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 Gynecology. The 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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