The Gynecologic Oncology department of the University of Texas, M.D. Anderson Cancer Center took a page out of the breast cancer treatment “playbook,” and conducted a single institution Phase II clinical trial using letrozole (Femara®) to treat recurrent, platinum and taxane resistant, high-grade cancer of the ovary and peritoneum. …The trial investigators concluded that 26% (8/31 pts.) of patients with ER+ … ovarian and primary peritoneal cancer derived a clinical benefit (stable disease (SD) + partial response (PR)) after treatment with letrozole (Femara®).
Pursuant to the breast cancer standard of care, breast tissue tumor is routinely analyzed to determine if it is “estrogen receptor positive” (ER positive or ER+), meaning that tumor growth is fueled by the hormone estrogen. It is well-known in the breast cancer area that hormonal therapy is a very effective treatment against breast cancer that is ER+. Sometimes referred to as “anti-estrogen therapy,” hormonal therapy blocks the ability of the hormone estrogen to turn on and stimulate the growth of breast cancer cells.
For decades, the anti-estrogen therapy of choice for treatment of ER+ breast cancer was tamoxifen. In 2005, several world-wide clinical trials reported that aromatase inhibitors (specifically, anastrozole (Arimidex®), exemestane (Aromasin®), and letrozole (Femara®) were more effective than tamoxifen in post-menopausal women with ER+ breast cancer. Aromatase inhibitor drug use is currently the standard of care for treatment of post-menopausal women with ER+ breast cancer, while tamoxifen remains the hormonal treatment of choice for pre-menopausal women.
The Gynecologic Oncology department of the University of Texas, M.D. Anderson Cancer Center took a page out of the breast cancer treatment “playbook,” and conducted a single institution Phase II clinical trial using letrozole (Femara®) to treat recurrent, platinum and taxane resistant, high-grade cancer of the ovary and peritoneum.
Thirty-three patients enrolled in the Phase II clinical trial, and each had measurable disease that tested ER+ pursuant to trial eligibility criteria. Twenty-three patients (74%) had received three or more prior chemotherapy regimens. Letrozole (Femara®) was administered at a dose of 2.5 mg orally once daily until disease progression or toxicity occurred. The median patient age was 63 years (ranging from 38 to 83 years).
The 31 patients evaluable for response received a total of 81 cycles (4 weeks per cycle) of therapy (ranging from 1 to 14 cycles per patient). The median treatment duration was 8 weeks (ranging from 4 to 52 weeks). The trial investigators reported that (i) none of the patients had a complete response (CR), (ii) 1 (3%) had a partial response (PR), and (iii) 7 (23%) had stable disease (SD). The median duration of clinical benefit (SD and PR) was 9 weeks (ranging from 7 to 46 weeks). The median follow-up for all patients was 25 weeks. All evaluable patients were monitored for toxicity. The most common adverse effects were fatigue (36%) and diaphoresis (21%). No grade 3 or 4 toxicities were reported, and no patients discontinued treatment owing to adverse effects. Eighteen patients (58%) went on to receive additional therapy with other agents.
Based upon the results above, the trial investigators concluded that 26% (8/31 pts.) of patients with ER+, platinum- and taxane-resistant, high-grade ovarian and primary peritoneal cancer derived a clinical benefit (stable disease (SD) + partial response (PR)) after treatment with letrozole (Femara®).
- Efficacy of letrozole in the treatment of recurrent platinum- and taxane-resistant high-grade cancer of the ovary or peritoneum, Ramirez PT, Schmeler KM, Milam MR et. al; Gynecol Oncol. 2008 Jul;110(1):56-9.
- Hormonal Therapy, Breastcancer.org, July 24, 2008 (webpage last modified).
Comment: Based upon the references listed above and below, it appears that the opening of clinical trials that utilize anti-estrogen therapy to treat ER+ ovarian cancer is long overdue. The “take away” from the M.D. Anderson clinical trial study results is that an ovarian cancer survivor should request her doctor to test the ovarian cancer tumor tissue obtained from surgery or biopsy for estrogen receptor positivity, so as to determine if she is eligible to use anti-estrogen therapy (within the context of a clinical trial) as part of an overall cancer treatment plan.
