The effect of estrogen vs. combined estrogen-progestogen therapy on the risk of colorectal cancer

Studies suggest that estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) may have different associations with colorectal cancer (CRC) risk, but data are conflicting. Prior meta-analyses did not distinguish between ET and EPT. We conducted a meta-analysis to summarize the relative risks (RR) of CRC due to ET versus EPT among peri- or postmenopausal women. From a total of 2,661 articles, four randomized controlled trials, eight cohort and eight case-control studies were included. Variables assessed included study characteristics, duration and recency of menopausal hormone therapy (HT) use, method of assessment of HT use, outcome definition and its ascertainment method. RRs were synthesized by random-effects models. We found that EPT ever use was associated with a decreased risk of CRC (RR 0.74, 95% CI 0.68-0.81), and so was ET ever use (RR 0.79, 95% CI 0.69-0.91). While current use of ET was associated with a significantly reduced risk of CRC (RR 0.70, 95% CI 0.57-0.85), former use was not (RR 0.86, 95%CI 0.67-1.11). Recency did not significantly modify the association between EPT and CRC risk. EPT former use was associated with a lower RR of CRC compared to ET former use (p = 0.008) but no such difference was observed between EPT and ET current use (p = 0.12). Overall, we found consistent evidence supporting the association between EPT and CRC risk reduction, regardless of recency. While literature for the association between ET and CRC risk is heterogeneous, our analyses suggest only current use of ET is associated with a decreased CRC risk.     

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.     

The effect of age on estrogen and progesterone receptor in primary breast cancer

We evaluated the estrogen receptors (Er) and progesterone receptors (Pr) in 228 female patients with primary breast cancer by Dextran-Charcol method. Their ages vary from 30 to 91 years. Mean age 60.7 years. (SD: 13.6 years). Er mean was 70.31. (SD:103); there exists a statistically significant correlation between age and Er at p less than .001; older patients have higher Er. Pr mean was 60.73, (SD:128). There is statistically significant correlation between age and Pr at .01 less than p less than .025; older patients have higher Pr. There is also very statistical significant correlation between Er and Pr at p less than 0.1; when Er is high Pr is high.     

Nuclear binding of the estrogen receptor: A potential predictor for hormone response in metastatic breast cancer

We have previously described anin vitro immunohistochemical test employing anti-receptor antibodies, for demonstrating the nuclear binding characteristics of estrogen receptors (ER) in breast carcinomas. Based on a retrospective analysis of twenty-five patients with estrogen receptor-positive (ER+) breast cancer who were treated with hormone therapy and whose clinical responses were evaluable, we were able to demonstrate that this test may be valuable to predict which, among the ER+ tumors (whether or not they are progesterone receptor positive, PR+), are likely to respond to hormone therapy and which may fail. While tumors in which ER exhibited abnormalities in nuclear binding behavior (ligand-independent nuclear binding or no nuclear binding) failed hormone therapy (16 out of 19 patients), those in which nuclear binding of ER appeared normal (ligand-dependent) in thein vitro test, responded to hormone therapy (5/6 patients). While our previous report dealt with the procedural details, specificity of the reagents, and the design of the study, this report addresses the clinical aspects of this study and response correlation.     

激素受体与卵巢癌预后、发病机制及治疗的研究进展

卵巢癌作为恶性程度最高的妇科肿瘤,在肿瘤靶向治疗方面已取得了一定进展。激素疗法在乳腺癌治疗中的成功应用,使激素受体成为靶向治疗的首要研究方向。卵巢癌不同病理类型对激素的敏感性不同是激素疗法对卵巢癌治疗效果不同的根本原因。本文对卵巢癌激素受体的表达及其表达对预后的影响、发病机制的研究及临床治疗做综述。     

The effect of tumor size and axillary lymph node metastasis on estrogen and progesterone receptors in primary breast cancer

We evaluated the estrogen receptors (Er) and the progesterone receptors (Pr) in 209 female patients with primary breast cancer. There is statistically a very highly significant negative correlation between the size of the tumor and the Pr (p = 0.007); large tumor contains low Pr. The same correlation was found with Er, but it was not statistically significant (p = 0.40). There is also a negative correlation between the number of axillary metastatic lymph nodes and Er and Pr, but this was not statistically significant.     

