5-Fluorouracil (5-FU) is a commonly used adjuvant therapeutic
drug in treating
breast cancer.
5-FU is metabolically converted to 5-fluorouracil-2'-deoxyuridine-5'-monophosphate-(FdUMP) which is believed to inhibit
DNA synthesis in neoplastic cells by forming a tightly bound ternary complex with
thymidylate synthase (TS). In the present study, we examined the possible relationship between TS levels and clinico-pathologic and prognostic features in
breast disease. Mean TS levels of 2.9 pmol/g, 6.1 pmol/g, and 23.1 pmol/g were obtained in cases of benign
breast disease (3 cases), primary
breast cancer (115 cases), and recurrent
tumors (4 cases), respectively. In
breast cancer, mean TS levels significantly correlated with S-phase fraction (SPF),
DNA polymerase a and lymphatic invasion. Thus, TS levels in
breast cancer significantly reflected cell proliferation and
malignancy. Regarding the survival rate, patients with TS values above 10 pmol/g showed an unfavorable prognosis. The effectiveness of adjuvant
5-FU derivatives
chemotherapy was reflected in a higher disease-free survival rate in node (+) cases showing TS levels between 5 and 10 pmol/g (p < 0.1), but not in node (-) cases. In conclusion, TS levels in neoplastic tissues of the breast were highest in recurrent
tumors, followed by those in primary
cancer, benign
breast disease and in
breast cancer which reflected proliferative activity. Breast
cancers with extremely high TS levels were accompanied by an unfavorable prognosis; however, those with moderately high TS levels tended to respond to
adjuvant chemotherapy with
5-FU derivatives.