Antiestrogen withdrawal response explained

The antiestrogen withdrawal response is a paradoxical improvement in breast cancer caused by discontinuation of antiestrogen therapy for breast cancer.^{[1] [2] [3] [4] [5]} It has been documented rarely with the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. The phenomenon indicates that these agents can somehow result in stimulation of breast cancer tumor progression under certain circumstances. One proposed theory for the mechanism is that the sensitivity of breast cells to estrogens shifts with estrogen deprivation, and upon antiestrogen withdrawal, endogenous estrogen acts in the manner of high-dose estrogen therapy in the breast to inhibit breast cancer growth and induce breast cancer cell death. The antiestrogen withdrawal syndrome is analogous to but less common and well-known than the antiandrogen withdrawal syndrome, a phenomenon in which paradoxical improvement in prostate cancer occurs upon discontinuation of antiandrogen therapy.

Notes and References

1. Jordan VC . A Raloxifene Withdrawal Response: Translational Research, Definitions, and Clinical Applications . Integr Cancer Ther . 15 . 3 . 242–4 . September 2016 . 27271771 . 5739192 . 10.1177/1534735416651329 .
2. Dosik M, Kaufman R . Raloxifene rebound regression . Cancer Invest. . 22 . 5 . 718–22 . 2004 . 15581053 . 10.1081/cnv-200032978 . 23443457 .
3. Lemmo W . Anti-Estrogen Withdrawal Effect With Raloxifene? A Case Report . Integr Cancer Ther . 15 . 3 . 245–9 . September 2016 . 27411856 . 5739193 . 10.1177/1534735416658954 .
4. Maximov PY, Abderrahman B, Curpan RF, Hawsawi YM, Fan P, Jordan VC . A unifying biology of sex steroid-induced apoptosis in prostate and breast cancers . Endocr. Relat. Cancer . 25 . 2 . R83–R113 . February 2018 . 29162647 . 5771961 . 10.1530/ERC-17-0416 .
5. Ariazi EA, Ariazi JL, Cordera F, Jordan VC . Estrogen receptors as therapeutic targets in breast cancer . Curr Top Med Chem . 6 . 3 . 181–202 . 2006 . 16515478 . 10.2174/156802606776173474 .