Effect of menstrual phase on surgical treatment of breast cancer

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

Section: Discussionmentioning

confidence: 99%

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

Pujol

et al. 1999

“…However meta-analysis of published studies has shown an overall significant effect of timing of surgery on both relapse-free and overall survival (Fentiman et al, 1994). Furthermore, a recent study showed that vascular invasion was observed in 47% of tumours excised between days 3 and 12 of the cycle but in only 33% of those undergoing surgery at other times (Badwe et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Body weight and vascular invasion in post-menopausal women with breast cancer

Fentiman¹,

Millis²,

Gregory³

1997

Summary To examine the relationship between body weight and vascular invasion (VI) around tumours in post-menopausal women with operable breast cancer, a retrospective study was conducted of 393 patients treated in a breast unit between 1987 and 1991. Weight was measured at the time of diagnosis. Vascular invasion was recorded as being present or absent. Vascular invasion was seen in slightly more of the 50 perimenopausal patients than in the 343 post-menopausal women (44% vs 36%). In the tumour specimens from post-menopausal patients weighing <50 kg, VI was observed in 11% compared with 45% of those weighing more than 80 kg (P = 0.02). Furthermore, the 5-year survival of those with VI was 74% compared with 91% for those without (P < 0.0001). Menopausal status and body weight may influence survival in patients with breast cancer, possibly as a result of the presence of unopposed circulating oestrogens at the time of surgery. Oestrogens may alter cohesiveness of breast cancer cells and modulate secretion of proteases, thereby influencing invasive potential.Excision of tumours in such an environment may have a deleterious impact on survival.Keywords: breast cancer; prognosis; weight; post-menopausal women; vascular invasionThe prognosis of women with operable breast cancer depends upon tumour type, axillary nodal involvement and also menopausal status (Adami et al, 1986;Caleffi et al, 1989). Premenopausal cases have the lowest hazard rates for relapse and death. Rates are intermediate in post-menopausal women and the highest rates are found in perimenopausal women, that is those within 5 years of last menstrual period (Langlands et al, 1989). The observed differences may be due to the different hormonal environment to which tumours are exposed in these three groups of women.Survival has been shown to be inversely related to body weight in the majority of studies (Boyd et al, 1981; Tartter et al, 1981;Newman et al, 1986;Tretli et al, 1990; Senie et al, 199 la;Vatten et al, 1991), but such a relationship is less obvious in premenopausal women (Greenberg et al, 1985). Although there is a relation between body weight and other prognostic factors, such as tumour size and axillary lymph node involvement, the effect of obesity remains an independent factor in multivariate analysis (Tarttar et al, 1981;Vatten et al, 1991). The mechanism through which menopausal status and body weight influence survival is uncertain, although it is known that most circulating oestrogens in postmenopausal women are derived from peripheral aromatization of adrenal androgens in subcutaneous fat. Thus, more obese women have higher plasma levels of oestrogens (Grodin et al, 1973).Additionally, the impact of obesity on survival is more pronounced among those women with oestrogen receptor-positive breast cancers (Verreault et al, 1989).The risk of relapse and death also depends upon the metastatic potential of the tumour as manifested by the presence of malignant Correspondence to: IS Fentiman cells in lymphatic channels and blood vessels (vascu...

“…Many hospitals are reluctant to adopt the approach of rescheduling operating times to accommodate the good phase of the menstrual cycle as defined by our previous data because of the opposing results that have been reported, and altering the timing of surgery to avoid days 3-12 may actually put the patient at risk. However, a recent meta-analysis of 21 published studies showed that timing of surgery had a significant effect, with an average 16% increase in overall survival in those operated on during the luteal phase of the menstrual cycle (Fentiman et al, 1994). The importance of timing of breast cancer surgery has been highlighted recently in an article in the Journal ofthe National Cancer Institute, which reported that several centres have emphasized the need for a prospective study (Anon.…”

Section: Resultsmentioning

confidence: 99%

Cell proliferation measured by MIB1 and timing of surgery for breast cancer

Cooper

Gillett²,

Smith³

et al. 1998

Summary We have investigated the use of the antibody MIBl as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIBl expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIBl scores between different phases of the menstrual cycle. Both MIBl score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.