Don't want AO--anyone else?

Anonymous

Don't want AO--anyone else?

beautycountershari

Hi there! I meant Aromatase Inhibitor.....A

I just finished rad 16 and 4 boosts, I am 57, fit, athlete however I have had 2 back surgeries and deal with pain. I do not want to take aromatase inhibitors due to the side effects; especially because they only give a person an extra 4% in statistics. My mammoprint showed the lowest type (least aggressive) cancer, stage 1, no lymph nodes.....lumpectomy. I feel pretty blessed to catch things early . I am making more changes to my diet (it's pretty healthy to begin with) but am tired of the pressure to go on these drugs. I deal with too much pain already, I have no interest.

Anyone else feel this way and any tips with herbs/diet appreciated. This girl just wants to live life playing tennis, doing yoga, walking and strength training without crummy side effects.

ElaineTherese

Hi! There are already several threads about your very situation. See, for example, https://community.breastcancer.org/forum/78/topics/843659?page=6#idx_173 or https://community.breastcancer.org/forum/121/topics/791646?page=66#idx_1951.

You may benefit from reading through the existing threads. Personally, my side affects from Aromasin are mild (some hot flashes). It's different for everyone, and you'll never know how you'll react to an AI unless you try one. Best wishes!

BarredOwl

Hi beautycountershari:

Formally speaking, as a post-menopausal woman, you have the additional option of Tamoxifen, which has a different side effect profile.

The following is not a comment on your decision, but is intended to provide general information regarding "absolute benefit".

(1) Re: "especially because they only give a person an extra 4% in statistics"

Please provide a link to the clinical trial that you are relying on for a reported "4%" statistical benefit of Aromatase Inhibitors.

The "absolute benefit" of any particular endocrine therapy observed in various clinical trials varies according to the particular endpoint assessed (e.g., recurrence, mortality, etcetera); time point (e.g., at 5 years, 10 years, 15 years); patient population (e.g., ER+ versus ER-? "High risk" patients with no breast cancer diagnosis? DCIS patients? Early stage breast cancer patients? Locally advanced or metastatic patients?); and comparator (e.g., placebo, comparator drug).

Thus, a reference to "4%" statistical benefit without any of the above details is a relatively meaningless statement, and is potentially misleading to those with pending treatment decisions.

In any case, for the purpose of treatment decisions, CASE-SPECIFIC estimate(s) of the absolute benefit(s) of any proposed endocrine therapy regimen over no additional treatment should be provided as part of a personalized risk/benefit analysis (See (3) below). This information should be based on an estimate(s) of YOUR recurrence risk(s). If you have not been provided with such information, please request it.

(2) Absolute Benefit of Aromatase Inhibitors ("AIs") in Early Stage (Invasive) Breast Cancer

For patients considering INITIAL endocrine therapy, clinical trials evaluating five years of an AI-containing regimen in the adjuvant setting of early stage invasive breast cancer are of two main types:

(1) 5-year "Monotherapy" regimens of an AI compared with 5 yrs Tamoxifen

(2) 5-year "Switch" regimens (e.g., 2 yrs Tam followed by 3 yrs AI) compared with 5 yrs Tamoxifen (or an AI)

To my knowledge, the various AI trials (e.g., ATAC, BIG 1-98, etc.) did not compare an AI to no endocrine therapy. They compared new AIs (or AI-containing switch regimens) to another endocrine therapy regimen (e.g., 5 yrs Tamoxifen). This is because clinical trials use the existing standard of care as comparator when a placebo-controlled trial would not be ethical.

The "absolute benefit" observed in such trials reflects the comparable activity or modest advantage of an AI (or an AI-containing switch regimen) versus the comparator regimen (e.g., 5 yrs Tamoxifen), and NOT the benefit of an AI over no treatment.

The absolute risk reduction benefit of AI monotherapy versus no endocrine therapy would be expected to be substantially larger than the absolute benefit of an AI over Tamoxifen reported in such trials.