Estrogen and progesterone receptor profile patterns in primary breast cancer

Summary Estrogen (ER) and progesterone receptor (PgR) analyses have been performed in 884 primary, malignant human breast tumor biopsies. Receptor contents were evaluated with respect to age and menopausal status. The frequency of ER + tumors was found to be significantly higher in postmenopausal than in pre/perimenopausal women. Age rather than menopausal status was found to be associated with this difference. The significant association with age was found in the post- but not the pre/perimenopausal women.The frequency of PgR + tumors was found to be significantly lower in the postmenopausal than in the pre/perimenopausal women. Neither age nor menopausal status alone could account for this difference, which appears to be due to a compound effect of the two factors.The distribution of receptor profile patterns is described according to menopausal status. The patterns differ significantly in pre- and postmenopausal women. PgR dominates in the premenopausal tumor while ER dominates in the postmenopausal tumor. This difference is apparent within the subgroup of ER + PgR + patients as well.The current tenets for prediction of recurrent disease utilizing steroid hormone receptor determinations are discussed for the group of ER + PgR + patients.sponsored by The Danish Cancer Society     

Steroid hormone receptor levels and adjuvant tamoxifen in early breast cancer

Summary Ten year disease-free survival (DFS) results of the Naples randomized trial of adjuvant tamoxifen (TM), 30 mg per day for 2 years versus no therapy according to receptor levels, are reported. From Feb. 1, 1978, through Dec. 31, 1983, 308 pre- and postmenopausal patients with early breast cancer entered the trial. Estrogen receptor (ER) data were available on 239 (77.6%) patients, progesterone receptor (PgR) data on 194 (63.0%), and both receptor data on 181 (58.8%).ER and PgR were assayed by dextran-coated charcoal technique in a single laboratory. The effect of adjuvant TM was significantly related to ER and PgR concentration of the primary tumor. The greatest TM benefit on DFS was evident in patients with the highest levels of receptors. The interaction between the treatment effect and receptor concentration was found whether ER and PgR were considered separately or together. Address for reprints: A. Raffaele Bianco, Division of Medical Oncology, University of Naples Medical School II, via S. Pansini, 5-80131 Naples, Italy     

Influence of the menstrual cycle on the concentrations of estrogen and progesterone receptors in primary breast cancer biopsies

Summary There is controversy in the literature regarding the effects of endogenous hormones on estrogen receptors (ER) and progesterone receptors (PR) in young women with breast cancer.We studied 117 young women with primary breast cancer and assessed their breast biopsies for ER and PR. The women had a record of their last menstrual period prior to breast biopsy. The menstrual cycle was divided into four phases — early proliferative (days 1–7), late proliferative (days 8–15), early secretory (days 16–22), and late secretory (days 23–30). There were lower levels of both ER and PR in biopsies excised during the early secretory phase than in other phases of the cycle; early proliferative phase receptor positive medians of ER = 77 fmol/mg protein and PR = 467 fmol/mg protein fell to ER = 28 fmol/mg and PR = 128 fmol/mg protein in the early secretory phase.     

Influence of endocrine status on biochemical and immunocytochemical estrogen and progesterone receptor assays in breast cancer patients

Summary Breast cancer tissue from 190 patients was studied for immunocytochemically reactive estrogen and progesterone receptors (ER, PR). Parallel cytosol ER and PR assays were performed on 159 of these patients using the dextran-coated charcoal (DCC) method. For the immunocytochemical determination, monoclonal antibodies to ER (ER-ICA kit) and PR were used in an immunoperoxidase procedure. Agreement between the two techniques in postmenopausal patients was better than in the premenopausal group (ER, kappa = 0.597 vs. 0.398; PR, kappa = 0.460 vs. 0.329). The median ER cytosol concentration in receptor-positive postmenopausal patients was significantly higher than in receptor-positive premenopausal patients (87 vs. 31 fmol/mg cytosol protein, p<0.001). A similar trend was also found in the immunocytochemical ER assay (270 vs. 207 histoscore units, p>0.05). Significantly higher cytosol ER contents were found in patients with low serum estradiol concentration. The proportion of ER-negative tumors was slightly higher in the premenopausal patients by both methods. In the PR assays (biochemical or immunocytochemical) there were no significant differences between the two patient groups in the proportion of PR-negative tumors or in the median PR content in PR-positive tumors.     

Rates for breast cancer characteristics by estrogen and progesterone receptor status in the major racial/ethnic groups

It has been reported that age-specific breast cancer rates vary by estrogen receptor and progesterone receptor status. We report breast cancer rates for age-at-diagnosis, stage-at-diagnosis, histological grade and type by estrogen (ER) and progesterone (PgR) receptor status in six major racial/ethnic groups. The average annual age-adjusted rates for breast cancers with estrogen receptor positive (ER⁺), ER^–, progesterone receptor positive (PgR⁺), PgR^–, ER⁺PgR⁺, ER⁺PgR^–, ER^–PgR⁺ and ER^–PgR^– are determined from 123,732 breast cancers with known ER status, diagnosed from 1992 to 1998 from 11 Surveillance, Epidemiology, and End Results (SEER) cancer registries. For each racial/ethnic group, their ER⁺ (ER⁺PgR⁺ and ER⁺PgR^–) age-specific rates increased with age (but at a slower pace after ages 50–54) while their ER^– (ER^– PgR⁺ and ER^–PgR^–) age-specific rates did not increase after ages 50–54. The rank orders of the rates among the racial/ethnic groups varied by ER/PgR status. The stage I rates were greater than the stage II rates for the ER/PgR groups except for ER^– and ER^–PgR^– cancers. The grade 2 (moderately differentiated) rates were greater than the grades 3 and 4 (poorly differentiated and undifferentiated cancers) rates for ER⁺ cancers, but not for ER^– cancers. These results suggest that although breast cancer is a disease with enormous heterogeneity, the multiple types of breast cancer can be separated into distinct subgroups by their ER status, and perhaps by their ER/PgR status, and their cancer characteristics may be important in understanding the multiple nature of breast cancer.     

