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Fertility Preservation Strategies for Breast Cancer Patients

Department Medical Oncology, National Cancer Research Institute, Genoa, Italy

Marco Venturini

Medical Oncology, Ospedale Sacro Cuore, Don Calabria, Verona, Italy

To the Editor:

Because American Society of Clinical Oncology (ASCO) recommendations do represent an important clinical practice guide for oncologists, the level of evidence underlying the recommendations itself in order to avoid implementation of unproven strategies is very important. The level of evidence of some ASCO statements on fertility preservation is questionable.¹ With regard to embryo cryopreservation as fertility preservation method, authors state that "for women with hormone-sensitive tumors (such as breast cancer) alternative hormonal stimulation approaches such as letrozole or tamoxifen have been developed to theoretically reduce the potential risk of estrogen exposure." However, many concerns arise about the safety for both women with breast cancer and babies born after this type of ovarian stimulation. Because of well-known potential biases, comparison of short-term breast cancer recurrence rates between patients who undergone the ovarian stimulation and nonrandomly assigned controls cannot be considered as the demonstration of the safety of the procedure for women with breast cancer.² Regarding the safety for the embryo, recent data indicate that babies born after treatment with letrozole for ovarian stimulation have a high risk of locomotor and cardiac malformations.³ Taking into account these concerns, the use of ovarian stimulation with letrozole should be discouraged instead of being considered as a potential option for women with breast cancer, as indicated in ASCO recommendations.

Regarding the strategy of ovarian suppression during chemotherapy in order to preserve the ovarian function, authors report that only "two small case series of 64 and 24 cancer patients without controls report resumption of menses and/or pregnancies after ovarian suppression." This statement is imprecise because, in breast cancer only, at least four phase II studies (not small case series) evaluated the activity of ovarian suppression with luteinizing hormone-releasing hormone analogs in preserving the ovarian function. These studies showed that this strategy is associated with a rate of ovarian function resumption ranging from 83% to 96%.^4-7 Two ongoing phase III studies will give definitive evidence of the role of luteinizing hormone-releasing hormone analogs in the ovarian function preservation.⁸

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: Further evidence on the safety and success of ovarian stimulation with letrozole and tamoxifen in breast cancer patients undergoing in vitro fertilization to cryopreserve their embryos for fertility preservation. J Clin Oncol 23:3858-3859, 2005[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. Fox KR, Scialla J, Moore H: Preventing chemotherapy-related amonorrhea using leuprolide during adjuvant chemotherapy for early-stage breast cancer. Proc Am Soc Clin Oncol 22:13, 2003 (abstr 50)

5. 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 Dugs 13:417-424, 2002[CrossRef]

6. 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 Treat 88:S229, 2004 (suppl 1; abstr 6028)

7. 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]

8. National Cancer Institute: Clinical trials: SWOG S0230 and GIM-6. http://clinicaltrails.gov/ct/show/NCT00068601 and http://www.clinicaltrials.gov/ct/show/NCT00311636

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