Does HRT cause breast cancer? What the numbers actually show

For many women, this is the question behind every other question about hormone therapy. You may have heard that HRT causes breast cancer, or that the risk was overblown. Neither headline tells the whole story. The answer depends on what kind of hormones you take, how long you take them, and your own history. Here is what the major studies measured, in plain language.

The short answer

Some types of hormone therapy are linked to a higher chance of being diagnosed with breast cancer, and the size of that risk depends on the type of hormone, how long you use it, and your individual characteristics ^[1]. The Menopause Society calls the added risk rare: less than one additional case per 1,000 women per year of use, or about three additional cases per 1,000 women who use estrogen plus progestin for 5 years ^[1].

For context, breast cancer affects about one in eight US women ^[1]. The Menopause Society suggests putting the hormone-related risk in perspective. It is similar to the risk tied to modifiable factors like two alcoholic drinks a day, obesity, or low physical activity ^[1].

The details matter more than the headline. Below, we walk through the two big Women's Health Initiative (WHI) trials, the largest pooled analysis of observational studies, and what each one can and cannot tell you.

Combined therapy and estrogen alone are not the same

The WHI ran two separate randomized trials. Women who still had a uterus took estrogen plus a progestin, or a placebo. Women who had had a hysterectomy took estrogen alone, or a placebo ^[3]. Both trials used conjugated equine estrogens, and the combination added medroxyprogesterone acetate ^[3].

Estrogen plus progestin

The combination trial enrolled 16,608 women aged 50 to 79. It was stopped in 2002, after an average of 5.2 years, when breast cancer cases crossed a preset safety boundary ^[2]. Researchers estimated 8 extra invasive breast cancers per 10,000 women per year on the combination ^[2].

After a median of more than 20 years of follow-up, breast cancer was still more common in the group that had taken the combination: 584 cases versus 447 on placebo, an annual rate of 0.45% versus 0.36% ^[3]. Deaths from breast cancer were not significantly different between the two groups ^[3].

Estrogen alone

The estrogen-alone trial enrolled 10,739 women who had had a hysterectomy ^[3]. Here, the result went the other way. Over the same long follow-up, women who had taken estrogen alone had fewer breast cancer diagnoses than women on placebo, 238 versus 296, and fewer deaths from breast cancer, 30 versus 46 ^[3].

Why this matters for you: if you still have a uterus, The Menopause Society recommends an adequate progestogen alongside systemic estrogen to protect the uterine lining ^[1]. So for most women with a uterus, the combination results are the more relevant ones.

Age and past hormone use change the numbers

The average WHI participant was about 63 ^[3]. Updated FDA labeling for an approved estradiol and progesterone capsule breaks the WHI combination results down further ^[5]:

• All ages, 50 to 79: 9 extra invasive breast cancers per 10,000 women per year, 43 versus 35 ^[5].
• Ages 50 to 59: 6 extra per 10,000 women per year, 33 versus 27, a difference that was not statistically significant ^[5].
• Ages 50 to 59, no past hormone use: 2 extra per 10,000 women per year, 33 versus 31 ^[5].
• All ages, with past hormone use: 21 extra per 10,000 women per year, 46 versus 25 ^[5].

These numbers come from one oral combination, and the label says it is not known how well they apply to other doses, routes, or products ^[5]. Still, the pattern is worth noticing. Women who had used hormones before the trial, and so had more total years of exposure, saw the biggest increase.

How long you take it matters

The WHI tested hormones for a median of about 5 to 7 years, so it cannot say much about longer use ^[1]. For that, researchers turned to observational data. In 2019, the Collaborative Group on Hormonal Factors in Breast Cancer pooled studies that included 108,647 postmenopausal women who developed breast cancer ^[4].

Their main findings, in plain terms ^[4]:

• Every type of systemic hormone therapy studied was linked to some extra breast cancer risk, and that risk climbed steadily with years of use ^[4].
• The extra risk was larger for estrogen plus a progestogen than for estrogen alone ^[4].
• Among current users, risk was already higher in years 1 to 4, and about twice as high again in years 5 to 14 ^[4].
• After stopping, some extra risk lasted more than 10 years, but there was little extra risk after less than a year of use ^[4].
• Vaginal estrogens were the exception. They were not linked to extra risk ^[4].

The authors also put this in absolute terms. If the links are largely causal, 5 years of hormone therapy starting at age 50 would lead to about one extra breast cancer between ages 50 and 69 for every 50 women using estrogen plus a daily progestogen, one in every 70 using estrogen plus a progestogen taken part of the month, and one in every 200 using estrogen alone ^[4]. Ten years of use would roughly double those figures ^[4].

