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Breast Cancer in Women With Recent Exposure to Fertility Medications is Associated With Poor Prognostic Features

From the Department of Hematology and Oncology (NS-D), Geisinger Medical Center, Danville, Pa, USA; Department of Community Medicine and Epidemiology (AT), Technion Institute of Technology and The Bruce Rappaport Faculty of Medicine, Haifa, Israel; Departments of Oncology (LLC, HZ, MES, AK, MZP) and Radiology (ZG), Rambam Medical Center, Haifa, Israel; and Department of Surgical Oncology at the Sheba Medical Center, Tel-Aviv, Israel.

Correspondence: Address correspondence and reprint requests to: Nava Siegelmann-Danieli, MD, Department of Hematology and Oncology, Geisinger Medical Center, Danvile, PA 19822-2001; Fax: 570-271-6542; E-mail: nsdanieli{at}geisinger.edu

Background: Fertility drug therapy (FDT) induces supraphysiologic endogenous estrogen production and might transiently increase breast cancer risk. Tumors developing following FDT exposure have not been extensively studied.

Methods: Thirty-eight breast cancer patients with 40 primary tumors and with history of FDT exposure were identified and compared with two other breast cancer groups: women with pregnancy-associated breast cancer (PABC, 22 patients with 23 tumors) and premenopausal women born during same calendar years and not exposed to hormonal manipulations or recent pregnancy (controls, 192 patients with 201 tumors). Patients were diagnosed and treated mostly during the last decade.

Results: Compared with controls, tumors of patients with FDT exposure presented at advanced stages (P < .005), were more likely to be estrogen or progesterone receptor negative (P < .03) and of poor histology grade (P <.0002). Aggressive features predominated among women diagnosed within 2 years of an FDT cycle (P <.05). FDT and PABC groups shared similarities. With a median follow-up of 43 months, relapse-free and cancer-free survival rates were significantly reduced in the FDT and PABC groups (P < .01 and P < .01, respectively). Multivariate analysis revealed only treatment-defined tumor stage (operable, locally advanced, or metastatic) as predictive of survival (P < .0001).

Conclusion: Breast tumors in women with recent FDT exposure present with poor prognostic features and share similarities with PABC. Survival is stage dependent.

Key Words: Breast cancer • Fertility • Clomiphene citrate • Human menopausal gonadotropins

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