Thank you for your excellent comment. I applaud your proactive work with respect to potential use of hormonal (anti-estrogen) therapies against ovarian cancer. Anti-estrogen treatment for breast cancer is well established and is considered standard of care in that cancer area. Unfortunately, there are no large clinical studies that address the use of anti-estrogen therapies against ovarian cancer, although smaller studies do exist.

Several studies have indicated that estrogen plays a role in ovarian cancer. The first step is to convince your doctor to test your original tumor biopsy (assuming it was properly preserved) for estrogen & progesterone positivity. If your tumor is estrogen positive, it is a great idea to speak with your doctor regarding the potential use of anti-estrogen therapies. Please keep in mind that convincing your doctor to listen to this approach may be difficult because, to my knowledge, the FDA has not approved any anti-estrogen therapy for use against ovarian cancer. A great hormonal (anti-estrogen) therapy summary, presented in the context of breast cancer, can be found at http://www.breastcancer.org.

There are three major classes of anti-estrogen therapies/drugs.

The first class of drugs are referred to as Selective Estrogen Receptor Modulators or SERMs. Drugs in this class include tamoxifen, Evista (raloxifene), and Fareston (toremifene).

The second class of drugs are referred to as aromatase inhibitors or AI’s. Drugs in this class include Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole).

The third class of drugs are referred to as Estrogen Receptor Downregulators or ERD’s. Drugs in this class include Faslodex (fulvestrant).

You have inquired about updates regarding an AI know as Femara (letrozole). Aromatase is the enzyme required for the synthesis of estrogen via conversion of androgen to estrogen, which is the major source of estrogen in postmenopausal women. Aromatase is present in normal ovaries and other tissues (e.g., fat and muscle), including an estimated 33% to 81% of ovarian cancer tumor tissue. Aromatase inhibitors (AIs) block estrogen synthesis by inhibiting aromatase activity. In patients with recurrent ovarian cancer, single-agent AI therapy has been shown to elicit clinical response rates of up to 35% and stable disease rates of 20% to 42%. Given the limited treatment options for recurrent ovarian cancer and the favorable safety profile and convenient use, AIs are a rational option for prolonging platinum (drug)-free interval in recurrent ovarian cancer.

I should note, however, that further clinical studies are required to: (i) determine the efficacy of combination treatment with AIs and biological agents; (ii) determine the benefit of AIs for treating special subtypes of ovarian cancer (e.g., endometrioid type); and (iii) identify biomarkers for targeted patient selection. I have provided below a list of relevant studies relating to anti-estrogen therapy in the context of ovarian cancer. If you are only interested in those relating to Femara (letrozole), just scan the study titles for the word “letrozole” to identify those that interest you. A hyperlink to the medical abstract for each study is provided. Please feel free to print out all of these medical abstracts for your doctor, and then ask him/her to discuss this potential approach with you.

My search of http://www.clinicaltrials.gov for anti-estrogen therapy in the context of ovarian cancer produced the following: (i) 5 trials (1 recruiting) for tamoxifen, (ii) 0 clinical trials for raloxifene, (iii) 1 trial (0 recruiting) for toremifene, (iv) 1 trial (0 recruiting) for anastrozole, (v) 1 trial (recruiting) for exemestane, (vi) 3 trials (1 recruiting) for letrozole, and (vii) 1 trial (0 recruiting) for fulvestrant. In theory, you could search for trials involving “solid tumors” and each of these drugs, and you may find additional trials.

I trust this information is helpful. If you require additional information, please feel free to contact me. Best, Paul

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1: Arias-Pulido H, Smith HO, Joste NE, Bocklage T, Qualls CR, Chavez A, Prossnitz
ER, Verschraegen CF. Estrogen and progesterone receptor status and outcome in
epithelial ovarian cancers and low malignant potential tumors. Gynecol Oncol.
2009 Sep;114(3):480-5. Epub 2009 Jun 27. PubMed PMID: 19560192; PubMed Central
PMCID: PMC2756056.

2: Burges A, Brüning A, Dannenmann C, Blankenstein T, Jeschke U, Shabani N,
Friese K, Mylonas I. Prognostic significance of estrogen receptor alpha and beta
expression in human serous carcinomas of the ovary. Arch Gynecol Obstet. 2009 Jul
29. [Epub ahead of print] PubMed PMID: 19639330.

3: Korach J, Perri T, Beiner M, Davidzon T, Fridman E, Ben-Baruch G. Promising
effect of aromatase inhibitors on recurrent granulosa cell tumors. Int J Gynecol
Cancer. 2009 Jul;19(5):830-3. PubMed PMID: 19574768.

4: Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A. History of aromatase:
saga of an important biological mediator and therapeutic target. Endocr Rev. 2009
Jun;30(4):343-75. Epub 2009 Apr 23. Review. PubMed PMID: 19389994.

5: Argenta PA, Thomas SG, Judson PL, Downs LS Jr, Geller MA, Carson LF, Jonson
AL, Ghebre R. A phase II study of fulvestrant in the treatment of
multiply-recurrent epithelial ovarian cancer. Gynecol Oncol. 2009
May;113(2):205-9. Epub 2009 Feb 23. PubMed PMID: 19239974.