It is important to note that letrozole is a low side effect, oral drug. Moreover, M.D. Anderson’s letrozole monotherapy produced a 26% clinical benefit rate among ER+, platinum- and taxane-resistant, ovarian and peritoneal cancer patients, despite the fact that approximately three-quarters of the clinical trial patients were heavily pretreated with multiple lines of chemotherapy prior to their trial enrollment. It is promising to consider the potential clinical benefit that could be generated by anti-estrogen therapy in a neoadjuvant or adjuvant ovarian cancer treatment setting.
Additional Anti-Estrogen Therapy/Ovarian Cancer References:
- Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma, García-Velasco A et. al; Clin Transl Oncol. 2008 Jun;10(6):367-71(… “Ki67 nuclear expression >30% is predictive of complete response in advanced ovarian cancer. HER2/neu overexpression is scarce in our study. Positive ER [ER+] is an independent prognostic factor for OS [overall survival]. Further research with larger studies and hormonal treatment is guaranteed.)
- Estrogen-regulated gene expression predicts response to endocrine therapy in patients with ovarian cancer, Walker G et. al.; Gynecol Oncol. 2007 Sep;106(3):461-8. Epub 2007 Jul 10. (“OBJECTIVE: To explore the predictive value of estrogen-regulated gene changes as indicators of sensitivity in ovarian cancer patients treated with the aromatase inhibitor Letrozole. … CONCLUSION: These results suggest that expression levels of certain proteins in ovarian cancers are estrogen-regulated and could help identify patients who would benefit from endocrine therapy.” [i.e., anti-estrogen therapy])
- Letrozole effective in ovarian cancer, Raj Pandey K; Lancet Oncol. 2007 Aug;8(8):678.
- Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients, Smyth JF et. al.; Clin Cancer Res. 2007 Jun 15;13(12):3617-22 (“PURPOSE: To evaluate the efficacy of the aromatase inhibitor letrozole in preselected estrogen receptor (ER)-positive relapsed epithelial ovarian cancer patients and to identify markers that predict endocrine-sensitive disease. EXPERIMENTAL DESIGN: This was a phase II study of letrozole 2.5 mg daily until clinical or marker evidence of disease progression in previously treated ER-positive ovarian cancer patients with a rising CA125 that had progressed according to Rustin’s criteria. The primary end point was response according to CA125 and response evaluation criteria in solid tumors (RECIST) criteria. Marker expression was measured by semiquantitative immunohistochemistry in sections from the primary tumor. RESULTS: Of 42 patients evaluable for CA125 response, 7 (17%) had a response (decrease of >50%), and 11 (26%) patients had not progressed (doubling of CA125) following 6 months on treatment. The median time taken to achieve the CA125 nadir was 13 weeks (range 10-36). Of 33 patients evaluable for radiological response, 3 (9%) had a partial remission, and 14 (42%) had stable disease at 12 weeks. Eleven patients (26%) had a PFS of >6 months. Subgroup analysis according to ER revealed CA125 response rates of 0% (immunoscore, 150-199), 12% (200-249), and 33% (250-300); P = 0.028, chi(2) for trend. Expression levels of HER2, insulin-like growth factor binding protein 5, trefoil factor 1, and vimentin were associated with CA125 changes on treatment. CONCLUSIONS: This is the first study of a hormonal agent in a preselected group of ER-positive ovarian cancer patients. A signature of predictive markers, including low HER2 expression, predicts response.)
