Prognostic implication of estrogen receptor content in breast cancer

Summary The cytosolic estrogen receptor (ER) content of the primary tumor was determined by isoelectric focusing in 170 consecutive women with unilateral breast cancer diagnosed in 1977 through 1980. No adjuvant treatment over and above surgery and radiotherapy was given. The overall corrected survival was not significantly (p>0.05) higher in ER-rich (<0.1 nmol/g DNA) than in ER-poor tumors, but the median period from recurrence to death was longer in the former (16 months) than in the latter (10 months) group. The difference in disease-free survival (DFS) in favour of the ER-rich tumors achieved its maximum — about 15% — after two years (p<0.01). At prolonged follow-up, however, the curves converged and there was no significant difference when the whole six year period of observation was taken into account. In patients without axillary metastases the same pattern emerged, with earlier recurrences in ER-poor tumors and a difference in DFS between the two ER groups at two years (p<0.01) which was diminished after five years (p<0.05). The ER content provided no significant prognostic information in patients with axillary node metastases or locally advanced disease.We conclude from the present and other available data that the ER content in breast cancer would seem to be an indicator of growth rate rather than of metastatic potential and accordingly a predictor of the pattern of recurrence and length of disease-free survival rather than of long-term survival.     

Prognostic role of estrogen receptor determination in breast cancer

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N- cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N- cases should be reconsidered.     

Prognostic significance of estrogen receptor determination in primary breast cancer

The authors report on 767 consecutive primary Stage I-II breast cancer cases followed-up from 3 to 8 years. The estrogen receptor (ER) content was determined in all cases and did not influence the treatment choice. A correlation was attempted between ER and menstrual or pathological nodal status (N) or the 5-year disease-free survival (DFS). ER was correlated with menopausal status ER+ cases being more frequent in postmenopausal patients, whereas no correlation was observed between ER and nodal status. In absence of nodal involvement (N-) the prognosis was not influenced by the ER status. A significantly better DFS was evident for ER+ respect to ER- patients in the N+ series but such a correlation is questionable as the adjuvant treatment (hormone or chemotherapy) given to such patients may have influenced the DFS according to the ER status. According to the present study, ER determination should not be used as a discriminant in the performance of adjuvant postoperative treatment based on a prognostic judgment.     

Prognostic effect of estrogen receptor status across age in primary breast cancer

Estrogen receptor (ER) status is considered as an important prognostic factor as well as a predictive factor for endocrine responsiveness in breast cancer. We analyzed the distribution of ER status across age and estimated variations in the prognostic impact of ER status related to patients' age and time since diagnosis. Overall, 26,944 patients with primary breast cancer diagnosed from 1989 to 2004 were included. The proportion of ER positive tumors increased over age from 51 to 82%. In multivariate analysis of overall survival, ER positive status was found to be a significantly positive prognostic factor over all age groups. This effect was limited to the first 5 years after diagnosis, RR: 2.08 (95% CI: 1.95-2.22, p < 0.0001). Overall survival during the following 5 years was slightly superior for women with ER negative tumors, RR of death: 0.89 (95% CI: 0.79-1.00, p = 0.049). Results were unchanged in patients who did not receive adjuvant systemic therapy (n = 6,272). Thus, positive ER status does not confer a negative impact on survival in young women as has been previously reported. The inferior prognosis for ER negative patients during the first 5 years after diagnosis changes into a slightly superior residual prognosis compared to ER positive patients independent of use of adjuvant systemic therapy. This may have an impact on future designing of guidelines for adjuvant endocrine therapy beyond 5 years.     

Prognostic value of estrogen and prolactin receptor analysis in human breast cancer

Hormone receptors for estrogen (ER), progesterone (PGR) and prolactin (PRL-R) were measured in primary breast cancer tissues obtained from 214 patients at radical mastectomy. The patients were followed up at intervals of one to three months to examine the relationship between hormone receptor status and prognosis. ER status was related to PGR status but not to PRL-R status. PRL-R was more frequently detectable in pathologic stage 3 than in stage 1 & 2 (22% vs. 10%, P less than 0.05) whereas ER and PGR were not different between stage 1 & 2 and stage 3 groups. The influence of receptor status on prognosis was analyzed in 164 patients of stage 1 & 2 by means of the actuarial life table technique. The recurrence-free interval was not related to ER, PGR or PRL-R status. The ER-positive group was associated with significantly prolonged survival compared with that of ER-negative patients at 42 to 51 months after surgery. PRL-R positive patients had a significantly worse survival than the PRL-R negative group (P less than 0.05). These findings indicate that receptor status may provide useful prognostic information in patients with early breast cancer and that the lactogenic hormone may play an unfavorable role in relation to the prognosis of human breast cancer.     

Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer.

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.     

Prognostic impact of early detection of contralateral primary breast cancer

The authors report on a consecutive series of 175 contralateral metachronous breast cancers. Eighty-six cases detected in women self referring for cancer-related subjective symptoms were compared to 89 cases detected as asymptomatic at routine examination. Detection in the asymptomatic phase was associated with a more favorable stage, but no differences in survival rates were observed between asymptomatic or symptomatic cancers when survival was measured from the date of first cancer diagnosis, in order to adjust for lead time bias. The nodal status of the first or of the second cancer was the only variable of prognostic value on univariate analysis, whereas a significant association to prognosis was evidenced only for nodal status of the first cancer. The study suggests that routine clinico-mammographic check-up may achieve early detection of contralateral metachronous breast cancer in the asymptomatic phase, but this does not seem to have a relevant impact on prognosis. The occurrence of a second primary breast cancer seems to be an indicator rather than a determinant of a worse prognosis.     

