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In Reply

The Center for Reproductive Medicine and Infertility, Weill Medical College of Cornell University, New York, NY

Stephanie J. Lee

Fred Hutchinson Cancer Research Center, Seattle, WA

We appreciate the opportunity to respond to the comments by Del Mastro and Venturini because they illustrate the difficulties with the lack of high quality data (by guideline's standards) in the area of fertility preservation in cancer patients.¹ First, Del Mastro and Venturini question the use of letrozole for ovarian stimulation citing concerns about an increased relapse rate in women with breast cancer and higher malformation rate in babies. We agree that it is very important to track relapse rates when fertility preservation interventions are performed on women with hormonally sensitive tumors. However, no data thus far, albeit with a small number of treated patients, suggest a higher relapse rate.² The Fertility Preservation in Cancer Patients Guideline Panel strongly encourages additional studies and long-term follow-up of treated women so that better data are available to address these concerns. As far as letrozole causing congenital abnormalities when used for ovarian stimulation, the Biljan abstract³ referenced by Del Mastro and Venturini retrospectively compared 150 children born from infertile letrozole-treated women to approximately 36,000 children born after spontaneous conception. This study, which has not been published yet in a peer-reviewed journal, illustrates the difficulties in directly comparing the pregnancy outcomes of infertile and fertile women, where it is impossible to disentangle the factors causing infertility, infertility treatment differences, and consequences of assisted reproductive technologies. The infertile group was both older and had a much higher multiple birth rate than the general population, factors known to be associated with higher risks of fetal anomalies. Studies which compared letrozole-treated infertile women with those receiving clomiphene did not detect a higher malformation rate in the letrozole group.^4,5

Del Mastro and Venturini also assert that several phase II studies support the strategy of ovarian suppression during breast cancer therapy to preserve ovarian function. Two of these studies containing 24 and 64 patients were referenced in the Guideline.^6,7Another study was published in 2006 (n = 29) outside the timeframe of the review,⁸ and the fourth is an abstract (n = 25).⁹ All suffer from the inherent limitations of phase II studies without controls and none, with the exception of the study by Fox et al,⁶ used ability to conceive and live births as the end points. One of the points the Panel wishes to emphasize in the guideline is that preservation of menstruation does not guarantee retained fertility. In fact, in the abstract by Fox et al,⁶ spontaneous conception and pregnancy outcomes were suboptimal despite an 83% retention of menstruation. Nevertheless, because of the controversy, the panel strongly encourages randomized studies of ovarian suppression and specifically mentions the ongoing Southwest Oncology Group study.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Lee JS, Schover LR, Partridge AH, et al: American Society of Clinical Oncology Recommendations on fertility preservation in cancer patients. J Clin Oncol 24:2917-2931, 2006[Abstract/Free Full Text]

2. Oktay K, Buyuk E, Libertella N, et al: Fertility preservation in breast cancer patients: A prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol 23:4347-4353, 2005[Abstract/Free Full Text]

3. Biljan M, Hemming R, Brassard N: The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins. Fertil Steril 84:S95, 2005 (suppl 1)

4. Tulandi T, Martin J, Al-Fadhli R, et al: Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril 85:1761-1765, 2006[CrossRef][Medline]

5. Padte K, Padte JK, Gadkar J: Major congenital anomalies following conception with clomiphene versus letrozole. Proceedings of the 2nd Serono Symposia on Regulation of Follicle Development and its Clinical Implications Beaune, France, May 12-13, 2006, 2006 (abstr P-7)

6. Fox KR, Scialla J, Moore H: Preventing chemotherapy-related amonorrha using leuprolide during adjuvant chemotherpay for early-stage breast cancer. Proc Am Soc Clin Oncol 22:13, 2003 (abstr 50)

7. Recchia F, Sica G, De Filippis S, et al: Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast cancer: A phase II pilot study. Anticancer Drugs 13:417-424, 2002[CrossRef][Medline]

8. Del Mastro L, Catzeddu T, Boni L, et al: Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients. Ann Oncol 17:74-78, 2006[Abstract/Free Full Text]

9. Urriticoechea A, Walsh G, Rigg A, et al: Ovarian function protection with goserelin during adjuvant chemotherapy in pre-menopausal women with early breast cancer. Breast Cancer Res and Treatment 88:S229, 2004 (suppl 1; abstr 6028)[CrossRef]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Oktay, K. H. Articles by Lee, S. J. Search for Related Content PubMed Articles by Oktay, K. H. Articles by Lee, S. J. Social Bookmarking                            What's this?