Recurrence after refusing hormone therapy?

Just try it... I'm on month 4 and absolutely NOTHING has changed. I have no side effects, and I'm a certified Ultra Rapid Metabolizer of Tamox - so SEs would be greater for me. Honestly, it's like a daily sugar pill. You should try it, especially if you have children to live for. I haven't gained weight, feel totally me, and it's nice to know this pill is protecting me - even a little bit.

After talking to hundreds of breast cancer patients, I'm of the school to GIVE Tamoxifen or Aromatase Inhibitors a try.

I've talked to many women who have had recurrences and they either quit Tamoxifen or never started it. They very much regret their decisions to not try (or that they stopped) the drug.

Many women have very few side effects. I remember letting the Arimidex prescription I had sit for awhile as I was terrified to take it. Now, 4 years into it, I thank God every day before I take it. And when I pick up the script at the drug store, I am filled with gratitude that there is such medication.

Good luck to you and your decision.

Jul1970. I hear exactly what you are saying. I was 47 at the time and my oncologist told me that the benefit of taking the Tamoxifen was very small. I looked at possible side effects and asked him if I would be okay without it. He told me to go live a long, healthy life and didn't need to see him again. I had my double mastectomy in August 2015 and underwent reconstruction. I basically lived as if the BC was but a blip on my radar. Until I saw my breast surgeon and she was shocked I wasn't on the Tamoxifen. I told her about what the MO said. His report didn't reflect that advice, however, and he reported that I didn't need chemo, but Tamoxifen was on the table. I was shocked. My oncotype dx score was also 8. I even got a nifty Adjuvant for BC print out that gave a 1% benefit for taking Tamoxifen. Cancermath.net went further and after plugging in my stats, it basically said there was NO benefit to hormonal therapy. My surgeon disagreed with my MO and highly suggested I do more research and get a 2nd opinion. After doing more research, I'm just more confused. What good is the oncotype dx test when it comes to hormonal therapy then? I certainly don't want to play with fire and don't want to be negligent, but I also do not want to take a drug that may not provide me with any benefit other than simply because it is "standard of care." I've read Dr. Susan Love's article in the Huffington Post about how all invasive cancer is metastatic cancer. But again, isn't that what the oncotype testing is for? Do you think it lulls some of us into a false sense of security? I'm really curious, on an overall scale, how accurate their reports are- what is their margin for error? Ultimately, I am getting a 2nd opinion in November. I'm hoping this new MO can clear up some of the grey area with this issue.

The following comments relate to the OncotypeDX test for invasive disease, and the content of the node-negative ("N0") reports.

Re: "What good is the oncotype dx test when it comes to hormonal therapy then?"

Older clinical trials established the benefit of endocrine therapy in ER+ patients, and these clinical trials showed that the potential risk reduction benefit of tamoxifen is ~ 45%. (The potential risk reduction benefit depends on the size of the baseline risk). For clinicians, the question is not whether to prescribe endocrine therapy, but whether chemotherapy should be added to endocrine therapy. The OncotypeDX test for invasive disease was designed to assist with this question: whether to add chemotherapy to endocrine therapy or to rely upon endocrine therapy alone.

The recurrence risk information in the node-negative Oncotype report is based on clinical trials in which all of the patients received endocrine therapy with tamoxifen (either tamoxifen alone or tamoxifen plus chemotherapy). Thus, if a patient declines endocrine therapy, the average 10-year risk of distant (metastatic) recurrence would be substantially higher than shown in their Oncotype test report. (This is what members here mean when they say that the "test assumes" receipt of 5-years of endocrine therapy.)

Unfortunately, the test report does not include an estimate of recurrence risk without endocrine therapy. However, one's Medical Oncologist ("MO") can provide an independent estimate (e.g., based on the established potential risk reduction benefit of 45% associated with tamoxifen).

The Onctoype test result is based on the biology of your tumor (the mRNA expression levels from 16 cancer-related genes) and provides information beyond standard clinico-pathologic factors alone, such as those used in the lifemath calculator. This is especially true for node-negative tumors with Recurrence Scores of 0 to 10, for which strong prospective data is available from the TAILORx trial. In this trial, the patients scoring 0 to 10 were assigned to receive endocrine therapy alone, and the impressive outcomes at five years are with endocrine therapy (e.g., tamoxifen, an aromatase inhibitor).

TAILORx trial (full-text page): http://www.nejm.org/doi/full/10.1056/NEJMoa1510764#t=article

Supplementary materials are available at the full-text page.

PDF version of article: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510764

"Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease–free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local–regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6)."

Please ask your current medical oncologist (or second opinion MO) whether in your particular case, you should be considering recurrence risk information from on-line calculators (which are broad population-based statistics according to clinico-pathologic features), or whether the average 10-year distant ("metastatic") recurrence information from your Oncotype report is likely to provide a more tailored estimate of distant recurrence risk for you.

If you seek a second opinion, be sure to ask for an explanation of how your recurrence risk without endocrine therapy is being estimated. Be sure to inquire what the incidence of severe adverse events is (in light of your personal medical and family history), so that you can compare the potential risk reduction benefit of adding endocrine therapy against the associated risk of potential severe adverse events.

I am a layperson with no medical training. All information above should be confirmed with your medical oncologist to ensure receipt of accurate, current, case-specific expert professional medical advice.

BarredOwl

Thank you BarredOwl! I will read the TAILORx article you referenced. I appreciate all the information you provided.

