Hormone Replacement Therapy Increases Ovarian Cancer Risk

What You Need to Know: Taking hormone replacement therapy (HRT) for menopause, even for just a few years, is associated with a small increased risk of developing the two most common types of ovarian cancer, according to a detailed re-analysis of all the available evidence.

The Evidence: The findings from a meta-analysis (a study of a collection of studies) of 52 epidemiological studies, involving a total of 21488 women with ovarian cancer, almost all from North America, Europe and Australia, indicate that women who use HRT for just a few years are about 40% more likely to develop ovarian cancer than women who have never taken HRT.

“For women who take HRT for 5 years from around age 50, there will be about one extra ovarian cancer for every 1000 users and one extra ovarian cancer death for every 1700 users”, explains study co-author Professor Sir Richard Peto from the University of Oxford in the UK.

The effect of HRT on the risk of developing ovarian cancer was the same for the two main types of HRT (preparations containing oestrogen only, or oestrogen together with a progestagen). Likewise, the proportional increase in risk was not materially affected by the age at which HRT began, body size, past use of oral contraceptives, hysterectomy, alcohol use, tobacco use, or family history of breast or ovarian cancer.

There are, however, four main types of ovarian cancer, and an increase in risk was seen only for the two most common types (serous and endometrioid ovarian cancers), and not for the two less common types (mucinous and clear cell ovarian cancers).

My Take: While hormone replacement therapy can provide benefits for selected individuals, this study reminds us to be prudent: If you must use HRT (for example, for hot flashes not controlled by acupuncture, exercise, and attention to triggers such as heat, caffeine, alcohol, stress, and spicy foods), use the lowest dose of HRT that you can, for as short a duration as possible. HRT can also increase the risks of breast cancer and cardiovascular events (but may lower your risk of colon cancer, and help with hot flashes (among other symptoms of menopause). I’m Dr. Michael Hunter.

References: 

  1. Collaborative Group on Epidemiological Studies of Ovarian Cancer. Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies. The Lancet, 2015 DOI: 10.1016/S0140-6736(14)61687-1
  2. The Lancet. “Short-term use of hormone replacement therapy associated with increased ovarian cancer risk.” ScienceDaily. ScienceDaily, 12 February 2015. <www.sciencedaily.com/releases/2015/02/150212211945.htm>.

Hormone Replacement Therapy, Genetic Changes, and Breast Cancer

hormone magnifying glass estrogen

What You Need to Know: Hormone replacement therapy – for women struggling with symptoms related to menopause – has been linked to an increased risk of breast cancer. But, does this mean that all forms of hormones confer an equal risk? The answer may be no.

Researchers have measured activity of genes associated with breast cancer in women before and while, they took different types of hormone replacement therapy (HRT). They found that an HRT used in the famous Women’s Health Initiative (WHI) trial had a greater activating effect on these genes than a “natural” formulation applied via an estrogen gel applied to the skin in combination with oral progesterone. This shows that varying the HRT and the way it is taken can have very significant effects on the genes associated with breast cancer.

What’s New? The type of HRT a woman takes, and the way it is taken, can have a significantly different effect on genes associated with breast cancer. This finding opens the way to identify which forms of HRT have minimal effect on breast cancer. It also gives the long-term possibility of personalising HRT according to the genes which a woman expresses.

Background: Since the publication of the Women’s Health Initiative report on HRT in 2002, many women have been worried about the effect of HRT on breast cancer. The International Menopause Society states that the increase in breast cancer is small, but that recommends that HRT be individually prescribed, depending on a woman’s family and medical history. However, at a deeper level the problem has been; how do we know what HRT actually does to the breast at a genetic level?

The Evidence: For the study, researchers from the Karolinska Institutet in Sweden, recruited a group of 30 healthy women, and took two samples of breast tissue from each, using a needle biopsy. Each tissue sample was then tested to measure the activity of 16 genes known to be associated with a greater risk of breast cancer. The women were then divided into two groups, and given HRT for 2 cycles of 28 days.

