Estrogen receptor positive (ER+) breast cancer is the most common type of cancer affecting women worldwide and accounts for more than 80% of all breast cancer diagnoses worldwide. It is also the most common breast cancer type in males, though males rarely get breast cancer. The standard of care therapy for such types of cancer is the administration of a an estrogen blocker such as tamoxifen or clomiphene, often in combination with an aromatase inhibitor (AI). However, the estrogen blockers are not true anti-estrogens and are in fact officially known as selective estrogen receptor modulators (SERM), since they have potent estrogenic effects in many tissues despite having (partially) anti-estrogenic effects in breast tissue. These SERM drugs are actually synthetic non-steroidal estrogens, which have been modified slightly to achieve their selective (and partial) estrogen blocking effects in some tissues. As a result of this cunning partial estrogenicity, the response to SERM therapy is an abysmally low ~30%, which can be raised to 50%-60% when combined with an AI drug. Interestingly enough, therapy by AI drug alone, especially with steroidal AI drugs such as exemestane, can be as high as 80%, which further corroborates the dangers of SERM drugs. However, SERMs remain first line of therapy for most women with ER+ breast cancer and are unlikely to be replaced any time soon. The study below reports the stunning findings that adding progesterone to tamoxifen therapy not only completely blocked tumor growth after just 4-5 weeks of treatment, but actually started to induce tumor regression in subsequent weeks. This finding is the exact opposite of current medical recommendations, which state that progesterone therapy should be avoided since it can both cause breast cancer de-novo and promote the growth of already established tumors. In fact, states such as California have mandatory warning label requirements on any product sold in California that contains progesterone. The real kicker to the study below is that progesterone was found to be therapeutic even in progesterone receptor positive (PR+) breast tumors – the very tumor type progesterone is supposed to cause/stimulate!
In terms of practical takeaways, the progesterone dose was not even that high. The human-equivalent doses was 0.6mg/kg daily, which means for most people 50mg-60mg progesterone daily should do the trick. When progesterone is dissolved in tocopherols and taken orally it has systemic bioavailability of about 60%-70%, which means a daily dose of about 100mg should be enough to replicate the study. While the study is politically correct and says that progesterone worked by enhancing the anti-estrogenic effects of tamoxifen, the real story is that progesterone simply blocked the partial estrogenic effects of tamoxifen. As such, an possibly optimal hormonal treatment of ER+ breast cancer may be a combination of a true anti-estrogen such as progesterone and a steroidal AI such as exemestane.
http://dx.doi.org/10.1038/nature14583
https://www.cancernetwork.com/view/uncovering-role-progesterone-treatment-breast-cancer
“…In a landmark study, Cambridge University researchers have shown that progesterone – an inexpensive drug used in contraceptives – slows the growth of tumours. In lab tests, it made tamoxifen, the gold standard breast cancer medicine, work twice as well as usual. As a result, experts believe it could be a life-saver. The journal Nature said it was ‘time to rethink breast cancer’. Researcher Jason Carroll said: ‘The results are pretty clear and potentially have direct benefits for many women with breast cancer.’ Dr Carroll’s research centres on tumours that are fuelled by the hormone oestrogen. Some of these are also sensitive to progesterone, a hormone used in contraception. Dr Carroll, who is funded by Cancer Research UK, showed that…progesterone ‘talks’ to the oestrogen that is trying to feed the tumour. This stops the cancer from growing as quickly. In tests on mice with tumours, giving progesterone at the same time as tamoxifen, a drug widely used to stop breast cancer coming back after surgery, had a dramatic effect.”
