Thanks to social media, confusion surrounding Hormone Replacement Therapy (HRT) has only increased.
To clear things up, I sat down with Dr. Kristi Funk, MD—a board-certified breast cancer surgeon, bestselling author, and dedicated women’s health advocate.
Dr. Funk graduated with distinction from Stanford University, completed her general surgery residency in Seattle, and a breast fellowship in Los Angeles. She has guided thousands of women through breast health decisions, including well-known figures like Angelina Jolie and Sheryl Crow.
There is no one better I can think of to shed light on HRT and breast cancer risks!
This information is for educational purposes only and at the time of writing in Jan 2025. You should not rely on this information as a substitute for medical advice, diagnosis, or treatment. If you have a question about your health, supplements, or medications, please consult with your own healthcare provider.
Let’s dive in!
1. Does HRT increase your risk of breast cancer?
As unpopular as this answer might be among those who strongly support the use of HRT in all circumstances, the answer is, “Yes, HRT increases the risk of breast cancer.” But don’t panic - let’s unpack this.
The increase in risk is relatively small, and when breast cancer does occur with HRT use, it tends to be less aggressive.
Breast cancer risk
In 1997, before the Women’s Health Initiative ‘Earthquake’ which shook the HRT world, 21 of the world's biggest names in breast cancer research came together and published a meta-analysis in The Lancet (a very prestigious journal). They took data from 51 studies, covering 90% of the worldwide epidemiological evidence available at the time. The findings were as follows:
For women aged 50 to 70 who never use HRT, the risk of developing breast cancer is 45 per 1,000 women. If HRT is started at age 50:
After 5 years of HRT use, the risk increases by 2 cases (to 47 per 1,000 women).
After 10 years, the risk increases by 6 cases (to 51 per 1,000 women).
After 15 years, the risk increases by 12 cases (to 57 per 1,000 women).
The effect of HRT on mortality (deaths from breast cancer) was not clear; however, cancers diagnosed in women who had ever used HRT tended to be less advanced than those diagnosed in never-users. Interestingly, breast cancer risk was higher in women on HRT who were normal weight as compared to overweight women. This makes physiologic sense because women who are overweight or obese already live with elevated levels of circulating estrogen, so the bump in estrogen levels from HRT carries no additional impact on breast cancer risk.
It’s important to differentiate GETTING breast cancer from DYING from it.
While HRT slightly raises the chance of developing breast cancer, the cancers associated with HRT tend to be less advanced and more treatable. This was highlighted in a 2016 Finnish study involving 489,105 women using HRT. During the study, 1,578 women died from breast cancer. Compared to the general population, the risk of death from breast cancer was reduced by 40-50% for women using HRT, regardless of the type, duration of use, or age at diagnosis. The greatest reduction in mortality was seen in women aged 50-59, where the risk dropped by 67%.
To put this in perspective:
If the baseline risk of dying from breast cancer is 1 in 10 women, HRT use reduces this to 1 in 20 women — a 50% reduction.
In Summary
While HRT does increase the risk of breast cancer, it does so infrequently, and the resulting cancers are generally less aggressive and more curable.
2. Is HRT contraindicated in women with ‘dense’ breasts?
Contraindicated? Definitely not.
Riskier? Yes, taking HRT with dense breasts is riskier compared to taking it with fatty breasts.
The issue is twofold:
Estrogen and progesterone increase breast density. Studies show that taking tamoxifen, an estrogen blocker, decreases breast density.
Increased breast density elevates cancer risk and complicates detection. Higher breast density is associated with an increased risk of developing breast cancer AND makes it harder to detect cancer through screening mammograms. Since both dense tissue and cancer appear white on a mammogram, finding cancer becomes like searching for a snowball in a snowstorm.
How Bad Is the Detection Issue?
In women with “heterogeneously dense” breasts: 25% of cancers are missed on mammograms.
In women with “extremely dense” breasts: 40% of cancers are missed.
How Common are ‘dense breasts’?
50% of women under 50 have dense breasts.
40% of women in their 50s have dense breasts.
30% of women over 60 have dense breasts.
When you take HRT, you maintain breast density and the associated elevated risks that come with it.
Does it make breasts denser?
Both estrogen and progesterone independently and/or combined together increase breast density.
3. Does HRT increase your risk of other estrogen-dependent cancers?
Uterine (Endometrial) Cancer
Estrogen replacement alone increases the risk of uterine cancer. However, if you still have a uterus, you can completely offset this risk by taking progesterone alongside estrogen.