(Note: Certain extended therapy trials (of treatment beyond five years) were placebo-controlled. However, the patients all received an initial five years of endocrine therapy, and only then were randomized to receive either an AI or placebo for an additional five years. The extended therapy trials do not speak to the benefit provided by an initial 5 years of endocrine therapy versus no treatment.)

So, what is the absolute benefit of about 5-years of Tamoxifen? Based on the EBCTCG 2005 study, Dowsett notes:

Dowsett (2010), "Meta-Analysis of Breast Cancer Outcomes in Adjuvant Trials of Aromatase Inhibitors Versus Tamoxifen"

http://ascopubs.org/doi/full/10.1200/JCO.2009.23.1274

"In the trials studying approximately 5 years of adjuvant tamoxifen versus no tamoxifen in ER-positive disease, the main effect of tamoxifen on breast cancer recurrence was seen in the first 5 years (absolute gain of 12.5% at 5 years and roughly constant thereafter), but the main effect on breast cancer mortality was seen later (absolute gain of 3.3% at 5 years and 9.1% at 15 years)."

The results of the later EBCTCG (2011)(see link below) re about 5 years of Tamoxifen were consistent:

Figure 5 (left), the 15-year gain (or absolute difference in recurrence) is printed under the curves:

"15-year gain 13·2% (SE 1·1)" in Recurrence

Figure 5 (right), the 15-year gain (or absolute difference in mortality) is printed under the curves:

"15-year gain 9·2% (SE 1·0)" in Breast cancer mortality

The reported 13.2% absolute benefit at 15 years with about 5 years of Tamoxifen treatment is based on the absolute difference in recurrence between two groups (Tamoxifen versus no endocrine therapy). Yet estimates of absolute benefit for individual patients may be the same, lower, or higher, depending on their individual recurrence risk.

(3) The Benefit(s) of Endocrine Therapy are Proportional to INDIVIDUAL Risk

The absolute benefit observed between two patient groups under comparison in a clinical trial of endocrine therapy is not the most relevant factor in treatment decisions, particularly if the groups are relatively diverse in terms of risk profile. This is because because the benefit of endocrine therapy is proportional to individual risk. For example, with Tamoxifen:

EBCTCG (2011): "Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials"

Main Page: http://thelancet.com/journals/lancet/article/PIIS0140-6736(11)60993-8/abstract

PDF version: http://thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60993-8.pdf

Supplementary web appendix: http://thelancet.com/cms/attachment/2001012705/2003807448/mmc1.pdf

=====> "Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen."

This means that those with greater residual risk after all other treatments potentially reap larger absolute benefits than those with lower residual risk.

The "relative risk reduction benefit" (in reducing recurrence) of five years of initial monotherapy with an Aromatase Inhibitor in early stage invasive breast cancer (versus no endocrine therapy) is often given as ~50% (often given as ~45% for Tamoxifen).

Example: With an estimate of individual 10-year distant recurrence risk (after chemotherapy, if any) ("RISK"), one can calculate individual absolute benefit in reducing said risk:

(RISK (%)) x (relative risk reduction benefit; e.g., 0.50 if 50%) = (absolute risk reduction benefit of AI (%))

(RISK (%)) - (absolute risk reduction benefit) = (residual recurrence risk with AI (%))

=====> Because potential benefit is proportional to individual risk, patients should always seek case-specific advice from their medical oncologist regarding their estimated recurrence risk(s) after all other treatments, the potential relative risk reduction benefit and estimated absolute risk reduction benefit(s) of any proposed endocrine therapy regimen (versus no treatment) in their particular case. This in turn is weighed against the risks of treatment in a personalized risk/benefit analysis.

In early stage invasive breast cancer, endocrine therapy can reduce the risk of mortality, the risk of distant (metastatic) recurrence, as well as the risks of loco-regional recurrence or new disease (a new primary in the same or contralateral breast). Patients should be sure to ask about the type of any risk estimate(s) provided by their medical oncologist. Write the information down and have your MO confirm the accuracy of your notes. For example, what type of recurrence risk is being discussed? (5-year? 10-year? Mortality? Distant recurrence? Other?)

