L. V. A. M. Beex

STEROID HORMONE RECEPTOR ACTIVITY OF PRIMARY HUMAN BREAST CANCER AND PATTERN OF FIRST METASTASIS

SummaryA series of 258 breast cancer patients with known estrogen receptor (ER) status of the primary tumour who subsequently developed metastases were reviewed for site of first metastasis. In 188 cases progesterone receptor (PgR) data were also available.Univariate analysis showed metastatic patterns to differ statistically significantly related to ER status and (less pronounced) PgR status of the primary tumour. Patients with ER-positive tumours had bone metastases three times more often than patients with ER-negative tumours. With respect to PgR-positive and PgR-negative tumours this frequency differed by a factor of two. With regard to visceral metastases ER and PgR status were equally potent prognosticators, patients with receptor negative tumours having a 50% higher frequency of visceral metastasis than patients with receptor positive tumours. Assessment of metastatic patterns in relation to combined receptor status did not substantially enhance the discriminatory value of ER and PgR when assessed separately.Multivariate analysis showed that the observed differences in metastatic patterns were all attributable to differences in the ER status of the primary tumour, and were not influenced by age, menopausal status, axillary lymph node involvement, duration of disease-free interval (DFI), mode of postoperative treatment, or the PgR status of the primary tumour.

Human breast cancer: survival from first metastasis

SummarySurvival from the detection of first metastasis (SAM) was analyzed in a single center series of 258 patients with advanced breast cancer. During the 15 year period covered by this study 230 patients died, 215 of their disease. The overall median SAM was 28 months.Univariate analysis of SAM stratified by first dominant site of metastasis, estrogen receptor status (ER), progesterone receptor status (PgR), tumor size, axillary lymph node status, patient age, menopausal status, and disease-free interval (DFI) showed the first dominant site of metastasis, ER, PgR, and axillary lymph node status to be significantly associated with SAM. Patients with visceral metastasis as first dominant site of metastasis had significantly shorter survival than those with either bone or soft tissue metastasis, median SAM 16 vs. 34 vs. 41 months respectively (P<0.001). SAM also differed according to the steroid hormone receptor status of the primary tumor: median SAM 34 and 33 months for patients with ER-positive or patients with PgR-positive tumors against 14 months for patients with ER-negative or with PgR-negative tumors (P<0.001). Patients with axillary lymph node involvement at primary disease had a shorter SAM than those without, median SAM 24 vs. 35 months (P=0.006). No association between SAM and either tumor size, patient age, menopausal status, or DFI could be observed.Multivariate analysis including first dominant site of metastasis, ER, PgR, and axillary lymph node status showed the first dominant site of metastasis, ER, and axillary lymph node status to be independently associated with SAM.

Disease-free interval and estrogen receptor activity in tumor tissue of patients with primary breast cancer: analysis after long-term follow-up

SummarySpecific estrogen receptor activity (ER) was found in 115 of 175 (66%) tumors of patients treated for primary breast cancer in the period 1974–1981; 60 patients had ER-negative tumors. All patients were under observation for at least 48 months (median 76 months). The 24 patients who received adjuvant chemotherapy as part of their initial treatment, were excluded from the analysis of the disease-free interval (DFI). Groups of patients with ER-positive or ER-negative tumors did not differ significantly in clinical characteristics. Patients with ER-positive tumors had a significantly longer DFI than those with ER-negative tumors only in the first year after initial treatment. After prolonged observation a significant difference in recurrence rates was no longer found. In premenopausal women, the DFI was not different for those with ER-positive compared to those with ER-negative tumors, not even in the first year of observation. However, in postmenopausal women, those with ER-positive tumors had a significantly longer DFI up to 3 years after initial treatment but not thereafter. There was no difference in DFI between the ER-positive and ER-negative groups when the tumor stage was taken into account. It is concluded that the ER status of the primary tumor affects prognosis only on the short term.

