HRT and Cancer

By Dr Ornella Cappellari

Nowadays with easy internet access and the plethora of information we find online, we can end up being literally overwhelmed with knowledge.

But what about topics like menopause, cancer and Hormonal Replacement Therapy (HRT)? Do we really know what is available or have the ability to understand what the choices are? And even if we keep ourselves informed, are we able to discern what the right options are? Just like other situations concerning the female body, it would be preferable to at least have an idea of what is going on and what is the best way to deal with such delicate issues.

Cancer and HRT is one of the most controversial topics surrounding the menopause. To start with, we need to make a distinction between different HRT treatments; there are 2 main types of HRT, estrogen only and combined (estrogen plus progestogen). Estrogen is a hormone produced by our ovaries. Progestogen is a steroid hormone that binds and activates the progesterone receptor which in other words acts similarly to progesterone. There is a third, less commonly known type of HRT called Tibolone.  Tibolone is a synthetic steroid that acts similarly to estrogen and progesterone. There are many different formulations including tablets, skin patches, cream and gels. There are very few specific studies on the effects of different formulations: most of the studies are based on HRT treatment via tablets and patches.

Which is the best choice here? Trying to prevent cancer recurrence or trying to keep up with the symptoms?

Endometrial Cancer

EC (Endometrial Cancer) is one of the most common types of cancer in western countries. Sometimes, it can even be the underlying cause of early menopause. One of the most effective treatments for this type of cancer is hysterectomy which can led to premature menopause (most of the time the uterus, fallopian tube and ovaries are removed: this prevents estrogen production). EC is usually a post-menopausal disease, but, in many cases it can develop in patients who are premenopausal. Therefore, menopausal symptoms, especially for women undergoing surgery are very common. On top of that, menopausal symptoms induced by surgery tend to be more severe than those occurring during a natural menopause.

Although no solid scientific data exists to demonstrate that HRT treatment is detrimental to EC cancer survivors many clinicians are still reluctant in prescribing it (European Journal of Cancer, 2014)1. This creates a lot of confusion between women for many different reasons: some of the patients are too young to undergo menopause (early menopausal state creates several hormonal unbalances, and risk factors can increase the onset of other pathologies such as severe osteoporosis, cardiovascular diseases, deep vein thrombosis and many others) and others just suffer from such severe menopausal symptoms that HRT seems a valid alternative or an appealing one. So, which is the best choice here? Trying to prevent cancer recurrence or trying to keep up with the symptoms? What are the numbers?

At present, the clinical community seems to agree that HRT is not a safe option after having had cancer but there is not enough strong data available on this subject. Endometrial cancer has been widely monitored in the Million Women study (Lancet 2005)2. From this study, it emerged that estrogen only HRT is not safe after EC but the combined therapy seems to be well tolerated. However, other available studies do not show an increase in recurrence or decrease in survival among women with endometrial, ovarian or cervical cancer who use HRT (The Obstetrician and Gynecolgyst 2014)3. The side effect of using combined HRT therapy after EC cancer is that it seems to increase recurrence in breast cancer or even cause a predisposition to it.

…even if the raw numbers seem to indicate a trend, this may be due to the innate differences between individual participants and not because the particular HRT is actually having an effect.

Breast Cancer

Breast cancer can be classified into receptor negative (tumor does not respond to hormonal therapy) and receptor positive (tumor does respond to hormonal therapy). Many studies have been done; the largest one being the HABITS4study. After this Randomized Controlled Trial (RCT), the medical community established that HRT treatment was not a safe option for breast cancer survivors. This study, however, was carried out over a decade ago in 2004 and many more have followed. What emerges from the subsequent studies is that there is a lack of consistency in the data and that the studies are not designed properly. Moreover, most of them did not have any statistical significance meaning that, even if the raw numbers seem to indicate a trend, this may be due to the innate differences between individual participants and not because the particular HRT is actually having an effect5. In other words, there is the likelihood that a relationship between two or more variables is caused by something other than random chance. Therefore, there are cases of a negative outcome in cancer survivors that used HRT treatments but there is not a strong indication that this is more likely compared to patients without a history of cancer.