BarredOwl

---

Additional Miscellaneous References:

ATAC (10-year analysis): (Ana) versus (Tam) versus (Tam + Ana);

Cuzick (2010): http://thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract

BIG 1-98 (8.1 years median follow-up): (Let) versus (Tam) versus (Tam + Let) versus (Let + Tam);

Regan (2011): http://thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(11)70270-4.pdf

ABCSG-8 (median follow-up of 60 months): (Tam + Ana) versus (5 yrs Tam)

Dubsky (2012): http://ascopubs.org/doi/full/10.1200/jco.2011.36.8993

Momine

Barred Owl, given the posters stats, the 4% benefit may well be accurate. As best as I remember, hormone therapy halves the remaining risk after surgery etc. With a stage 1 cancer, low-grade, it sounds about right that the remaining recurrence risk is around 8%, possible even lower. That would give a 4% benefit in absolute numbers in her situation. I think it is a tough call. That said, my SEs have also been entirely minor, so it would probably be an idea to give the druga try at least.

movingsoccermom

On the other hand, my side effects were not sustainable, and I quit AI's after a 10 day trial. Vertigo was so bad I was not able to drive a car, not a way for me to live. Many women seem to have no trouble though, so a trial was worthwhile to me.

Best of luck!

Momine

Movingsoccer, sorry for your troubles. I know many women have a rough time with the AIs.

BarredOwl

Hi Momine:

Thanks, and I considered that possibility (similar to my own situation). Note that I expressly did not question the decision, recommending only that if the "4%" is not a case-specific estimate, that such estimates be obtained:

"The following is not a comment on your decision, but is intended to provide general information regarding "absolute benefit"."

"If you have not been provided with such information [case-specific estimate(s)], please request it."

Usually, people make clear the personalized nature of a case-specific estimate using phrases such as "my recurrence risk" or "in my case." In contrast, the statement "especially because they only give a person an extra 4% in statistics" is broadly written and could be read (or misread) to imply that this is a generally applicable proposition, regardless of individual risk (which it is not).

There have been a series of posts in recent months regarding absolute benefits of endocrine therapies from clinical trial publications, and members have posted questions on the "low" absolute benefits in other threads. It seems to be a common area of misunderstanding.

Thus, the main goal of my post was to clarify for "those with pending treatment decisions" that:

(1) The "absolute benefit" of any particular endocrine therapy reported in various clinical trial publications varies according to the particular endpoint assessed; time point of assessment; patient population; and comparator (e.g., placebo, comparator drug).

(2) In the setting of early stage invasive breast cancer, because AIs were compared to other regimens (not to placebo (no treatment)), the modest "absolute benefit" of AIs versus various comparator regimens (e.g., 5 yrs Tamoxifen), does not represent the total absolute benefit of an AI over no treatment. AIs have shown comparable activity to or small advantages over Tamoxifen (see my post above for reported absolute benefits of about 5-years of Tamoxifen (versus no endocrine therapy) from the EBCTCG (2011) meta-analysis).

(3) Because potential absolute benefit is proportional to individual risk, patients should always request case-specific advice from their medical oncologist regarding estimated "absolute benefit" of adjuvant endocrine therapy based on their recurrence risk profile after all other treatments.

With case-specific estimates in hand, individual risk tolerance is also a factor in decision-making.

BarredOwl

---

Edit: By the way, even within the subset of hormone receptor-positive, HER2-negative, Stage IA disease (pT1 N0 M0), due to differences in tumor biology, recurrence risk profile (and the potential benefit of endocrine therapy in reducing distant recurrence risk) may differ materially (e.g., differences in tumor biology as reflected, for example, in the recurrence risk profiles of those with very low Oncotype Recurrence Scores (RS) (e.g., 5) versus those with RS in the high risk category). And, for those with identical recurrence risk profiles, the residual recurrence risk of one who received chemotherapy would be predicted to differ from the residual recurrence risk of one who did not.

