The relationship of body weight to response to endocrine therapy, steroid hormone receptors and survival of patients with advanced cancer of the breast

Abstract

Summary High body weight is associated with increased production of oestrogens which may influence the clinical behaviour of breast cancer. We have examined the influence of body weight on the response to endocrine therapy, steroid hormone receptor content and survival in 227 women who either presented with or developed advanced cancer of the breast. One hundred and thirty-three (59%) patients presented with operable disease and 94 (41%) with locally advanced tumours. Two hundred (88%) were treated by tamoxifen and 27 (12%) by ovarian ablation.High body weight was correlated with advanced tumour stage (P=0.002) and progesterone receptor (PR) positivity (P=0.01), but not with the presence of oestrogen receptor (ER P=0.21). The association between high body weight and PR positivity was particularly noticeable among ER positive tumours. There was no significant relationship between the nature of the response to therapy and weight (P=0.57). There was no significant difference in survival from the start of endocrine therapy (P=0.95), nor the time to progression of disease (P=0.29) between patients above and below the median weight of 64kg. Among the patients with operable disease, there was no difference in overall survival (P=0.42), relapse free survival (P=0.69), and survival from the start of endocrine therapy (P=0.85) according to body weight.Most epidemiological evidence suggests that high body weight and obesity are correlated with the incidence of breast cancer, particularly in postmenopausal women (Dewaard, 1982). Furthermore, these factors are generally associated with a worse prognosis (Papatestas et al., 1986;Abe et al., 1976;Eberlein et al., 1985;Greenberg et al., 1985;Tartter et al., 1981;Newman et al., 1986;Boyd et al., 1981), although one small study did not confirm this effect (Sohrabi et al., 1980). Similarly in mice, obesity and a fat enriched diet increase the incidence and speed of onset of mammary tumours (Waxler et al., 1979).In postmenopausal women the major source of oestrogens is the conversion of androstenedione, derived from the adrenal gland, to oestrone in body fat by the aromatase system (Cloncope, 1971;MacDonald et al., 1969). The strong correlation between the production of oestrone, the degree of this conversion and indices of obesity (e.g., weight, percentage of ideal weight and weight:height ratio) suggests that the excess production of steroid hormones within body fat which promotes the growth of mammary epithelial cells, may be the mechanism whereby there is an association between body weight and tumour incidence (Rizkallah et al., 1975; McDonald et al., 1978; Kirschner et al., 1982). This is supported by the report of lower levels of sex hormone binding globulin in the obese which may lead to higher levels of free oestrogens (Kirschner et al., 1982).Our working hypothesis for this study was that the greater endogenous production of growth promoting steroids in women of above average weight might override the effects of endocrine treatment and lead to a lower response rate and red...

The Possible Impact of Obesity on Androgen, Progesterone and Estrogen Receptors (ERα and ERβ) Gene Expression in Breast Cancer Patients

“…But this is not always the case, one possible explanation is that the increased estrogen levels in obese patients may stimulate tumor growth and adversely affect the prognosis. 17 The hormonal environment in obese women is consistent with the finding that obese women with breast cancer more frequently develop metastases and have a shorter survival time than non-obese breast cancer patients. 18 The reasons why breast cancer in obese patients is more frequently ER+/PR+ is unknown.…”

“…High body weight was correlated with advanced tumor stage (P = 0.002), but not with the presence of estrogen receptor (total ER P = 0.21). 17 Giuffrida et al presented findings from prognostic parameters of tumor evaluation as tumor size, presence of metastatic lymph nodes, tumor grade and histotype were available in 538 patients, no significant correlation by an overall F test from one-way analysis of variance was found between the patient BMI and any of these parameters. As with Giuffrida, in our study also there was no significant relation between BMI and tumor stage but obese individuals were in high stages and had a larger tumor size.…”

Triple‑negative breast cancer and its?association with obesity (Review)

“…Although a statistically significant association between obesity and recurrence or survival of breast cancer was demonstrated in some reports, others were unable to disentangle the effect of obesity from that of other potential factors, e.g., one study only investigated black and Caucasian women (90), whereas another only included women undergoing standard radical mastectomy, without other adjuvant therapy (91). However, several studies have directly pointed out that there is no association between obesity and survival or recurrence of breast cancer (92)(93)(94).…”

Body mass index, tumor characteristics, and prognosis following diagnosis of early-stage breast cancer in a mammographically screened population

“…(1, 6) However, other studies have observed no association between body mass and breast cancer prognosis. (12–18)…”