Ronald G. Kay

Does delay in diagnosis of breast cancer affect survival

Summary1675 breast cancer patients in the Auckland regional area have been divided into two major groups according to delay in diagnosis greater or less than six weeks. Overall there is no difference in survival although the variables tumour size, skin attachment, and nipple retraction are more common in the group with longer delay, and grade III tumours in those with short delay. Three important prognostic variables (the presence of tumour steroid receptors, positive axillary nodes, and distant metastases at diagnosis) are equally distributed and have a similar effect on survival within the two delay groups. However, in a subgroup of women with negative axillary nodes, short delay is associated with poorer survival, independent of tumour size. More tumours with grade III histology and a negative progesterone receptor status are found in this subgroup. Thus, short delay may constitute a new prognostic variable of some importance when in association with negative axillary nodes.

Influence of height, weight, and obesity on breast cancer incidence and recurrence in Auckland, New Zealand

SummaryThe relationship between obesity and breast cancer has been investigated in 1281 Auckland breast cancer patients. Using a definition of obesity as a Body Mass Index (BMI) of ≥ 28 kg/m2, 179 (14%) breast cancer patients were classified as obese. The heights, weights, and BMI of 822 breast cancer patients aged 35–64 compared to 518 randomly selected Auckland women of similar age showed no significant difference. Within the breast cancer patients, there was no variation in nodal status or estrogen and progesterone receptor status between obese and non-obese women. However, tumours > 5 cm occurred significantly more often in obese patients. Time to recurrence was reduced in obese women with tumours ≤ 5 cm, no tumour in the axillary nodes, positive estrogen or progesterone receptor, and without metastases at the time of presentation of the disease. Although obesity has not been shown to influence breast cancer incidence, an effect on tumour recurrence is seen in patients with less advanced disease. This is similar to other reports which suggest that obesity is a weak but positive risk factor for recurrence.

Seasonal variation in breast cancer detection: Correlation with tumour progesterone receptor status

SummaryA significant circannual variation of the month in which patients detect the first sign or symptom of tumour has been defined in 1413 patients with breast cancer. The months of highest detection were in the late springearly summer, and lowest detection was in late autumn-early winter. Analysis of subgroups indicates that this cyclic trend was most significant in younger women with small or moderate-sized tumours containing steroid hormone receptors, particularly progesterone receptors. It seems likely that this variation is related to the effect of cyclic hormonal changes on tumour growth, possibly mediated through the pineal.

Season of tumour detection influences factors predicting survival of patients with breast cancer

SummaryThe rate of initial detection of breast tumours varies during the year in a seasonal fashion, more tumours being discovered in late spring/early summer than at other times of the year. This phenomenon is particularly pronounced in young women (< 50 years) with progesterone receptor positive tumours. The present study investigates whether season of tumour detection influences the predictive capacity of several recognised prognostic and risk factors in patients with breast cancer. Axillary nodal status, tumour progesterone receptor status, and season of tumour detection significantly influenced survival in both older (> 50 yrs) and younger (< 50 yrs) patients. Parity, lactational history, body mass index, tumour oestrogen receptor status, and patient age also influenced survival, but these effects were significant only in age groups < 50 or > 50 yrs. Season of detection of tumour did not affect the prognostic significance of axillary nodal status. However, the effect of oestrogen receptor status on survival was more significant in patients who detected their tumours in the spring/summer compared with winter (odds ratio 0.52 and 0.73 respectively). Negative progesterone receptor status was associated with significantly poorer survival only in patients with tumours found in the winter. There was a significant survival disadvantage for nulliparous compared with parous women with breast cancer who were ≥ 50 years at diagnosis, and for women who had never lactated compared with those who had lactated, but this disadvantage was restricted to those who found their tumours in the summer. An increased body mass index (≥ 28) was associated with decreased survival, but this was significant only for those detecting tumours in winter. The increased incidence of detection of breast cancer in spring/summer may reflect cyclic influences on tumour growth. Such influences may be hormonal in nature and may underlie the effect of season of tumour detection on the prognostic influence of lactation, parity, body mass index, and oestrogen and progesterone receptor status in patients with breast cancer.

