Question: My 46 year old wife had stage 1A invasive ductal breast cancer (low grade) around 4-5 years ago, and is still currently on daily Tamoxifen. When she was initially diagnosed, she had a bilateral mastectomy, negative lymph nodes (she had radiation but no chemotherapy). Her cancer was found to be estrogen positive (ER+). She is BRCA-. She even had an Oncotype DX and a Mammaprint Test, both which stated low risk.

Her last physical exam by her doctor a few months ago was unremarkable. She had routine blood tests which were all normal except her serum estrogen level was very high, 797 pg/mL. I am pasting her serum estrogen result: 797 pg/mL .

FOR REFERENCE SERUM ESTROGEN:
Prepubertal <40
Female Cycle:
1-10 Days 61 - 394
11-20 Days 122 - 437
21-30 Days 156 - 350
Post-Menopausal <40
HMG Treatment for Ovulation
Induction: 400 - 800

Her tumor markers CA 15-3 (breast cancer tumor marker) and CA-125 (ovarian cancer tumor marker) and other labs including C-reactive protein and sedimentation rate, WBC, etc were all completely normal. We have never tested her serum estrogen level before, but it was actually accidentally ordered, and it is very elevated.

My question is: Why is the serum estrogen level so high? Is it the result of the Tamoxifen? And if so, does this indicate that the Tamoxifen isn't working anymore or isn't effective (ie. developed resistance)?
In your opinion, is she at higher risk of a recurrence? What are your suggestions?
Additional information for you is that she is not menopausal, she is 46 years old, so she is not eligible to take medications such as Arimidex. Basically, should we be worried about these results, and what should we do going forward? Thank you

First of all, I'd like to thank you for your great response. I read about gonadotropin releasing hormone agonist, and it has many side effects. Do you think this is very necessary, or simply a precautionary suggestion? I agree with you, that once she is "menopausal" she should switch to Arimidex.

With regards to her high serum estrogen level, you said this high level could be attributed to her being "premenopausal/perimenopausal"? But isn't her level still very very high, even for that? Or do you think it could still be within normal range, given the fact she is on tamoxifen. When I googled this, some papers state that high serum estrogen levels may be indicative of Tamoxifen resistance. Do you agree with this, or is this not really common consensus?

Bottom line, you don't think I should be too worried, right? What if she simply just continued doing what she's doing now (ie. daily Tamoxifen, routine 6 months doctor checkups, annual lab test), and not change anything, would that also be reasonable? Thank you Dr. Sundriyal.