Ovarian Cancer
In 2015, the Collaborative Group on Epidemiological Studies of Ovarian Cancer published a meta-analysis of 52 epidemiological studies. They concluded that HRT does increase ovarian cancer risk, but the increase is quite small.1 Specifically:
Using HRT for 5 years starting around age 50 results in:
1 additional ovarian cancer case per 1000 users
1 additional ovarian cancer death per 1700 users (assuming a typical prognosis)
4. Can you take HRT if you have the BRCA gene mutation?
Yes, BRCA mutation carriers can and often should take HRT. When a BRCA patient (actually, any woman) has her ovaries surgically removed prior to natural menopause, she becomes at risk for osteoporosis, subsequent bone fractures, muscular atrophy, compromised cardiovascular and brain health, early mortality, and of course, all of the well-known menopause pleasantries, including but not limited to hot flashes, night sweats, insomnia, mood swings, a dry vagina, and decreased libido. So let’s think this through, shall we?
Here's my breakdown of who’s who:
Particularly if a BRCA mutation carrier has already had bilateral prophylactic mastectomies (i.e., no cancer present), there should be no hesitation regarding HRT use, barring other medical contraindications.
If a woman has had mastectomies for estrogen-driven cancer, that's a more difficult path to navigate, and for the most part, she should not take HRT (except vaginal estrogen is okay).
BRCA-1 mutation carriers have a 70% chance of making an estrogen negative cancer, so HRT has little impact on her future cancer risk, and she can easily consider it. The literature supports this. I will note here that the addition of progesterone does seem to elevate risk a tad, and since BRCA-1 carriers do have about a 5% increase in uterine cancer, if she also chooses hysterectomy, then the progesterone would be eliminated, and thus the breast cancer risk associated with it.2
Ultimately, it is the BRCA-2 mutation carrier with intact breasts who might struggle with the decision of HRT to treat early surgical menopause because her potential breast cancer is 80% likely to be estrogen-driven. Here's the thing: removing ovaries prior to age 50 decreases future breast cancer risk by 50 to 70% in BRCA-2 (and by 37% in BRCA-1). The PROSE study showed that HRT use does not negate this profound protective effect of ovary removal on subsequent breast cancer risk in BRCA1/2 mutation carriers, although follow-up was only 3.6 years so we can only say that with certainty for short-term HRT use.3 Nevertheless, think of it this way: even if HRT largely takes away the 50-70% reduction in breast cancer risk that you would otherwise enjoy from removing ovaries, then that simply puts you right back where you were in terms of risk the day before your oophorectomy. Except now you won't get ovarian cancer.
So in almost all situations for BRCA mutation carriers, I advocate for HRT.
5. Can I use it if I have a family history of breast cancer?
Family history in the absence of an inherited genetic mutation such as BRCA-2 should not preclude a woman from considering the use of HRT. Every perimenopausal and menopausal woman deserves a thorough and thoughtful discussion regarding the risks and benefits of HRT as it pertains to her personally, with attention focused on her individual constellation of symptoms, medical conditions, family history, etc.
6. I've had hormone positive breast cancer - is HRT out of the question for me?
Ohh, this is a great question. For everyone with a history of breast cancer, you can safely take vaginal estrogens to treat genitourinary (urinary and reproductive) symptoms. If you previously did not know that, you're welcome. Because that's a whole lot of misery that no woman needs.
Women with a history of estrogen-negative breast cancer can review the pros and cons of HRT for her as if she did not have breast cancer, but there could be other reasons to shy away from taking it.
Therefore, it is the woman with an estrogen-driven breast cancer who needs to be cautioned against liberal use of systemic HRT (patches, pills, etc).
Look, anti-estrogen pills have been shown in countless studies to decrease the recurrence of breast cancer between 50 and 65%, and to concurrently reduce the risk of new breast cancers in the same or opposite breast by 50%, so it does not make any intuitive sense to be taking estrogen when the treatment is an anti-estrogen. However, having made that obvious statement, it is my personal practice to allow every woman the opportunity to discuss her individual cancer risk profile with careful consideration of quality of life.
We oncologists now rely heavily on genomic testing of breast cancer tissue to determine the benefit of recommended therapies, specifically chemotherapy; however, more recently, these same genomic studies can help inform decisions regarding both radiation therapy and anti-estrogen therapy duration (2 years, 5 years, or 10 years).
Although not mainstream (yet), I use these genomic studies (such as MammaPrint and Oncotype Dx) in combination with a liquid biopsy - a blood test looking for circulating tumor DNA that belonged to your original cancer - to provide women with objective information that helps them contemplate the use of HRT despite a personal history of breast cancer. Answering this question with a flat-out, “No, no to HRT,” denies women the opportunity to engage in a gray area conversation; it's not black and not white.
7. Is progesterone safe? I heard it's the progesterone that caused the increased risk of cancer?
The short answer is, “progesterone is not safe.” But the increased risk is again small.
The nuance here is that there are many different types of progesterone, so let’s look at the data together so you can understand what the risks are.
The infamous Women's Health Initiative study published in July 2002 implicated progesterone in the form of medroxyprogesterone acetate (MPA) as the reason for the (not statistically significant) increase in breast cancer in those taking MPA alongside Premarin (estrogen made from horse urine). Especially since the Premarin-alone study arm demonstrated decreased breast cancer risk, the MPA seemed to be the likely cancer culprit.