6: Tangjitgamol S, Manusirivithaya S, Khunnarong J, Jesadapatarakul S, Tanwanich
S. Expressions of estrogen and progesterone receptors in epithelial ovarian
cancer: a clinicopathologic study. Int J Gynecol Cancer. 2009 May;19(4):620-7.
PubMed PMID: 19509560.

7: Yang XY, Xi MR, Yang KX, Yu H. Prognostic value of estrogen receptor and
progesterone receptor status in young Chinese ovarian carcinoma patients. Gynecol
Oncol. 2009 Apr;113(1):99-104. Epub 2009 Jan 29. PubMed PMID: 19178934.

8: Issa RM, Lebeau A, Grob T, Holst F, Moch H, Terracciano L, Choschzick M,
Sauter G, Simon R. Estrogen receptor gene amplification occurs rarely in ovarian
cancer. Mod Pathol. 2009 Feb;22(2):191-6. Epub 2008 Aug 8. PubMed PMID: 18690166.

9: Langdon SP, Smyth JF. Hormone therapy for epithelial ovarian cancer. Curr Opin
Oncol. 2008 Sep;20(5):548-53. Review. PubMed PMID: 19106659.

10: Ramirez PT, Schmeler KM, Milam MR, Slomovitz BM, Smith JA, Kavanagh JJ,
Deavers M, Levenback C, Coleman RL, Gershenson DM. Efficacy of letrozole in the
treatment of recurrent platinum- and taxane-resistant high-grade cancer of the
ovary or peritoneum. Gynecol Oncol. 2008 Jul;110(1):56-9. Epub 2008 May 5. PubMed
PMID: 18457865.

11: Li YF, Hu W, Fu SQ, Li JD, Liu JH, Kavanagh JJ. Aromatase inhibitors in
ovarian cancer: is there a role? Int J Gynecol Cancer. 2008 Jul-Aug;18(4):600-14.
Epub 2007 Sep 25. Review. PubMed PMID: 17894799.

12: García-Velasco A, Mendiola C, Sánchez-Muñoz A, Ballestín C, Colomer R,
Cortés-Funes H. Prognostic value of hormonal receptors, p53, ki67 and HER2/neu
expression in epithelial ovarian carcinoma. Clin Transl Oncol. 2008
Jun;10(6):367-71. PubMed PMID: 18558584.

13: Walker G, MacLeod K, Williams AR, Cameron DA, Smyth JF, Langdon SP.
Estrogen-regulated gene expression predicts response to endocrine therapy in
patients with ovarian cancer. Gynecol Oncol. 2007 Sep;106(3):461-8. Epub 2007 Jul
10. PubMed PMID: 17624412.

14: Smyth JF, Gourley C, Walker G, MacKean MJ, Stevenson A, Williams AR, Nafussi
AA, Rye T, Rye R, Stewart M, McCurdy J, Mano M, Reed N, McMahon T, Vasey P, Gabra
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I am a recent AOC survivor interested in updates on the use of the Anti-Estrogen Drug -Femara.

Currently I am in remission after having recently completing surgery and chemo in
Aug 2009. I am 54 and concerned about the high rate of reoccurrence of my disease so I want to be proactive about future treatment options, especially Femara.

A recent lab test from my endocrinologist showed that my estrogen and progestrone levels, while still normal, were on the high side of normal and unusually high for someone my age, who had recently undergone a total hysterectomy/debulking surgery for advanced ovarian cancer.

I plan to ask my doctor to biopsy my tumor for estrogen receptor positivity.

Thanks in advance,
Kathie C
Lewis Center, OH
klc7172000@yahoo.com

Thank you for the comment. I agree with you that estrogen positivity testing and use of anti-hormonal therapy (e.g., Femara(r)) could benefit select ovarian cancer patients. Unfortunately, not as many women test ER+ with respect to ovarian cancer tumors as compared to breast cancer tumors. Due to the lower number of ER+ ovarian cancer tumors, estrogen positivity testing is often overlooked. The approach that you suggest is certainly the approach with respect to breast cancer in the U.S., but, unfortunately, not ovarian cancer. Hopefully this will change in the near future. In addition, the U.S. clinical study format generally begins testing with recurrent cancer patients, and then if successful, the tested drug is further tested in patients with earlier cancer stages. Herceptin(r) is a good example. It was initially tested and FDA-approved for Stage IV HER-2 positive breast cancer, but with time, it was eventually tested by M.D. Anderson for neoadjuvant use.

The benefit of anti-hormonal therapy is low toxicity. As you know, low toxicity becomes an important issue for ovarian cancer patients, especially those who experience multiply recurrences over time. It is great to hear that you experienced success (i.e., regression for 3 years) with respect to a malignant ovarian granulosa cell tumor.

As always, we invite any further thoughts or observations that may have in the future regarding ovarian cancer topics, and wish you continued success with the Organisation Gestosis Affiliated and Sponsored Hospitals (OGASH) and Ain Shams University in Cairo.

Best,

Paul