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Mirena for Lynch patients?

In gynaecology we moved from major surgery through laparotomy, to laparoscopic surgery to single incision surgery and finally to non-surgical treatment of endometrial pathology within the last 10 years. Conditions that required patients staying in hospital for several weeks some years ago can now be treated reasonably successfully without surgery.

Not too long ago we discussed the results of a randomised trial using Mirena for menorrhagia. The success rate was approximately 70%. Nevertheless, about 30% of patients still required a hysterectomy at 2 years from commencement of treatment.

There is now even a mini-Mirena in the pipeline, which our colleagues in the US and Europe already use. In Australia TGA assesses and approval is pending. It will be a smaller version of the “normal” Mirena and probably called Skyla in Australia (like in the US). Mirena releases the hormone at an initial rate of 20 micrograms per day, which declines to a rate of 14 micrograms after 5 years. Skyla releases 14 micrograms per day, which declines to 5 micrograms per day after 3 years.

The levonorgestrel intrauterine device (Mirena) is approved for contraception and treatment of menorrhagia but reports on cancer treatment pop up regularly.

When I prepared for a presentation about Lynch syndrome, I realised that there is not much we can offer to women for the prevention of endometrial cancer. Despite strong recommendations for endometrial sampling and transvaginal ultrasound (those recommendations lack any evidence), risk-reducing, prophylactic surgery seems to be the only avenue we can offer to protect these women at present. However, someone pointed out to me that Mirena is already used in patients who are on Tamoxifen for breast cancer. As we are all aware these women are at high risk of developing endometrial cancer. Given that we use Mirena to treat endometrial cancer, could possibly Mirena be used to protect against endometrial cancer? 

Keep in mind; Tamoxifen reduces the recurrence rate of breast cancer by 50% and increases survival from breast cancer by one third. Unfortunately, it increases the risk of endometrial polyps, endometrial hyperplasia and endometrial cancer significantly. Unfortunately, screening for endometrial cancer even in high-risk women, such as women on Tamoxifen is ineffective.

There is a recent paper on a randomised trial that I wanted to briefly present here. The paper comes from Hong Kong and was published only a few weeks ago by Alice Wong and colleagues in Obstetric and GynecologyThe aim of the authors was to determine if Mirena would decrease the development of endometrial pathology in patients who are on Tamoxifen for breast cancer.

They randomised 129 Chinese women to either receive Mirena or nothing and followed them for up to 5 years. The majority of the women (94) completed 5 years follow up. Women were comparable at baseline. There was a significant reduction in the number of de novo endometrial polyps. While 16 of 65 (32%) women in the control group developed endometrial polyps, only 2 of 64 (4%) patients in the Mirena group developed those polyps. There was no difference in the incidence of endometrial hyperplasia with or without atypia or endometrial cancer because the study was too small.

Importantly, there was no difference in the recurrence rate or breast cancer prognosis between patients who had a Mirena and those who did not.

As a gynaecological oncologist, I would be interested if Mirena would be effective to reduce the risk of endometrial cancer in women who are at very high risk (such as Lynch carriers)? Patients with breast cancer have a 150% increased risk of endometrial cancer compared to the general population.

Wouldn't it be great to know if we should recommend the Mirena to breast cancer patients who are on Tamoxifen to minimise their endometrial cancer risk. Wouldn't it be great to know if we should recommend Mirena to obese and very obese women who are on medication for hypertension and/or diabetes and quite likely will develop endometrial cancer in the future. I would also love to know if Mirena is effective to protect Lynch carriers from develoiping endometrial cancer. 

Our randomised feMME trial examining Mirena ± Mirena and weight loss ± Mirena and Metformin hast started, has been modified and version 2 will kick off very soon. I will keep you updated. We will enrol patients (public and privately insured) in Queensland first to make sure that all our processes are in place and working. After a couple of months we will then be able to also enrol patients from all other states and internationally if gynaecologists are interested.

Imagine if women diagnosed with endometrial cancer would not have to have a major operation and could be treated in your clinic. 

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Comments

  • Andreas Obermair 10/06/2013 6:53pm (6 years ago)

    There is no such information available for Lynch patients. We looked at endometrial cancer and endometrial hyperplasia with atypia (which is a precancerous condition). In treating patients (this is not prevention) we had a 70% complete pathological response rate. We also know that recurrences are common after removal of Mirena.
    In the setting of endometrial cancer prevention I suspect that we will need very large numbers of patients and we probably won't be able to do that study with Lynch patients alone.
    Our group is currently looking into such a study but we are limited by funds. The study I am thinking of could possibly completed within 12 months.

  • margaret 09/06/2013 10:40pm (6 years ago)

    What information is available about the long term prognosis of endometrial hyperplasia with atypia with
    Mirena IUS rather than hysterectomy?

  • Dirk R G Janssens 09/06/2013 12:30am (6 years ago)

    Dear Collegue,
    Congratulations for embarking this issue. Yes it would be great to know the quantitative impact on prevention by inserting whatever type of IUS delivering a daily dose of 20 mcg of LNG during 5 to 10 y in high and moderate risk patients for endometrial cancer. Only a well conducted interventional study will be able to tell this. Waiting for Godot ? I already posted a comment on LinkedIn discussion in the 'Controversies ... ' group, referring to our own (very modest) contribution in this field. Please contact Dirk Wildemeersch ( d.wildemeersch@skynet.be ) if you want to know more about the publication, which is in preparation. Thanks for keeping me / us informed about your results. Confraternally.

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