted to achieve. I should add that had I been thirty years younger or had children, I might have taken a different decision. I take the view that if it comes back some years hence, well at least I’ve lived my life. But we are unusual in our thinking.

[Tigress]

Hi @laneycass apologies for misunderstanding your first point. Interacting with many women and one male friend with BC over the past 15 months, I am quite clear that SE from endocrine treatment can go one of four ways - experience SE from the beginning, experience SE but they become less as the body adjusts to loss of oestrogen, don’t experience SE to any noticeable degree, don’t experience them to begin with but begin to after a year’ cumulative impact of loss of oestrogen. For me, the cognitive impact started within weeks but the joint pain has just kicked in. It frankly cannot be anything else. It’s perfectly bearable at the moment. We are all told when we start that any SE will pass within 6 months to a year but that is not the lived experience of many women. It’s just another demonstration that we can all react differently to our treatment and the medics cannot accurately predict how we will respond. But then, no-one said having cancer would be easy. If you decide to discontinue, as many do, please discuss with your medical team first.

I, rather surprisingly, have no osteoporosis or even osteopenia, according to my recent Dexa scan so haven’t been forced to decide on bisphosphonate treatment. I’m not sure I’d go for it.

All I will say about Predict is that it is a useful tool in predicting survival but should not be relied upon when predicting quality of life. 30% of women with early stage BC in the UK go on to develop secondaries and it is virtually impossible for the medics to predict who that will be. To put it bluntly, it can be a choice between quality or quantity of life but in the end, it’s all a gamble, none of us can ever know at the beginning what the outcomes will be and each of us has to decide, when considering adjuvant treatment, what is most important to us. Perhaps you are looking for reliable, concrete data on which to make your decisions but there are none. As I said, having cancer is not easy.

I wish you all the best in your recovery.

[teddy271]

Just want to say how well you have expressed the dilemma many of us face. In today’s world we reach for solutions but cancer is a slippery demon, the treatment often baffling with little logic and even less certainty. To put it bluntly, cancer medicine is still groping in the dark and many of the treatments border on barbaric. But right now they are all we’ve got.

I abandoned letrozole and bisphosphonate because they made me feel completely parc and I didn’t want to live that way. I reckon there is a pretty good chance of it returning but I’m gambling that this will be some years hence. In the meantime I am living every moment and mostly don’t even think about cancer.

[Tigress]

Hi @teddy271 I have read through your posts on this thread and just wanted to say - for what it’s worth - how much I support your viewpoint and decisions. My dx was aged 66, I have just turned 68. I have taken Letrozole for a year with a break in the Spring to sort out VA and am due to take it for 4 more years. It is highly unlikely that I will. I have thought about this thoroughly during this period and would be satisfied with another 10-12 years if possible as my most dreaded outcome is developing dementia like many women in my family, including my mother. Like you, I have no kids and am the youngest in what family there is left and amongst my closest friends so living beyond 80 with dementia and no close people to take decisions for me is my worst nightmare. Obviously I would prefer not to die from either cancer or dementia but the odds are it will be one or the other. I don’t want it to be dementia. I can’t even contemplate the cancer coming back when I have dementia.

I just thought I’d share part of a post from an ex-forum member, Appletree, an older lady who went through the same thought processes as yourself. She discussed it with a senior doctor who said “Cancer treatment efficacy is always measured in terms of 5 or 10 years survival whereas for many other medical interventions we look at QALYs (quality adjusted life years) which takes quality of life into account. We have conditioned people to aim for cancer elimination almost at any cost as it is assumed that living with it is too fearful. In reality it is no different to any other chronic condition that people may live with. This has come about because the big advances in cancer treatment have been with childhood cancers where aiming for a cure is entirely reasonable. Priorities and decisions are very different at the other end of life.” Appletree ceased taking Anastrazole after this discussion and, whilst I am not yet at that point, I will bear these words in mind as I move forward.

You deserve the quality of life that you have always enjoyed, not least because of your bravery and clear-sightedness. I hope you are rewarded with quality AND quantity.

[teddy271]

Thanks for your kind words. This is such a difficult issue with no clear cut answers. I have always trodden my own path and was completely anti Lockdown because it seemed to me we were stopping living to save life. A sort of Faustian pact: do as the government says and you’ll live forever - if you can call it life. I remain shocked that so many people bought the propaganda and became sheep. I think we see the results all around us now with the country in terrible shape.

However, back to cancer, I remember meeting ladies in chemo who were in their eighties. Skin and bone and fragile, enduring the hell of chemo when in my view they should have been at home drinking champagne!

I resonate with your post and hope you are doing okay. Like you, I fear not being able to look after myself so in a strange way I almost don’t mind the thought that the cancer will probably get me in a few years time. Meanwhile there’s a lot of living to be done.