Momine

Barred Owl, oh I know. Wasn't criticizing at all. Just adding my 2 cents. It is one of those decisions that I think depends greatly on personal risk profile, as you point out.

dtad

beautycounter....as always whenever someone posts that they do not want to do anti hormone therapy there are many posts that advise against it. Can we please try to support each others decisions? The women on this forum are intelligent and mostly well informed. So to answer your question I have decided not to do anti hormone therapy. I'm 2 years out and so far so good. There are certainly no guarantees either way. I have lost 30 pounds, exercise daily, and take DIM, melatonin, mushroom extract, baby aspirin and berberine. Good luck to all navigating this complicated disease.

obsolete

Hi Beauty, so very sorry you're finding yourself here, but you are not alone in your thinking. It's crucial that YOU believe in your TX, regardless of what rhetoric you are fed... and you obviously do, so you ought to do very well, especially given your scenario. Yes, it's important that we, as a sisterhood, support one another.

Please read book or view YouTube video entitled "BIOLOGY OF BELIEF", Bruce Lipton PhD. Suggestions:

Nutrition & diet:

http://www.hoffmancenter.com/downloads/salad&salmonhandout.pdf

https://elynjacobs.com/2012/01/15/natural-alternat...

http://www.womens-health-advice.com/estrogen.html

Estrogen considerations:

http://drhoffman.com/wp-content/plugins/post2pdf-c...

http://www.naturalproductsinfo.org/index.php?src=g...

Unfortunately probability statistics are generally just that. Data from trials & studies are often substandard, especially those using misleading short-term "surrogate endpoints" vs clinical endpoints and misleading "relative" vs absolute benefits, etc. The devil is usually in the detail. It's all in the reader's perspective and in the patient's psyche, from which all disease stems (in my humble opinion). Also some patients find it helpful to monitor their E2 levels (high sensitivity estradiol blood tests) at 3rd party labs. Best wishes to you!

Momine

dtad, I don't think it is so much advising against it. It is more advice to consider all parameters and not make the decision based on fear of what the drug might bring. As I said above, with a low-grade, stage 1 cancer, I do think it is a grey area. Yes, the drug will add protection, but it is protection from a risk that is small to begin with.

dtad

Momine...my point was that the poster was looking for anyone else that had decided not to do anti hormone therapy NOT a reason why she should consider it. She was looking for alternative methods of dealing with her BC. Just don't understand why someone would come to an alternative thread and discourage anyone. Is there no safe place to discuss this subject on the forum?

Ruby3813

dtad - I sent you a private message. Thx, Ruby

Anonymous

In answer to the original poster's query---I do know that if you want to keep estrogen from circulating in your body, you MUST avoid alcohol like the plague. So if you want to avoid an AI but still protect yourself from a recurrence, stay away from alcohol. Don't buy into that "red wine" argument, since the benefits from red wine can be found in other foods.

Exercise-- and not just strolling through the park--keeps our weight down, and since more weight gain gives estrogen more places to "hang out", so to speak, that's an important factor too. Plant-based diets and low-fat food choices appear to help. The following journal article is pretty "science-y" but has some good infor.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC51122...

Finally, drink your coffee or tea. This article talks about using caffeine in tamoxifen-tx'd women, but it seems to have a preventative effect without it. "..The team found that both of these compounds - particularly caffeine - reduced cell division and increased cell death among both ER+ and estrogen receptor-negative (ER-) breast cancer cells."

http://www.medicalnewstoday.com/articles/292879.ph...

Claire in AZ

Kristiina

I find this topic interesting. I have the same question....my percentage is just a little higher. 7% improvement. So far I am taking letrazole with negligible side effects. My concern is my bone health. I had my first bone scan just before I was diagnosed as having breast cancer and I fell in the osteopenia range. It scares me to be taking medicine That could contribute to this problem. How do you weigh future bone strength against a 7% prevention rate.

dtad

Hi everyone...I'm sure I posted something originally. However now that the thread has become active again I just want to say that I refused an aromatase inhibitor form the start. I'm almost 3 years NED. So far so good. I do realize there are no guarantees either way. Good luck to all.

Bosombuddy101

Breast cancer recurrence is highest during the first two years and it's a well known fact that recurrence risk decreases over time, even for patients who have opted out of endocrine therapy. Survival curves are not linear over time Despite the negligible benefits provided by aromatase inhibitors for node negative early stage breast cancer, what is lacking in these studies is the long-term effects of aromatase inhibitors on overall health and the associated cause of death from taking this medication. Unfortunately, this large scale study is still ongoing.