- The efficacy of tamoxifen in patients with advanced epithelial ovarian cancer, Karagol H et. al.; Med Oncol. 2007;24(1):39-43 (“BACKGROUND: Activity of tamoxifen as a salvage therapy in patients with advanced epithelial ovarian cancer was evaluated by a number of studies. In this study, we evaluated efficacy of tamoxifen in our patients with platinum-resistant epithelial ovarian carcinoma. … RESULTS: Twenty-nine eligible patients were included to the study. There were 1 (3%) complete response, 2 (7%) partial response, 6 (21%) stable disease, and 20 (69%) progressive disease. All patients were progressed after initiation of tamoxifen. Median progression-free survival was 4 mo (95% CI: 2.98-5.02). Disease progression of 19 (65%) patients were shown within the first 6 mo after initiation of tamoxifen. Progression-free survival was between 6 and 12 mo for 7 (24%) patients and > or =12 mo for 3 (10%) patients. The median survival after initiation of tamoxifen was 15 mo (95% CI: 7.2-22.8). No toxicity attributable to tamoxifen was seen in any of the patients. The only independent prognostic factor that had a significant predictive value for progression- free survival was the response to tamoxifen treatment (p = 0.043, hazard ratio: 0.12, 95% CI: 0.01-0.94). CONCLUSION: Considering minimal side effects and ability to cause objective responses, there is a place for tamoxifen in treatment of patients with platinum-resistant ovarian cancer. A phase III trial is required to confirm the value of the drug in patients presenting these clinical settings.”)
- Anastrozole therapy in recurrent ovarian adult granulosa cell tumors: a report of 2 cases, Freeman SA, Modesitt SC; Gynecol Oncol. 2006 Nov;103(2):755-8. Epub 2006 Jul 25 (“BACKGROUND: Ovarian sex cord stromal tumors are frequently hormonally active, and adult granulosa cell tumors often demonstrate estrogen receptor positivity. Thus, hormonal agents have been evaluated as potential treatments for advanced stage or recurrent adult granulosa cell tumors. CASE: Two cases of patients with recurrent adult granulosa cell tumors are presented. Each patient received multiple treatment modalities including chemotherapy and had previously progressed on leuprolide. Both patients were started on anastrozole with subsequent normalization of inhibin B levels and clinical exams. They have been maintained on treatment for 14 and 18 months, respectively, and have tolerated the drug without difficulty. CONCLUSION: Aromatase inhibitors may be a viable treatment option for women with advanced stage or recurrent ovarian adult granulosa cell tumors.”)
- Hormonal therapy in epithelial ovarian cancer, Rao GG, Miller DS; Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. (“The ovary is an endocrine and end organ. Hormones and their receptors have been associated with ovarian cancer and may be related to its causation. Some data suggest that hormonal therapies may have an effect on ovarian cancer in palliative settings. The most well studied anticancer drugs are tamoxifen, megestrol acetate, medroxyprogesterone acetate, leuprolide acetate, anastrozole and letrozole. Presently, no hormonal therapy is approved by the US FDA for the treatment of any type of ovarian malignancy or is listed as an active agent by any of the authoritative compendia. Owing to the endocrine associations with ovarian cancer, the minimal side effects of hormonal therapy and the demonstrated activity of hormonal therapies in other endocrine organ-associated malignancies, further study of hormonal therapies for ovarian cancer is warranted.”)
- Aromatase expression in ovarian epithelial cancers, Cunat S et. al.; J Steroid Biochem Mol Biol. 2005 Jan;93(1):15-24 (” … Aromatase activity was evaluated in ovarian epithelial cancer (OEC) cell lines by the tritiated water assay and the effects of third-generation aromatase inhibitors (AIs) on aromatase activity and growth were studied. Letrozole and exemestane were able to completely inhibit aromatase activity in BG1 and PEO14 cell lines. Interestingly, both AI showed an antiproliferative effect on the estrogen responsive BG1 cell line co-expressing aromatase and ERalpha. Aromatase expression was found in ovarian epithelial normal tissues and in some ovarian epithelial cancer cells and tissues. This finding raises the possibility that some tumors may respond to estrogen and provides a basis for ascertaining an antimitogenic effect of AI in a subgroup of ovarian epithelial cancers.”)