Observational studies show links, not proof of cause, which is why the authors framed their estimates as applying only if the associations are causal ^[4]. The Menopause Society cites the same pooled data, which showed risk increasing with duration for both estrogen alone and combined therapy ^[1].

Does the type of estrogen or progestogen matter?

This is where the evidence gets thinner. The Menopause Society says oral and transdermal estrogen appear to have similar effects on the number of breast cancers diagnosed, while vaginal estrogen has no effect ^[1]. Some, but not all, observational data suggest micronized progesterone may have a smaller association with breast cancer than synthetic progestogens such as medroxyprogesterone acetate, but randomized trials are needed to confirm that ^[1].

The schedule may matter too. In the 2019 pooled analysis, the extra risk during years 5 to 14 of use was greater when the progestogen was taken daily than when it was taken less often ^[4].

So a patch is not a breast cancer workaround. The route of estrogen matters for blood clots, where transdermal estrogen has not been linked to higher risk in observational studies ^[1]. For breast cancer, the evidence suggests route matters much less ^[1]. Read more in HRT and blood clots.

Mammograms while you are on hormones

Some hormone regimens can make breast tissue denser on a mammogram, which may make images harder to read ^[1]. In the WHI, women on the combination had more mammograms and breast biopsies than women on placebo ^[1], and FDA labeling notes an increase in abnormal mammograms needing further evaluation ^[5]. The breast cancers found in the combination group were larger, more likely to have spread to the lymph nodes, and found at a more advanced stage ^[5].

The Menopause Society advises regular breast cancer screening for all postmenopausal women, including those using hormone therapy ^[1]. The patient information for one approved product advises a breast exam and mammogram every year unless your provider tells you otherwise ^[5].

If breast cancer runs in your family

A family history raises your starting risk, but it does not appear to multiply the effect of hormones. The Menopause Society says most data do not show an added effect of hormone therapy on top of underlying risk factors such as age, family history, genetic risk, or benign breast disease ^[1]. Observational evidence suggests hormone therapy does not further increase the relative risk of breast cancer in women with a family history, or in women with BRCA 1 or 2 variants who have had their ovaries and tubes removed ^[1].

There is a catch. Because the relative increase is similar, the actual number of extra cases will be greater in women whose starting risk is higher ^[1]. That is why The Menopause Society says personal and family risk of breast cancer should be considered before starting ^[1], and why your clinician asks about it.

If you have had breast cancer

This is a different situation. FDA labeling for systemic estrogen plus progestogen lists breast cancer, or a history of it, as a contraindication ^[5]. The Menopause Society says systemic hormone therapy is generally not advised for breast cancer survivors ^[1]. ACOG advises women with a history of hormone-sensitive breast cancer to try nonhormonal therapies first ^[6].

The research in survivors is mixed. One randomized trial found more breast cancer recurrences in hormone users, while another found no difference in recurrence but more cancers in the other breast ^[1]. The Menopause Society says that if symptoms are severe and do not respond to other options, some survivors may choose hormone therapy together with their oncologist after a full discussion of the risks ^[1]. For vaginal dryness, low-dose vaginal estrogen may be considered in consultation with an oncologist, with more concern for women taking aromatase inhibitors ^[1].

If you have had breast cancer, talk with your oncologist before starting any hormone, including a vaginal cream.

Questions to bring to your clinician

• Do I need a progestogen, or does my hysterectomy mean I can take estrogen alone?
• How long do we plan to use hormones, and when will we review that plan?
• Given my family history, what is my starting risk?
• If my main symptom is vaginal dryness, is a vaginal treatment enough?
• When is my next mammogram due?

Breast cancer risk is one part of a bigger picture. Hormone therapy remains the most effective treatment for hot flashes and night sweats ^[1]. For women under 60 or within 10 years of menopause who have no contraindications, The Menopause Society finds the benefit-risk ratio favorable for treating bothersome symptoms ^[1]. For the rest of that picture, read is HRT safe?

Talking it through with WarriorBabe Health

A WarriorBabe Health clinician reviews your health history, including any breast cancer in you or your family, before deciding whether hormone therapy fits. Options include oral estradiol, an estradiol patch, estradiol cream, and a progesterone capsule for women with a uterus. You can compare them on our hormone treatments page.

Our hormone products are compounded by a licensed pharmacy. Compounded drugs are not FDA-approved, which means the FDA does not review their safety, effectiveness, or quality before they are marketed ^[7]. The studies in this article looked at FDA-approved products, so ask your clinician how they apply to you.

Wondering whether hormone therapy could be an option? Take the 2-minute quiz. A licensed clinician makes the final call on whether any prescription is appropriate.

This article is for general information. It is not medical advice and does not replace a visit with a licensed clinician who knows your history. Do not start, stop or change a medication without talking to your clinician. If you think you are having a medical emergency, call 911.