Breast cancer in women with recent exposure to fertility medications is associated with poor prognostic features.
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).


CONCLUSIONS
Breast tumors in women with recent FDT exposure present with poor prognostic features and share similarities with PABC. Survival is stage dependent.
Siegelmann-Danieli
Nava
N
Department of Hematology and Oncology, Geisinger Medical Center, Danville, PA 19822-2001, USA. nsdanieli@geisinger.edu
Tamir
Ada
A
Zohar
Hanna
H
Papa
Moshe Z
MZ
Chetver
Lika L
LL
Gallimidi
Zehava
Z
Stein
Moshe E
ME
Kuten
Abraham
A
D000328:Adult; D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology*; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000473:pathology*; D017697:Premenopause; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012307:Risk Factors; D016019:Survival Analysis
D005300:Fertility Agents, Female; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone