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

Abstract

Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast 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 proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg −1 and 11 ng mg −1 respectively, P = 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg −1 and 14 ng mg −1 respectively, P = 0.0001). No differences 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 and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status. 1999 Cancer Research Campaign

Trefoil Factor 1 in Early Breast Carcinoma: A Potential Indicator of Clinical Outcome during the First 3 Years of Follow-Up

“…Our finding that high TFF1 levels were related to premenopausal patients is in accordance with the findings of other studies 21, 41, although some opposite findings were also reported 32. Considering that middle-aged group (45-59 years old) consisted of both premenopausal and postmenopausal patients while all patients younger than 45 were premenopausal and all patients older than 59 were postmenopausal in our study, age of the patients was not analyzed as a continuous variable, but stratified into three age subgroups.…”

Cytosolic levels of TFF1/pS2 in breast cancer: their relationship with clinical–pathological parameters and their prognostic significance

“…Thus, it has also been reported that there is a highly significant correlation between the expression of TFF1 by primary tumors and their metastases [15], suggesting that this expression is constant along the tumoral progression. Other interesting finding in the present study has been the presence of higher TFF1 tumoral levels in premenopausal women than in postmenopausal ones, which has also been described in a prior study [16]. Considering that TFF1 is an estrogen-induced protein, this finding might suggest a possible influence of serum estrogen levels on the production of TFF1 by tumors.…”

Phenomapping of Patients with Primary Breast Cancer Using Machine Learning-Based Unsupervised Cluster Analysis

“…Furthermore, the observation of lower levels of pS2 in the older group could be justified by the fact that pS2-positive protein status has only been associated with ER-positive status in patients aged 50 years or less [ 51 ]. Indeed, previous studies showed that tumour pS2 concentration tends to be lower in postmenopausal patients [ 52 , 53 ], whereas cathepsin D tumour level does not show significant variation between pre- and postmenopausal patients [ 53 ]. The agreement between the literature evidence and the present study’s findings reinforces the capability of HAC in identifying strongly differentiated groups.…”