In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively). The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors. Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03). Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF. Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis. Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy. For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening. The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.
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