Serum testosterone levels and breast cancer recurrence

Abstract

Prospective studies show that high serum levels of androgens and estrogens are associated with increased incidence of postmenopausal breast cancer. The aim of the present analysis was to study the prognostic value of serum testosterone, estradiol and related factors in postmenopausal breast cancer patients. One hundred and ten patients without clinical recurrence were included in the study. After 5.5 years of follow-up, 31 patients developed distant metastasis (16), local relapse (4), or contralateral breast cancer (11). The risk of adverse events in relation to hormone level was examined by Cox' proportional hazard modeling, adjusting for hormone receptor status and stage at diagnosis. Body mass index and serum levels of testosterone, estradiol and glucose were significantly higher in patients who recurred than those who did not. The hazard ratios were 1.8 (95% CI ‫؍‬ 0.5-6.3) for the middle and 7.2 (95% CI ‫؍‬ 2.4 -21.4) for the upper tertiles of baseline testosterone distribution. Other hormones had only minor influence on prognosis. High testosterone predicts breast cancer recurrence. Further studies are required to determine whether dietary or other medical intervention to reduce testosterone can reduce the recurrence of breast cancer.Key words: breast cancer; recurrences; testosterone Prospective cohort studies on healthy volunteers who donated a blood sample at recruitment have shown beyond reasonable doubt that, after menopause, women with high serum levels of steroid sex hormones (both androgens and estrogens) are at increased risk of subsequent breast cancer. Testosterone and estradiol have similar predictive values, with relative risks of the order of 2-3 for women in the highest quintile compared to those in the lowest quintile of the hormone concentration. 1 Several anthropometric and metabolic determinants of high sex hormone availability have also been found associated with breast cancer risk, including obesity, especially abdominal obesity, 2 low serum levels of sex hormone-binding globulin (SHBG), 1 high levels of insulin, 3 fasting glucose and bioavailable insulin-like growth factor-I (IGF-I). 4 Oophorectomy and antiestrogenic treatment reduce breast cancer incidence 5,6 and the incidence of recurrence in breast cancer patients. 7,8 Several studies have also suggested that overweight, 2,9 weight gain during adjuvant treatment, 10 -12 hyperinsulinemia 13 and increased androgenic activity 14 -16 are associated with increased breast cancer recurrences. In the present study, we followed up women enrolled in a previous dietary intervention trial aimed at reducing sex hormone levels in postmenopausal breast cancer patients 17 to examine the relationship between serum hormone levels and cancer recurrence. Material and methodsOne hundred and fifteen postmenopausal women who were operated for breast cancer at least a year previously, not undergoing chemotherapy and with no clinical evidence of disease recurrence volunteered to participate in Diet and Androgens Trial-2 (DIANA-2), a dietary intervention ...

Metabolic syndrome as a prognostic factor for breast cancer recurrences

“…12 If the predictive value of metabolic syndrome is confirmed on larger series of patients, its evaluation shall become part of the standard diagnostic workup of breast cancer patients, and dietary or other medical intervention to prevent or control the syndrome should be considered. The present results however suggest that, to be effective, the correction of metabolic syndrome must be sufficient to obtain a substantial decrease in serum testosterone.…”

“…12 All patients signed an informed consent and the study was approved by the Institutional Review Board and the Ethical Committee of the Milan National Cancer Institute. Results on hormonal changes and the prognostic values of baseline hormone levels (testosterone, oestradiol and insulin) have been published elsewhere.…”

“…Results on hormonal changes and the prognostic values of baseline hormone levels (testosterone, oestradiol and insulin) have been published elsewhere. 12,17 The prognostic effect of metabolic syndrome more than 5.5 years after recruitment is now evaluated.…”

“…Results on hormonal changes and the prognostic values of baseline hormone levels (testosterone, oestradiol and insulin) have been published elsewhere. 12,17 The prognostic effect of metabolic syndrome more than 5.5 years after recruitment is now evaluated.The statistical analysis focused on the risk of breast cancer recurrence (local relapse, distant metastasis and contralateral breast cancer) in relation to the baseline presence of metabolic syndrome. The means of baseline hormone levels in patients with metabolic syndrome were compared with those of patients without metabolic syndrome.…”

“…Metabolic and hormonal parameters related to metabolic syndrome have been suggested to affect breast cancer prognosis too. [12][13][14][15] This is the first report addressing the issue whether breast cancer prognosis is affected by metabolic syndrome, defined by 3 or more of the following indicators: fasting glycaemia 110 mg/dl, HDL-cholesterol <50 mg/dl, triglycerides 150 mg/dl, waist circumference 88 cm, systolic pressure 130 mmHg and diastolic pressure 85 mmHg. 16 If confirmed, these results showing a significantly worse prognosis of patients with metabolic syndrome could have important implications for lifestyle intervention to prevent or decelerate cancer progression.…”