Consolidating these scientific studies, we can only conclude that there is not enough evidence, at least given by properly designed studies, to suggest that HRT treatment massively increases the recurrence of cancer.

The HABITS study was interrupted for safety reasons as well as the Stockholm6 study which failed to replicate HABITS study findings. Results of the Stockholm study show that HRT therapy seems to increase cancer occurrence in healthy women, but it makes little or no difference in cancer survivors (the data could, however, be clearer). Another interesting review published in 2017 in Nature Reviews Endocrinology7, aimed to analyze all the available data to provide a precise overview of the state of the art. What emerges is that there are a lot of benefits to HRT in addition to some risks. Benefits include delaying the onset of osteoporosis which can be painful and limiting cardiovascular diseases and deep vein thrombosis. The study also takes into account the increased risk of cancer, stating that a personalized therapy should always be administered. The most recent report by the British Menopause Society, supported by various scientific papers, declared that the risk of breast cancer recurrence in women undergoing HRT has been underestimated. This study considered most of the variables that were not calculated in previous studies and concluded that combined HRT has a 2.7% increased incidence of breast cancer reoccurrence and the risk increased with duration usage. However, on the positive side, it seems that estrogen only HRT therapy shows no increased risk and the risk decreases to normal once treatment is stopped.

Consolidating these scientific studies, we can only conclude that there is not enough evidence, at least given by properly designed studies, to suggest that HRT treatment massively increases the recurrence of cancer. Since quality of life is an aspect that cannot be discounted, the wisest probable choice for cancer survivor patients is to consider the lowest possible dose of HRT for the shortest period of time, only after exhausting alternative treatment options while under strict medical control. Moreover, patients should be aware of the existing risk in using HRT but also the benefits in a way that empowers them to make an informed choice as to what is best for them. At the end of the day, a personalized therapy8has to be approached as soon as possible because there are so many interfering factors (age, genetics, lifestyle) making it exceptionally difficult to draw the line of safety. What is certain though after all these studies is that doctors need to keep monitoring and women need to keep fighting for more available information in order to help them live a comfortable lifestyle.

References:

 

1. Eur J Cancer. 2014 Jun;50(9):1628-37. doi: 10.1016/j.ejca.2014.03.006. Epub 2014 Mar 28. Effects of hormone replacement therapy on the rate of recurrence in endometrial cancer survivors: a meta-analysis. Shim SH1, Lee SJ1, Kim SN2.

2. Lancet. 2005 Apr 30-May 6;365(9470):1517-8.Hormones and endometrial cancer–new data from the Million Women Study. Brinton LA,  Lacey JV Jr, Trimble EL.

3. DOI: 10.1111/tog.12146 The Obstetrician & Gynaecologist Hormone therapy in survivors of gynaecological and breast cancer. Amy Bregar, Kristin Taylor, Ashley Stuckey.

4. Endocrine. 2004 Aug;24(3):255-7.Hormone replacement in women with breast cancer: the HABITS study. Brincat M1, Muscat Baron Y, Ciantar E.

5. J Adv Pract Oncol 2015;6:322–330 Hormone Replacement Therapy: An Increased Risk of Recurrence and Mortality for Breast Cancer Patients? MOLLY LUPO, RN, MSN, ANP, NP-C, AOCNP JOYCE E. DAINS, DrPH, JD, RN, FNP-BC, DPNAP, FAANP, and LYDIA T. MADSEN, PhD, RN, AOCNS

6. European Journal of Cancer (2013) 49, 52– 59 Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial Mia Fahle´, Tommy Fornander, Hemming Johansson, Ulla Johansson, Lars-Erik Rutqvist, Nils Wilking, Eva von Schoultz.

7. Nat Rev Endocrinol. 2017 Apr;13(4):220-231. doi: 10.1038/nrendo.2016.164. Epub 2016 Oct. Hormone-replacement therapy: current thinking. Lobo RA.

8. Maturitas 73 (2012) 265– 268 The management of menopausal symptoms in breast cancer survivors: A case-based approach Ellen A.G. Lammerinka, Geertruida H. de Bockb, Carolien P. Schröderc, Marian J.E. Mouritsa.

Other sources:


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