BarredOwl

Each must come to their own decision about what is right for them, in light of their personal risk tolerance. However, having accurate information is an element of informed decision-making. Regarding the use of "surrogate" endpoints referenced above, in the setting of early stage invasive breast breast cancer, mortality has been assessed and benefits in terms of overall survival and/or breast cancer-specific survival have been shown. For a more detailed explanation with citations to selected clinical trial publications, see this recent post.

As I explained earlier in this thread in more detail, because benefit is proportional to individual risk, I agree that the relative risk reductions observed and the absolute benefits reported in certain clinical trials are not as relevant to decision-making as case-specific estimates of recurrence risk and/or mortality risk, and the related absolute potential benefits provided by one's medical oncologist.

The statement above referring to "the negligible benefits provided by aromatase inhibitors for node negative early stage breast cancer" is somewhat misleading, because such patients have varying recurrence risk profiles and the benefits of Tamoxifen and AIs are proportional to risk and thus may vary quite a bit. Even patients with identical tumor histology, tumor size, nodal status, ER status, PR status, HER2 status, and grade may not be similarly situated with respect to risk and potential benefit. For example, due to differences in tumor biology, distant recurrence risk profile (and the potential benefit of endocrine therapy in reducing distant recurrence risk) may differ materially. Lastly, the exact same benefit may be viewed differently by different patients, due to differences in risk tolerance.

BarredOwl

Bosombuddy101

BarredOwl,

I was merely referencing the studies to the links you provided which looked at the benefits of endocrine treatment and associated risks in the context of toxicities. The toxicities of these drugs should not be ignored—surely this is a big factor in the risk benefit analysis to treatment? With respect to risks you mention only the risk profile of the tumor. That is not entirely an accurate statement since this is not the only risk in the treatment equation. The period under study for the ATAC trial was only 10 years and these women got other cancers, life threatening thrombotic events, osteoporosis etc.. This isn't something that should be glossed over for early stage node negative breast cancer! What is the incidence of these cancers in the general population and to what extent do these drugs contribute to other cancers or adverse events over the long term? These questions can't be answered because the studies are still ongoing.

Excerpt from ATAC Trial:

ATAC (10-year analysis): (Ana) versus (Tam) versus (Tam + Ana);

Cuzick (2010): http://thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract

Doctors assessed the long-term outcomes after a median follow-up of 120 months.

Methods

We used a proportional hazards model to assess the primary endpoint of disease-free survival, and the secondary endpoints of time to recurrence, time to distant recurrence, incidence of new contralateral breast cancer, overall survival, and death with or without recurrence in all randomised patients (anastrozole n=3125, tamoxifen n=3116) and hormone-receptor-positive patients (anastrozole n=2618, tamoxifen n=2598). After treatment completion, we continued to collect data on fractures and serious adverse events in a masked fashion (safety population: anastrozole n=3092, tamoxifen n=3094).

Fractures were more frequent during active treatment in patients receiving anastrozole than those receiving tamoxifen (451 vs 351; OR 133, 95% CI 115–155; p<00001), but were similar in the post-treatment follow-up period (110 vs 112; OR 098, 95% CI 074–130; p=09). Treatment-related serious adverse events were less common in the anastrozole group than the tamoxifen group (223 anastrozole vs 369 tamoxifen; OR 057, 95% CI 048–069; p<00001), but were similar after treatment completion (66 vs 78; OR 084, 95% CI 060–119; p=03). No differences in non-breast cancer causes of death were apparent and the incidence of other cancers was similar between groups (425 vs 431) and continue to be higher with anastrozole for colorectal (66 vs 44) and lung cancer (51 vs 34), and lower for endometrial cancer (six vs 24), melanoma (eight vs 19), and ovarian cancer (17 vs 28).