Let's look at a few more recent and informative hormone studies that zero in on the progesterone connection.
A 2023 study analyzed the effects of PremPro (the old-school Premarin plus MPA) versus transdermal 1.5 mg estradiol and 200 mg oral micronized progesterone.4
15 healthy postmenopausal women in each group took the HRT for two 28-day cycles with breast biopsies before and after the HRT use.
The researchers analyzed over 28,000 genes for changes, and as it relates to breast cancer development, they identified 198 adverse changes for Prempro and 34 for the more modern formulation.
In other words, the combined therapy of PremPro increased breast cancer gene expression much more than the current combinations (transdermal estradiol + oral micronized progesterone). In other words, don’t use PremPro.
But was it the estrogen or the progesterone causing the changes?
A 2017 Swedish study looked at 290,196 women over 40 years old who used HRT during the 7-year study period, and they compared them with the Swedish female background population.5 The authors noted a 5% increase in breast cancer for estrogen-only and 40% for estrogen plus progesterone, again implicating progesterone as possibly causative, much more so than estrogen alone.
A 2022 study looked at HRT formulations and breast cancer risk by matching 43,183 women who already had breast cancer to 431,830 women who didn’t have breast cancer.6 From this comparison, they could analyze the different formulations of HRT in both groups and see if taking any type elevated breast cancer risk… only the synthetic progestin (MPA again) showed a statistically significant 28% increase in risk. Not bioidentical estrogen (structurally identical estrogen molecules such as estrodiol), not animal-derived estrogen, and not micronized (reduced-size) progesterone.
So is progesterone safe? Yes and no. Progesterone is safe-ish.
It is likely contributing more than estrogen when it comes to breast cancer risk. However, just as I noted that estrogen’s risks for breast cancer are real but not astronomical, the same applies to progesterone.
This 2020 study compared 98,611 women aged 50-79 who had breast cancer with 457,498 women who never used HRT.7 The findings were:
Estrogen alone:
15% increase in breast cancer risk.
Estrogen + Progesterone combination:
80% increase in breast cancer risk.
These percentages sound alarming, but let’s break them down:
For every 10,000 women using estrogen alone:
3 more cancers in younger women
8 more cancers in older women
For every 10,000 women using estrogen + progesterone:
9 more cancers in younger women
36 more cancers in older women
In other words, even in this highest-risk subgroup of older women on combined therapy, we’re talking about a 0.36% increase—a fraction of one percent. In the grand scheme, this is not a large number. And importantly, many of these women on HRT likely experienced significant health benefits.
There you have it—I hope you found these insights as illuminating as I did. One of the things I appreciate most about Dr. Funk is her commitment to backing everything she shares with high-quality scientific studies.
Neither of us is here to take sides; we believe this is a highly individualized decision, and we’re here to provide you with the research so you can make an informed decision about HRT in collaboration with your own healthcare provider.
Stay tuned for part two of this discussion, where we’ll dive into mammograms, and breast cancer prevention tips, and explore potential HRT alternatives.
P.S. When we talk about bio-identical hormones, we are not suggesting you go get a compounded version. You can get bio-identical hormones on prescription, covered by insurance, from a qualified MD trained in menopausal care.
There are so many ways to connect with Dr. Funk, depending on what you wish to address! Here are several suggestions:
Collaborative Group On Epidemiological Studies Of Ovarian Cancer; Beral V, Gaitskell K, Hermon C, Moser K, Reeves G, Peto R. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. Lancet. 2015 May 9;385(9980):1835-42. doi: 10.1016/S0140-6736(14)61687-1. Epub 2015 Feb 13. PMID: 25684585; PMCID: PMC4427760.
Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, Isaacs C, Olopade OI, Neuhausen SL, van 't Veer L, Eeles R, Evans DG, Tomlinson G, Matloff E, Narod SA, Eisen A, Domchek S, Armstrong K, Weber BL; PROSE Study Group. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005 Nov 1;23(31):7804-10. doi: 10.1200/JCO.2004.00.8151. Epub 2005 Oct 11. PMID: 16219936.
Lalitkumar PGL, Lundström E, Byström B, Ujvari D, Murkes D, Tani E, Söderqvist G. Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women. Int J Mol Sci. 2023 Feb 18;24(4):4123. doi: 10.3390/ijms24044123. PMID: 36835533; PMCID: PMC9959219.
Abenhaim HA, Suissa S, Azoulay L, Spence AR, Czuzoj-Shulman N, Tulandi T. Menopausal Hormone Therapy Formulation and Breast Cancer Risk. Obstet Gynecol. 2022 Jun 1;139(6):1103-1110. doi: 10.1097/AOG.0000000000004723. Epub 2022 May 3. PMID: 35675607.
Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. 2020 Oct 28;371:m3873. doi: 10.1136/bmj.m3873. PMID: 33115755; PMCID: PMC7592147.
Do you have any input on the value of using HRT at all?