Variation in the risk of radiation-related contralateral breast cancer by histology and estrogen receptor expression in SEER

Radiation exposure, particularly at a young age, is an established cause of breast cancer. It is not known whether radiation-related breast cancer risk varies by molecular subtype. We characterized the relative risk (RR) of contralateral breast cancer (CBC) related to radiotherapy by histology and estrogen receptor (ER) status of the CBC in five-year survivors in the Surveillance, Epidemiology, and End Results database using Poisson regression models adjusted for attained age and calendar year, age at and year of treatment, ER status of the first breast cancer, and disease stage. 205,316 female breast cancer survivors were followed for an average of 10 years from 1973 until 2007, during which time 6924 women developed a subsequent primary invasive breast cancer in the contralateral breast. The overall RR (and 95% confidence interval (CI)) of radiotherapy-related CBC was 1.11 (1.05–1.16). There was no heterogeneity in risk according to histology of the CBC (P > 0.50) for all ages or young age at exposure, but case numbers were small for subtypes other than ductal and lobular carcinomas. Information on ER status was available from 1990 onwards for 3546 CBC cases, of which 2597 (73%) were ER+ and 949 (27%) were ER−. The RRs were 1.10 (1.02–1.19) for ER+ CBC and 1.19 (1.04–1.35) for ER− CBC (P _difference = 0.33). Among women treated age <35 years, radiation-related risk of CBC was non-significantly elevated for ER− (RR = 1.38, 95% CI: 0.96–1.97) but not for ER+ tumors (RR = 0.80, 95% CI: 0.47–1.35) (P _difference = 0.09). We did not find clear evidence that radiation-related risk varies by histology or ER status, but our findings, which were the first to examine this question, were suggestive of possible differences by ER status that may merit further investigation.     

Prognostic value of estrogen receptors in primary breast cancer.

The estrogen receptor status in 335 primary breast carcinomas was correlated with disease-free interval, survival and site of recurrent disease. Estrogen receptor positive carcinomas had a longer disease-free interval, a longer survival (mastectomy-death) and a longer time interval between recurrence and death. These parameters were also influenced by the lymph node status at mastectomy. Estrogen receptor positive cancers had a significantly better chance of survival independent of lymph node status. Estrogen receptors also delayed recurrence in node-positive carcinomas, but this advantage gradually disappeared with increasing interval after mastectomy. Estrogen receptor positive or estrogen receptor negative primary carcinomas did not show any predilection for spread to any particular site.     

Prognostic impact of the early detection of metachronous contralateral breast cancer

The study aimed to assess whether the early detection of asymptomatic metachronous contralateral breast cancer (MCBC) improves the prognosis of the patient compared with a diagnosis at symptomatic onset. We reviewed 339 MCBC cases that were consecutively diagnosed from 1970 to 2001, for which reliable information on subjective symptoms was available. The association of early (asymptomatic vs. symptomatic) detection with mortality from breast cancer was studied by univariate and multivariate analyses, adjusting for potential confounders. A more favourable stage at diagnosis was evident for asymptomatic vs. symptomatic MCBC (pT1=84.2% vs. 58.1%, pN0 65.0% vs. 52.4%). The hazard ratio (HR) of breast cancer death was approximately half (0.49%, 95% Confidence Interval (CI) 0.29-0.83, P = 0.008) for asymptomatic vs. symptomatic MCBC. Although length bias may have occurred (symptomatic MCBC had a shorter free interval from the first cancer), the present evidence supports the practice of active follow-up aimed at the early detection of asymptomatic MCBC.     

Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients.

PURPOSE: The role of transforming growth factor beta (TGF-beta) in breast cancer is ambiguous; it can display both tumor suppressing and enhancing effects. Activation of the TGF-beta signal transduction system is subject to hormonal regulation. This study was conducted to further analyze the role of TGF-beta receptors in breast cancer and to evaluate their significance as prognostic markers. EXPERIMENTAL DESIGN: Expression of TGF-beta receptor I (TbetaRI) and TGFbeta receptor II (TbetaRII) was retrospectively analyzed by immunohistochemistry in 246 breast cancer patients. RESULTS: Expression of TbetaRI was strongly correlated with tumor size (P < 0.001) and nodal status (P = 0.012) but only weakly with overall survival (P = 0.056). In contrast, TbetaRII was prognostic for overall survival in univariate analysis (P = 0.0370). In estrogen receptor (ER) -negative patients TbetaRII expression was correlated with highly reduced overall survival (P = 0.0083). In multivariate analysis TbetaRII proved to be an independent and highly significant prognostic marker with a hazard ratio of 6.8. Simultaneous loss of both ER and TbetaRII was associated with longer overall survival times comparable with those of ER-positive patients. CONCLUSIONS: The results of this exploratory study show that TbetaRII is an independent, highly significant prognostic indicator for overall survival in ER-negative patients. In addition our results are supportive of a mechanism of breast cancer progression in which a selective loss of the tumor inhibitory action of TGFbeta takes place, whereas tumor- promoting aspects remain intact.