I will also encourage you to at least try Tamoxifen; as others have said, you can always stop, or even take a "holiday", if the SEs become too much. I tried Tamoxifen for 3 months and found the SEs difficult so I stopped, then started again, and finally gave up. But - I tried, twice, and have no long-term SEs from it. I had to be sure, before I stopped, that if I had a recurrence I wouldn't blame myself for stopping. If you choose not to take it, or try it and stop (both legitimate choices), be certain you won't have any regrets down the road.

Regarding the metabolism comments above, there has been some confusion in the threads stemming from misunderstanding of the distinction between a drug that is the "active per se" versus a drug that is a "pro-drug" (which is metabolized to produce the active(s)). This affects the appropriate dose adjustments in opposite directions.

Tamoxifen is a "pro-drug". Accordingly, in theory, the dose adjustment considered for a known CYP2D6 poor metabolizer would be a dose increase.

Some drugs have well-established dose-adjustment guidance based on studies that establish the safety and the efficacy of dose adjustments in case of less active or overactive metabolism, and the dose adjustments are included in the FDA label. For other drugs, such as tamoxifen and the enzyme CYP2D6, various studies are conflicting, and in my personal opinion, the picture is still evolving.

The following is provided for information only.

Pharmocogenetic Testing and Different Dose Adjustments for an "Active" versus a "Pro-drug":

If genetic test results indicate a metabolic enzyme is more or less active, and you know the enzyme handles the metabolism of a particular drug, you can consider adjusting drug dose to optimize activity or reduce side effects. However, for the same metabolic enzyme, with different drugs, the correct dose adjustment (increase or decrease) may not be the same. This is because some drugs are the "active" themselves, while other drugs are "prodrugs" that are converted to active metabolites.

Consider the following regarding Enzyme X and possible dose adjustments for Drug A (the active) versus Drug P (a prodrug).

(1) One example would be a DRUG A that is the "active per se". Metabolism of DRUG A via ENZYME X reduces the amount of the active substance, producing inactive or less active metabolites.

(1a) In an ENZYME X ultra-metabolizer, the active DRUG A would be rapidly converted to inactive or less active metabolites (potentially reducing activity). A dose increase might be considered to increase the level of DRUG A.

(1b) Conversely, in an ENZYME X poor metabolizer, the active DRUG A would persist in the patient (potentially increasing activity and side effects). A dose reduction might be considered to reduce the level of DRUG A.

(2) Another example is DRUG P that is a "pro-drug". Metabolism of DRUG P (a pro-drug) via ENZYME X increases the amount of active metabolite M.

(2a) In an ENZYME X ultra-metabolizer, the pro-drug DRUG P would be rapidly converted to the active metabolite M (potentially increasing activity and side effects). A dose reduction might be considered to reduce the level of active metabolite M.

(2b) Conversely, in an ENZYME X poor metabolizer, the pro-drug DRUG P would not be converted efficiently to metabolite M (potentially decreasing activity). A dose increase might be considered to increase the level of the metabolite M.

As you can see, for a specific change in Enzyme X, the dose adjustments would be the opposite for Drug A versus Drug P (compare in an ultrametabolizer (1a) versus (2a); compare in a poor metabolizer (1b) versus (2b)).

Each drug must be considered separately, and many factors must be considered for each drug taken. Such factors include the evidence (if any) regarding the activity of each specific drug and its various metabolites; the effect (if known) of possible dose adjustments up or down upon active metabolite(s); the clinical data available (if any) regarding the therapeutic efficacy of particular adjusted doses; and the long-term safety of such adjusted doses. For each drug, the FDA label should be checked for any pertinent information. In addition, patients must consult with a medical professional regarding whether any proposed dose adjustment is known to be safe and effective, and/or whether an alternative drug should be considered.

Patients should never alter the dose of a prescription drug without first consulting with their medical oncologist.

BarredOwl

Yes, all wise words of wisdom. I feel very blindsided since it was my MO who basically told me the "benefit" from Tamoxifen was negligible for me. Of course I took those words and ran with them! I should have done more research at that time. But I swear, between everyone acting like "well, you had the cancer removed" so now your CURED! and my MO telling me go live a long healthy happy life - I bought into it with gusto! Live and learn. I won't return to him but do have the 2nd opinion in November. Thank you ladies

barbe, I would hope for more than that for you! I was stage IV from the get go in 2010 and I took anastrozole (generic arimidex) and it worked for 5 years before progression! May it work as good, or better for you!

Diane

Barbe1958 and DC197 - thank you for posting. That is so informative to know the power of these drugs.

Barb and DC thank you so much for posting. It reiterates why I need to take my little white pill each and every day and what a good job it is doing in the background. I still wonder why they take us off it after 10 years and we don't stay on it for life, even at a small dose when we are old with shriveled ovaries:)

I think there might be few stats about breast cancer patients NOT taking hormonal therapy vs breast cancer patients who DO take hormonal therapy, simply because running such multi-year study on women with invasive cancer would be unethical to the women in the group NOT taking hormonal therapy. So all the stats if available are probably coming from database searches and comparison to much older studies. Tamox has been around for over thirty years if I am not mistaken.

Editing to add link to a study that might provide some answers to the OP's question: Efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.

My sister had a lumpectomy with chemo and radiation. She tried tamoxifen for a couple of months and quit due to side effects. That was over 12 years ago and she is still free of disease. I just had double mastectomy with reconstruction in July. Since my sister and niece had breast cancer, I underwent genetic testing and found that I cannot tolerate radiation therapy (ATM gene), so did not have that and Oncotype indicated no chemo was indicated. However, OM ordered arimidex which I took for a short time and quit due to SE. Starting femara today and hoping for better luck with it. At least I gotta try.