15 women took oral HRT, using CEE/MPA (this is a synthetic conjugated equine estrogen, plus medroxyprogesterone acetate, which was used in the WHI trial). The other 15 were given E2/P, which is estradiol gel plus oral micronised progesterone. Estradiol is a type of estrogen found in the body, so can be considered more “natural” than the CEE/MPA formulation. The estrogen (E2) was applied to the skin in a gel. The progesterone was micronised (i.e. put into very small particles) and taken orally.

At the end of the HRT cycles, the women then underwent the second breast biopsy. As lead researcher, Professor Gunnar Soderqvist said: “30 patients is quite a high number of patients for this type of analysis. The assessment of all genes both before and during treatment for the change in gene expression means that each woman was her own control, which adds to the strength of the study.”

Results: The researchers used PCR analysis to confirm that the CEE/MPA HRT changed the expression of 8 out of 16 genes (50%), whereas only 4 out of 16 genes (25%) were expressed differently in women taking the E2/P HRT. This difference was shown to be highly statistically significant.

What does this mean? Professor Gunnar Soderqvist continued: “Until now, it has not been possible to assess breast gene regulation in healthy women in vivo. This is the first study ever describing effects in healthy women during these HRT treatments and shows very important differences mostly in favour of “natural” treatment with the gel containing estradiol/ oral micronised progesterone when compared with “synthetic “oral CEE/MPA.

The study does not show that either HRT formulation “causes cancer,” but it does show that the type of HRT and perhaps the route of administration will cause differences in genes associated with breast cancer. We can conclude by saying that natural treatment with the estrogen gel and oral progesterone affects gene regulation and surrogate markers for breast cancer risk (such as mammographic density and breast cell proliferation) considerably less than the conventional synthetic treatment which stopped the WHI study.”

Incoming International Menopause Society President, Professor Rod Baber (Sydney) said: “This very important study show that use of HRT combining a transdermal estradiol preparation with oral micronised progesterone causes significantly less expression of genes associated with breast cell proliferation and breast cancer than the more traditional HRT combination of conjugated estrogens plus medroxyprogesterone.

The basic science from this study supports the evidence we have from clinical trials such as the French E3N trial, which shows that the choice so estrogen and progestogen and the mode of delivery is important in reducing any risk of breast cancer possibly associated with long term HRT.

My personal rule is this: Don’t use HRT to reduce your risk of heart attack, stroke, or dementia. If you need HRT to deal with symptoms such as severe hot flashes (and relatively non-toxic interventions such as acupuncture don’t work), choose the lowest dose of HRT that helps, and use it for as short a time as needed. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: International Menopause Society. “For the first time, proof of what hormone replacement therapy does to genes involved in breast cancer.” ScienceDaily. ScienceDaily, 2 May 2014. <www.sciencedaily.com/releases/2014/05/140502172035.htm>.

HRT and Breast Cancer: Risk Varies by Race, BMI, and Breast Density

Summary: The risk of getting breast cancer risk for those who have used hormone replacement therapy (HRT) varies by several factors.

Background: Studies have associated HRT with an increase in breast cancer risk. However, differential risks by body mass index (BMI) and breast density have been reported. In addition, studies on the effect of HRT use on breast cancer risk among black women have been inconsistent.

Current Study: Researchers from the University of Chicago (USA) analyzed 1,642,824 screening mammograms, including 9,300 breast cancer cases. All women were postmenopausal, and were part of the Breast Cancer Surveillance Consortium (a US screening mammogram registry). Data on HRT use were analyzed by race/ethnicity, age, BMI, and breast density.

Results: A greater than 20% increase in risk of breast cancer was associated with HRT among white and Hispanic women, but not black women. HRT was more strongly associated with with breast cancer risk in women with low or normal Body Mass Index, but not among those with a high BMI. In addition, women with denser breasts had an increased chance of getting breast cancer among those ho took HRT.

HRT was not linked with breast cancer for women with a high BMI and low breast density, but was associated with risk among those with low or normal BMI and high breast density.

My take: This study is the largest to date to investigate the association between HRT and breast cancer by covariables such as race/ethnicity, BMI, and breast density, Still a caveat is in order: The results were based on data for which we have no details regarding HRT type and duration of use.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minuteable now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Journal of the National Cancer Institute, 03 September 2013

Hot flashes: Risk Factors

Mature woman white smiling

Over the next several issues, I’ll turn to hot flashes: What are the risk factors, what is the pathophysiology, and management. Today, we begin with factors associated with hot flashes for patients with or without cancer.