The relationship of plasma 7α-hydroxy dehydroepiandrosterone to disease stage and adrenal androgens in breast cancer patients

Abstract The concentrations of 7 α-hydroxy dehydroepiandrosterone ( 7 α-hydroxy DHA) were measured in the plasma of patients presenting with different stages of breast cancer. The results were compared with the concentrations in control subjects and patients with benign breast disease. The concentrations of 7 α-hydroxy DHA in plasma were also compared with the concentrations of dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) in plasma. Plasma 7 α-hydroxy DHA was lower in patients presenting with early disease without axillary node involvement than in the control or benign disease groups but no significant difference was found between the control or benign disease group and the early disease nodal positive group or advanced disease groups. Plasma 7 α-hydroxy DHA was positively correlated with plasma DHA and, to a lesser extent, with plasma DHAS. The greater increases in plasma 7 α-hydroxy DHA compared to plasma DHA in patients presenting with distant metastases and with large tumours were significantly different to the control and benign disease group but there was no significant difference between the early disease groups and the control and benign disease group. The greater increase in plasma 7 α-hydroxy DHA compared to plasma DHAS in patients presenting with metastases was significantly different to the control group, but there was no significant difference in any of the other patient groups.

Estrogen receptor status, adrenal androgens and 7α-hydroxydehydroepiandrosterone in breast cancer patients☆

Plasma concentrations of dehydroepiandrosterone (DHA), DHA-sulphate (DHAS) and 7 alpha hydroxy-DHA (7 alpha OHDHA) were measured and compared with tumor estrogen receptor (ER) status in 33 postmenopausal patients with breast cancer. Although the plasma concentrations of DHA, DHAS and 7 alpha OHDHA were not different between the ER-positive (ER+) and ER-negative (ER-) patient groups, the ratios of 7 alpha OHDHA/DHAS and of DHA/DHAS were significantly higher (P less than 0.001 and P less than 0.001 respectively) in the ER- group. Nine women (normal or with benign breast disease) of similar age and menopausal status had values for plasma 7 alpha OHDHA/DHAS and DHA/DHAS between those of ER+ and ER- patient groups. The measurement of these steroid ratios in the plasma of breast cancer patients thus provides an indirect estimate of ER status. Since DHA and 7 alpha OHDHA are major metabolites of precursor DHAS in mammary tumor tissues, changes in their relative quantities in plasma may reflect the influence of receptor-mediated events on mammary steroid metabolism. Alternatively, the relative increase in tumor metabolism of androgens inferred from high 7 alpha OHDHA/DHAS and DHA/DHAS ratios in the ER- group may disrupt the hormonal microenvironment of the estrogen receptor. These events may, in turn, predispose toward ER status and a poor response to endocrine therapy.

Association between season of first detection of breast cancer and disease progression.

SummaryThe season of recurrence of tumour was investigated by follow-up of 1324 patients with breast cancer and compared with the season of initial tumour detection. Unlike primary tumours, where an increased incidence of detection has previously been observed in late spring and early summer, there was no significant seasonal variation in the time of recurrence. However, women with oestrogen receptor positive or progesterone receptor negative primary tumours recurred significantly more frequently in the same season that their primary cancer was initially detected. Overall there was an increased frequency of recurrence one year from diagnosis. Women <age 50 who initially found their tumour in winter or autumn had a significantly shorter disease-free interval before recurrence than those first detecting their tumour in summer or spring. This relationship was independent of nodal status and tumour size. Tumours initially detected in winter or autumn thus appeared to follow a more aggressive growth profile. This study indicates that the season of first detection of a breast cancer relates significantly to aspects of the future biologic behaviour of the tumour.

The relationship of urinary and plasma androgens to steroid receptors and menopausal status in breast cancer patients and their influence on survial

SummaryThe relationships between urinary 11-desoxy-17-oxo steroids (11-DOS), the ratio of 11-DOS to urinary 17-hydroxycorticosteroids (urinary discriminant ratio), plasma levels of the adrenal androgens dehydroepiandrosterone (DHA), DHA sulphate (DHAS), and 7α-hydroxy DHA (7αDHA), and tumour oestrogen receptor (ER) and progesterone receptor (PR) status were examined in pre, peri-, and postmenopausal women with breast cancer. Androgenic steroids and their metabolites decreased with age in women with breast cancer. In perimenopausal women there was a significant association of PR positive tumours and high androgen levels, whereas in postmenopausal women high androgen levels were associated with ER negative tumours. Survival was significantly related to plasma DHA level and tumour steroid receptor status. Thus, adrenal androgen levels below the group mean were associated with significantly decreased survival in women with postmenopausal receptor-positive tumours, and the association was particularly apparent in those who were axillary node negative. Since the number of patients studied was small these results should be regarded as provisional in nature. Nonetheless, the identification of this subgroup of node negative breast cancer women with reduced survival may be important when considering node negative patients for adjuvant therapy.