Megestrol and ER+ PR+

Hi.  I was diagnosed with stage IIIA endometrial cancer that metastisized to my ovaries. I had hysteretomy then chemo, radiation, more chemo.  Have been taking megestrol for appetite and then had lab work done on my slides which determined I was estrogen and progesterone receptor positive (90% both) w/Allred score of 8 in both.  My Dr. said to keep taking the megestrol, but I'm concerned this will cause additional cancer.  She left it up to me whether or not to cont. taking it and said the only risks were wt. gain and blood clots.  How do I know it won't cause cancer?  I understand that it affects the estrogen, but I don't understand the progesterone part since megestrol is a progestin. Am I getting too much progesterone?  Should I see an endocrinologist or be tested in some way?  I'm taking 80 mg 2x/day. I guess this is considered HRT? Megestrol is synthetic, isn't it? If I cont. taking it should I take a natural type?  I'm so confused over this.  

The lab test also showed immunohistochemical analysis of adenocarcinoma for erbB-2 protein is negative - what does this mean?  

[Annekathryn Goodman, M.D.]

hi there,
In general i agree with your doctor. Progesterones (megace being one of them) reduces growth rate of endometrial cancer. There is alot of lab data showing this. Unlike breast cancer, if endometrial cancer cells have a progesterone receptor, there is more of a chance the progesterone therapy will shut down the growth of the cancer. Having said that, the published literature on the topic is mixed. i have pasted a review below that summarizes some studies. the conclusion is that it is not clear that progesterone is helpful. I think one has to decide individually whether to use it or not.
It is important to discuss this with your doctor
best wishes



Martin-Hirsch P L, Jarvis G, Kitchener H, Lilford R. Progestagens for endometrial cancer. Cochrane Database of Systematic Reviews 1999, Issue 4. Art. No.: CD001040. DOI: 10.1002/14651858.CD001040.

Background
Endometrial cancer is the most common genital tract carcinoma in many western countries, with the majority (approximately 75%) of women presenting with stage 1 disease. The overall unadjusted five year survival for stage 1 disease is relatively high at 75% , but women with poor prognostic factors within stage 1 can have a survival expectancy as low as 26%. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. We have reviewed the effectiveness of this therapy.


Objectives
Progestagen therapy following primary surgery for endometrial cancer has been advocated to reduce the risk of recurrence. The objective of this review was to assess the effect of adjuvant progestagen therapy in endometrial cancer.


Search strategy
We searched the Cochrane Gynaecological Cancer Group trials register and MEDLINE up to May 1999.


Selection criteria
Randomised trials of progestagen therapy in women who have had surgery for endometrial cancer.


Data collection and analysis
Trial quality was assessed and two reviewers abstracted data independently.


Main results
Six trials involving 4351 women were identified. Three trials included women with stage one disease only, whereas three included women with more advanced disease. Based on five trials, overall survival was not improved by adjuvant progestagen therapy (OR 1.05, 95% CI 0.88 to 1.24). Endometrial cancer deaths and relapse of disease appears to be reduced by progestagen therapy OR 0.88 95% CI (0.71-1.1) and 0.81 95% CI (0.65-1.01) respectively. However, non-endometrial cancer related deaths were more common in women treated with progestagens OR 1.33 (1.02-1.73).


Authors' conclusions
Current evidence does not support the use of adjuvant progestagen therapy in the primary treatment of endometrial cancer.