Risk Factors: Both men and women can get hot flashes due to hormonal changes that occur during the natural aging process, although hot flashes are more common among midlife women. Age, race, ethnicity, educational level (equivocal), smoking, genetics, and body mass index can play roles. Some of  my patients see exacerbations with alcohol, exposure to heat, stress, spicy foods, and caffeine.

Race: Some studies point to African Americans having a greater risk for hot flashes (in addition to greater severity) as compared to other races. Here are the results from the Study of Women’s Health Across the Nation for combined hot flash and night sweat prevalence: Japanese 18%; Chinese-Americans 21%; whites 31%; Latinas 21%, and blacks 46%.

Smoking: The few studies that address the issue suggest a link between smoking and hot flashes. Smoking can alter estrogen metabolism in at least 4 ways.

Heart: Women who have hot flashes for 6 days or more over 2 weeks (especially those who are overweight or obese) have a higher cardiovascular risk. The role of weight and body mass index is less clear.

Genes: Research into the link between genetics (estrogen metabolism and receptor genes) and hot flashes appears promising. For example, women with a change (polymorphism) in a gene spot called CYP1B1 are at a 1/3 greater risk of reporting more severe and persistent hot flashes.

Cancer-related risk factors: These are predominantly related to the rapidity of hormone withdrawal. Among women, this is most commonly a drop in internal estrogen levels; with men, it is a drop in testosterone. For women, this may be linked to stopping hormone replacement therapy (HRT) when hormone-dependent breast cancer is diagnosed, the start of anti-estrogen therapies for treatment, chemotherapy-induced disruption of ovarian function, or damage to the ovaries (for example removal or radiation). Younger women are less likely than midlife women to have menopause induced by chemotherapy. In men, hot flashes are most commonly associated with anti-testosterone treatments for prostate cancer.

Certain cancers can be due to secretion of hormones by the cancer itself. Examples include some carcinoid tumors, medullary thyroid cancer, pancreas cancer, and kidney cancer.

I’m Dr. Michael Hunter. In my next blog, I’ll look at the physiology of hot flashes: Why do they occur?

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Coming Soon for iPad  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minutes. Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Thank you.

Breast Invasive Lobular Carcinoma: Link to HRT

Patients often wonder why they got a particular cancer. While we  cannot know with certainty why a particular individual got a cancer, we know of risk factors that increase the odds of getting it. Today, we look at the association of hormone replacement therapy (HRT) and a particular type of breast cancer, lobular carcinoma.

The observation: Post-menopausal hormone replacement therapy can significantly increase the risk of the less-common lobular form of breast cancer.

What’s lobular carcinoma? This breast cancer subtype involves the lobules, grape-like structures in the breast that contain milk-producing glands. Lobular carcinoma accounts for only about 15 percent of all invasive breast cancers, and is typically hormonally sensitive. However, lobular breast tumors also present a clinical challenge because they can be more difficult to detect both by clinical examination and by mammography (as compared to the more common ductal cancer).

English: Lobular Breast Cancer. Single file ce...
Lobular Breast Cancer. Single file cells and cell nests. (Photo credit: Wikipedia)

The data: In a study published in 2008 in Cancer Epidemiology, Biomarkers and Prevention, of more than 1,500 postmenopausal, western Washington women, my friend and colleague Christopher Li, MD found that current users of combined HRT had a 2.7-fold and 3.3-fold elevated risk of lobular and ductal-lobular cancer, respectively, regardless of tumor stage, size or number of lymph nodes involved. Only women who used combined HRT for three or more years faced an increased risk of lobular cancer. Among mixed ductal-lobular cases, hormone therapy increased the risk of tumors that were predominantly lobular but not tumors that had predominantly ductal characteristics.

Bottom Line: Postmenopausal women who take combined estrogen/progestin hormone-replacement therapy for three years or more face a fourfold increased risk of developing various forms of lobular breast cancer. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. And have a great day!