Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer

Many studies have addressed the clinical value of pS2 as a marker of hormon e responsiveness and of cathepsin D (Cath D) as a prognostic factor in brea st cancer. Because pS2 and Cath D are both oestrogen induced in human breas t cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these protein s in breast cancer. A population of 1750 patients with breast cancer, inclu ding 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 wer e measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), f ollicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at th e day of surgery were used to define the hormonal phase in premenopausal wo men. There was a trend towards a higher mean pS2 level in the follicular ph ase compared with the luteal phase (17 ng mg(-1) and II ng mg(-1) respectiv ely, P = 0.09). Mean pS2 was lower in menopausal patients than in women wit h cycle (8 ng mg(-1) and 14 ng mg(-1) respectively, P = 0.0001). No differe nces in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels a nd negatively associated with FSH and LH, probably reflecting the link betw een pS2 and menopausal status. In premenopausal women, no association was f ound between pS2 and E2, Pg, FSH or LH levels. There were no correlations b etween Cath D level and circulating hormone levels in the overall populatio n. However, in the subgroup of premenopausal women with ER-positive (ER+) t umours, E2 was slightly associated with both pS2 and Cath D, consistent wit h oestrogen induction of these proteins in ER+ breast cancer cell lines. Th ere are changes in pS2 level in breast cancer throughout the menstrual cycl e and menopause. This suggests that the choice of the pS2 cut-off level sho uld take the hormonal status at the time of surgery into account. In contra st, the level of Cath D is unrelated to the menstrual cycle and menopausal status.