- Hormone therapy in epithelial ovarian cancer, Makar AP; Endocr Relat Cancer. 2000 Jun;7(2):85-93 (“Although epidemiologic studies, animal experiments and receptor studies have shown that not only normal ovaries but also many malignant ovarian tumors can be considered as endocrine related and hormone dependent, the place of hormonal therapy in the management of patients with ovarian cancer remains unsettled. Most trials of hormonal treatment in ovarian cancer have been retrospective, involved only limited numbers of patients, and lacked important patient-related data and information pertaining to tumor characteristics. In addition, a variety of hormonal preparations with different degrees of potency and in different dosages were included in these studies. A literature review shows that response to hormonal therapy even in a preterminal setting, is modest, with about 8% objective response but almost no side effects. In a similar patient setting, more toxic therapeutic agents do not yield a better response. The place of hormonal therapy in the management of patients with epithelial ovarian cancer needs more thorough evaluation in well-designed randomized trials.”)
Hello,
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
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Hi Kathie,
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
___________________________________________
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
H, Langdon SP. Antiestrogen therapy is active in selected ovarian cancer cases:
the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res.
2007 Jun 15;13(12):3617-22. PubMed PMID: 17575226.
15: Freeman SA, Modesitt SC. Anastrozole therapy in recurrent ovarian adult
granulosa cell tumors: a report of 2 cases. Gynecol Oncol. 2006 Nov;103(2):755-8.
Epub 2006 Jul 25. PubMed PMID: 16870240.
16: Rao GG, Miller DS. Hormonal therapy in epithelial ovarian cancer. Expert Rev
Anticancer Ther. 2006 Jan;6(1):43-7. Review. PubMed PMID: 16375643.
17: Lee EJ, Deavers MT, Hughes JI, Lee JH, Kavanagh JJ. Metastasis to sigmoid
colon mucosa and submucosa from serous borderline ovarian tumor: response to
hormone therapy. Int J Gynecol Cancer. 2006 Jan-Feb;16 Suppl 1:295-9. PubMed
PMID: 16515607.
18: Rao GG, Miller DS. Clinical applications of hormonal therapy in ovarian
cancer. Curr Treat Options Oncol. 2005 Mar;6(2):97-102. Review. PubMed PMID:
15717991.
19: Cunat S, Rabenoelina F, Daurès JP, Katsaros D, Sasano H, Miller WR,
Maudelonde T, Pujol P. Aromatase expression in ovarian epithelial cancers. J
Steroid Biochem Mol Biol. 2005 Jan;93(1):15-24. PubMed PMID: 15748828.
20: Papadimitriou CA, Markaki S, Siapkaras J, Vlachos G, Efstathiou E, Grimani I,
Hamilos G, Zorzou M, Dimopoulos MA. Hormonal therapy with letrozole for relapsed
epithelial ovarian cancer. Long-term results of a phase II study. Oncology.
2004;66(2):112-7. PubMed PMID: 15138362.
21: del Carmen MG, Fuller AF, Matulonis U, Horick NK, Goodman A, Duska LR, Penson
R, Campos S, Roche M, Seiden MV. Phase II trial of anastrozole in women with
asymptomatic müllerian cancer. Gynecol Oncol. 2003 Dec;91(3):596-602. PubMed
PMID: 14675683.
22: Bowman A, Gabra H, Langdon SP, Lessells A, Stewart M, Young A, Smyth JF.
CA125 response is associated with estrogen receptor expression in a phase II
trial of letrozole in ovarian cancer: identification of an endocrine-sensitive
subgroup. Clin Cancer Res. 2002 Jul;8(7):2233-9. PubMed PMID: 12114425.
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I used letrozole (Femara®) to treat recurrent malignant ovarian GRANULOSA CELL TUMOR.
The clinical improvement was very obvious. Malignant cutaneous fistule was closed and regression of size continue for 3 years. Unfortunately the patient died with complicated intestinal obstruction. To get better outcome letrozole should be used since earlier stages rather than reservation for recurrent conditions.
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Dear Professor Mohamed Nabegh El – Mahallawi MD., PhD., FRCOG,
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
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Good job Paul. This is a great post.
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