HRT and Breast Cancer

Since the year 2002, the General Consensus about Estrogen is:

  • It drives cancer

  • Avoid it as much as possible

  • If absolutely necessary, use the lowest dose for the shortest period of time

  • It drives dementia

  • It drives aging

And all of this stemmed from a study called the Women’s’ Health Initiative, aka the “WHI”.

Let’s dive into how this estrogen mistrust came about . . .

The Women’s Health Initiative/WHI

This was a study funded by the NIH from 1993 to 1998. 27,000 post menopausal women, aged 50-79 years with no prior breast cancer history were enrolled in one of two randomized, placebo-controlled trials.

Women with an intact uterus were given 0.625 mg/day of CEE (conjugated equine estrogen) and 2.5 mg/dayMPA (medroxyprogesterone, a progestin) or a placebo pill.

Women with a prior hysterectomy were given CEE alone or placebo.

The study was stopped prematurely at 5 years.

The study findings were published in 2002, though the participants continued to be tracked until December, 2019 (more on this later).

The entire goal of the study was to hopefully find data points to show how beneficial hormone replacement was and how we could protect Medicare from tanking.

Although the data was originally misinterpreted to the public to say that HRT (hormone replacement therapy) increased the risk of breast cancer, subsequent study showed it was actually the CEE + MPA arm only that showed an insignificant increase in the risk of breast cancer.

However, by then, the fear had spread far and wide. Women no longer trusted HRT (especially estrogen). Doctors were fearful of getting sued. The FDA put a warming label on all estrogen products.

Early pioneers like Dr. Leon Sperrof wrote multiple studies urging physician to not let a singular randomized trial stop was decades of clinical outcomes had shown brain, breast, gut, bone, cardiovascular, mitochondrial, and mental health protection.

The WHI Re-Analysis:

December 2019 at the San Antonio yearly breast cancer symposium, Dr. Rowan Chlebowski presented “remarkable” new data on menopausal hormone therapy.

After 19 years of follow-up, here were the findings:

  • CEE  alone resulted in a  23% reduction in breast cancer

  • CEE+MPA resulted in a 29% increased risk of breast cancer

  • In terms of deaths from breast cancer: A significant 44% reduction with CEE alone, and these effects continue for up to 20 years!

No existing agent meant for breast cancer risk reduction has been able to demonstrate a reduction in deaths from breast cancer so this is a very unique finding.

See his abstract here: https://aacrjournals.org/cancerres/article/80/4_Supplement/GS5-00/645966/Abstract-GS5-00-Long-term-influence-of-estrogen

Have you Heard about this?

This 19-year re-analysis did not make headlines. Most doctors haven't heard about this. Most pharmacists haven’t heard about this. Most patients haven’t heard about this.

Fear sells headlines (even back in 2002), but positive data does not.

More Data

The Fred Hutchinson Cancer Research Center at the University of Washington reviewed records of 2,755 women diagnosed with cancer between 1977 and 1999.

HRT given to breast cancer survivors had no adverse effect on recurrence or mortality.

In fact, breast cancer survivors on HRT had significantly lower breast cancer recurrence rates, breast cancer mortality rates, and overall mortality rates compared to survivors not on hormones.

J Natl Cancer Inst. 2001 May 16; 93(10):754-62. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality.

“Women diagnosed with breast cancer while on hormonal or estrogen therapies have consistently been found to have better prognoses than women diagnosed without being on hormonal therapies.”

Avrum Bluming MD, Carol Tavris PhD.Estrogen Matters: Why Taking Hormones in Menopause Can Improve Women’s Well-Being and Lengthen Their Lives -- Without Raising the Risk of Breast Cancer 1st Edition. Hachett Book Group 2018. Page 10.

And This

Did you know that the use of high-dose estrogen, which began in the 1940s, was the first successful breast cancer therapy?

If estrogen were “carcinogenic”, this would not have worked

Using oral estrogens to treat breast cancer continued all the way into the late 1970s, until Tamoxifen (selective estrogen receptor modulator or SERM, an anti-estrogen) was introduced. When Tamoxifen became the standard of care in 1974, estrogen therapy pretty much stopped.

As women get older and are “less” estrogenized, their risk of breast cancer goes up. Pregnancy, a time of hormones elevated up to 10-fold, offers a risk reduction of breast cancer. Nuns who never get pregnant have been studied and shown to have a higher lifetime risk of getting breast cancer.

Something else about that dang WHI study . . .

In the WHI, there was an unusually low incidence of breast cancer in the placebo group. A little known tidbit is that 25% of the placebo participants had previously been on CEE - they were part of a “washout” group, which is therapy discontinuation for a given period of time prior to the study.

Instead of wondering "why do the placebo folks have such a low rate of breast cancer?" which they would have learned was due to previous use of CEE (go figure!) - they jumped to the conclusion that the treatment arm was the culprit. A re-look at the data says that the CEE +MPA group had the same risk of breast cancer when compared to those who had never used hormone therapy.

It was only because the “washout” placebo group went into the study with a lower risk of breast cancer than average (due to previous use of CEE) did the CEE + MPA group seem to have a “higher” risk of breast cancer.

Estrogen Receptor Positive Breast Cancer:

Many doctors and women think estrogen receptor positive (ER+) breast cancer cells (having estrogen receptors on the tumors) means estrogen is “feeding’ or “driving” the cancer.

But a close look at the science shows this is most often not the case

Estrogen receptors are found on all normal breast cells. Estrogen receptors on tumor cells signifies that the tumor is growing so slowly that the breast cell still has some normal cellular characteristics.

Scientific biological studies are revealing cells that initiate tumor growth and recurrence, called cancer “stem” cells , or “cancer initiating cells”,  do not have estrogen receptors, nor do they proliferate (grow) in response to estrogen.

Estrogen should be Celebrated, not Feared

  • Estrogen protects mitochondria from damage

  • Estrogen “allows” histone changes of epigenetics

  • Estrogen maintains the volume of the brain’s hippocampus providing memories and motivation

  • Unoccupied estrogen receptors can combine with inflammatory cytokines

  • Estrogen helps the liver to detoxify

  • Estrogen protects breast tissue

And so.much.more.

💕

Dr. Laura Neville

 

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