Epidermal growth factor receptor and prognosis in human breast cancer: a prospective study

SummaryThe prognostic value of Epidermal Growth Factor Receptor (EGFR) in human breast cancer is a matter of debate. We conducted a prospective study that included 459 unselected patients with primary breast cancer (median follow-up 24 months) to assess the prognostic value of EGFR. EGFR was assessed using a standardized radioligand binding assay. Univariate analysis showed that EGFR is a factor indicative of a poor prognosis with respect to Disease Free Survival (DFS, P=0.03) and Overall Survival (OS, P=0.002), if an EGFR level of 50fmol/mg of membrane protein is introduced as a cut-off for EGFR-positivity. Multivariate analysis showed that EGFR was not an independent factor.This prospective study shows that EGFR, although not an independent factor, is indicative of poor prognosis in human breast cancer.

Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: the role of adjuvant chemotherapy

The prognostic significance of progesterone receptor activity (PgR) with regard to the estimated relapse-free survival (RFS) was studied in 350 one-center patients with primary breast cancer. All receptor assays were performed in one laboratory; PgR levels >10 fmol/mg protein were considered positive. Univariate as well as multivariate statistical analyses were used to examine the prognostic significance of several variables. Eighty-nine of the 350 patients received adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The median observation period was 69 months (range 12–125 months).In the group of 261 patients who did not receive adjuvant CMF, the PgR-status lacked prognostic significance; only the lymph node status significantly affected the RFS (p<0.00001). In contrast, in the CMF-treated group of patients, the PgR-status was the most powerful predictor of recurrence (p<0.0001). The menopausal and the lymph-node status increased the predictive value of PgR (p<0.001). Premenopausal CMF-treated patients with PgR+ tumors had a significantly longer RFS than those with PgR− tumors (p<0.02). The present data urge the need for a reappraisal of the prognostic significance of PgR and of the mechanism of action of adjuvant chemotherapy in primary breast cancer.

Concordance and discordance of estrogen and progesterone receptor content in sequential biopsies of patients with advanced breast cancer: Relation to survival

In 75 patients with advanced breast cancer, sequential biopsies were analyzed for estrogen receptor (ER). In 50 of these patients progesterone receptor (PgR) was also measured. All pairs of biopsies met the following criteria: (i) interval between the two biopsies: at least 6 weeks; (ii) biopsies performed at least 6 weeks after stopping endocrine therapy; and (iii) concordant histology. Discordance in ER was found in 14 of 75 patients (18.7%); PgR was discordant in 14 of 50 patients (28.0%). No significant differences were found between concordant and discordant groups of patients in age at first diagnosis, menopausal state, diameter of the primary tumor, time interval between the two biopsies and intervening therapy. The initial ER level in patients whose ER changed from positive to negative was significantly lower than in patients whose ER remained positive. PgR levels exhibited a rise only when ER rose at the same time. Sequential assays have increased the prognostic significance of ER and as a consequence the estimated survival time for patients whose tumors were ER-negative in both biopsies was significantly shorter than for patients whose tumors were ER-negative in only one of the two biopsies. We found no prognostic significance for PgR in either single measurements or repeated biopsies.

Steroid-hormone receptors in nonpalpable and more advanced stages of breast cancer. A contribution to the biology and natural history of carcinoma of the female breast.

Tumors of five groups of patients, with (1) nonpalpable primary breast cancer, (2) palpable operable primary breast cancer, (3) loco‐regionally advanced primary breast cancer, (4) first and (5) late metastatic breast cancer, were studied in respect to their steroid receptor content. A statistically significant decrease of progesterone receptor positive tumors and of tumors positive for estradiol and progesterone receptors, was found with increasing advance of the disease. A reversed extrapolation of these figures supports the hypothesis that every breast cancer contains steroid receptors and is hormone‐dependent from its inception.

Adjuvant chemotherapy in premenopausal patients with primary breast cancer; relation to drug-induced amenorrhoea, age and the progesterone receptor status of the tumour.

Adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil and methotrexate (CMF)-induced permanent ovarian suppression in 47 of 77 (61%) premenopausal patients with axillary node positive breast cancer. After a median observation time of 37 months the relapse-free and overall survival times were significantly longer for patients with permanent amenorrhoea. A strongly positive correlation between CMF-induced amenorrhoea and age of the patients, as well as between age and the tumour PgR status, was found. The induction of ovarian suppression predominantly occurs in patients with PgR positive tumours and may add an endocrine effect to the cytotoxic action of adjuvant chemotherapy in this particular group of older premenopausal women.