BarredOwl

My point was that "node negative early breast cancer" includes patients with differing risk profiles, and therefore differing benefit and the benefit is not "negliglible" in all such patients, despite your assertion to the contrary. The plain language of the first clause of your sentence was an assertion of "negligible benefit" in a specific patient population:

"Despite the negligible benefits provided by aromatase inhibitors for node negative early stage breast cancer. . . "

The word "negligible" indicates a puny or insignificant amount. "Benefit" is a fixed estimate and the amount of benefit does not change in quantity when weighed against the risks of treatment (side effects).

Absent an express limitation to a particular subset, "early stage invasive breast cancer" generally includes Stages IA to IIIA. You can see that "node-negative" early breast cancer includes a variety of stages:

Specifically, "node-negative" early breast cancer includes:

Stage IA (T1 N0, M0)

Stage IIA (T2 N0 M0)

Stage IIB (T3 N0 M0)

A "T2"-size tumor is Tumor >20 mm but ≤50 mm (5 cms) in greatest dimension.

A "T3"-size tumor is Tumor >50 mm (5 cms) in greatest dimension.

To suggest that all such node-negative patients derive "negligible benefit" from endocrine therapy is simply not true. (Again, whether the potential benefit sufficiently outweighs the potential risks in the patient's view is a separate question, but that does not change the size of the estimated benefit.)

Those familiar with my history of posting know that I am not a proponent of treatment without regard to the associated risks. As I recently wrote in the conventional forum: "Ideally, new members would receive a balanced, representative, complete and accurate picture of the potential benefits and the potential risks of treatment, preferably evidence-based. . ."

I did not ignore them in this thread either. In my last post, although I did not repeat the full content of my earlier post, I did link back to it. Indeed, the article you are quoting from (along with my personally crafted descriptor "ATAC (10-year analysis): (Ana) versus (Tam) versus (Tam + Ana)") is one of three "Additional Miscellaneous References" that I provided above in that linked post from this thread. In that same post in this thread, I also explained (bold in original above):

=====> Because potential benefit is proportional to individual risk, patients should always seek case-specific advice from their medical oncologist regarding their estimated recurrence risk(s) after all other treatments, the potential relative risk reduction benefit and estimated absolute risk reduction benefit(s) of any proposed endocrine therapy regimen (versus no treatment) in their particular case. This in turn is weighed against the risks of treatment in a personalized risk/benefit analysis.

Note the last sentence: "This in turn is weighed against the risks of treatment in a personalized risk/benefit analysis." Risks of treatment refers to the side effects of the drugs.

Regarding other cancers, the ATAC trial was comparing the AI to Tamoxifen. The incidence of second non-breast cancer causes of death has been separately assessed in studies of Tamoxifen versus placebo in breast cancer patients. (The general population is not considered to be the appropriate comparator population, because those diagnosed with breast cancer have a different risk profile from general population (are at increased risks of certain types of cancers)).

While the ATAC trial publication linked above was published seven years ago in 2010, with a median follow-up period of 10-years (120 months), there is a more recent update available in this 2017 abstract: "Long-term comparison of anastrozole versus tamoxifen: Results from LATTE/ATAC".

[Edit: I would add that it is not necessary to downplay the potential benefit or to posit negligible benefit to support a decision to decline treatment, given that potential benefits are weighed against the potential risks, in light of all applicable clinical and pathologic factors (e.g., age, life-expectancy, personal medical (e.g., co-morbidities) and family history that may affect susceptibility to severe adverse effects), as well as individual risk tolerance (e.g., different views about whether the potential benefits (of whatever size) are seen to sufficiently exceed the potential risks to be worth it to the individual in question).]

BarredOwl

[Later edit: Correction of "T2" to "T3", such that a typo in "Stage IIB (T2 N0 M0)" was corrected to read "Stage IIB (T3 N0 M0)" per the Table. In view of the correction of "T2" to "T3", also added the definition of "T3" (A "T3"-size tumor is Tumor >50 mm (5 cms) in greatest dimension.)]

Bosombuddy101

BarredOwl,

I appreciate everything you do. Thank-you so much for providing these links because they are so very informative for me personally and I'm sure for many other readers. It's very easy to get lost in the sea of studies on pubmed.