Transferrin receptor is inversely correlated with estrogen receptor in breast cancer

Summary The transferrin receptor (TfR) has been identified as a marker for proliferation in cells in culture and can be accurately quantitated by specific radioimmunoassay. This study directly quantifies levels of TfR and compares them to levels of estrogen receptor (ER) and progesterone receptor (PgR) in biopsy material obtained from patients with infiltrating ductal carcinoma of the breast. A comparison of ER and TfR levels displayed an exponential distribution which was log-normalized to yield a linear inverse relationship (r = –.44). Although ER was strongly correlated with PgR, there was no correlation pattern between TfR and PgR. Multiple regression analysis indicated that 73% of ER levels could be predicted by a combination of the other two markers, PgR (representing degree of differentiation) and TfR (representing growth rate). Transferrin receptor levels were also found to be correlated (p<.05) with menopausal status, with tumors from premenopausal patients exhibiting higher levels, whereas the opposite pattern was shown for estrogen receptor levels (p<.02). Neither steroid receptor nor transferrin receptor levels were correlated to stage of disease or presence of nodal involvement. Addition of TfR level as an independent marker for proliferation may facilitate the decision-making process in the treatment of individual cases of carcinoma of the breast.     

绝经后乳腺癌雌、孕激素受体状态与血清性激素水平的关系

目的探讨绝经后乳腺癌雌激素受体(ER)、孕激素受体(PR)状态与患者血清性激素水平的关系及意义。方法使用全自动免疫分析仪化学发光分析法检测41例乳腺癌患者血清性激素六项(LH、FSH、PRL、E2、P、T)水平,免疫组化EnVision二步法检测乳腺癌ER、PR表达状态。结果绝经后乳腺癌PR阴性组与PR阳性组比较,患者血清LH、FSH水平显著增高(P值分别为0.005和0.031),PRL、E2、P、T水平在二组间差异无统计学意义;在ER阴性组与ER阳性组之间所测性激素水平差异无统计学意义。结论绝经后乳腺癌PR表达状态可能与垂体激素LH、FSH水平有关。     

激素替代治疗与女性肺癌关系的研究现况分析

肺癌是全球最常见的恶性肿瘤之一,在肿瘤致死原因中居第一位。女性激素替代治疗应用于卵巢功能衰退者以预防疾病、缓解症状。通过了解激素替代治疗应用现况及其与女性肺癌发生风险的研究发现,激素替代治疗可能增加、不增加甚至降低肺癌发生风险。近年来随着个体化给予低剂量的雌和(或)孕激素及新型激素的应用,使激素替代治疗更倾向于不增加肺癌发生风险。目前认为激素替代治疗不构成女性肺癌风险,在适宜人群中应用安全性高的激素,使适龄妇女在低风险的情况下获得最大收益。     

Influence of estrogen receptor variants on the determination of ER status in human breast cancer

Determination of estrogen receptor alpha (ER) status in breast cancer is an important predictive factor for clinical response to endocrine therapy. We have recently shown that discrepancies in ER status determined by immunohistochemical assay (ER-IHA) can occur between amino-terminal (1D5) and carboxyl-terminal (AER-311) targeted ER antibodies and that those tumors which demonstrate discordance are associated with increased expression of truncated ER variant mRNAs. In this study, we have explored this observation to examine if ER variant expression can exert a direct effect on ER-IHA or whether this association is attributable to the characteristics of the antibodies. ER negative cos-1 cells were transfected with expression vectors containing wild type ER (wt-ER) and/or a frequently expressed truncated variant, ER-clone-4 variant. We found that ER-IHA performed with the same N- and C-terminal targeting ER antibodies on cos-1 cells expressing wt-ER alone demonstrated no difference in signals by western blot (P>0.1). However, co-expression of wt-ER and the truncated ER-clone-4 variant, resulted in discordant IHA results with relatively higher ER-IHA H-scores from N-terminal antibodies (P<0.03). Furthermore, re-examination of a subset of breast tumors previously studied by ER-IHA showed persistent concordance in 4/5 cases and persistent differences in 3/5 cases with a different pair of ER antibodies. We conclude that the presence of truncated ER variant proteins can interfere with the interpretation of ER status determined by IHA and that this may account for some of the inconsistencies between ER status and response to endocrine therapy.     

Clinical significance of estrogen receptor β in breast and prostate cancer from biological aspects

Breast and prostate cancers are among the most common of all cancers. They are referred to as hormone‐dependent cancers, because estrogen and androgen are involved in their development and growth. The effects of these hormones are mediated by their respective receptors, estrogen receptor (ER) α and androgen receptor. Around 18 years ago, a second ER, ERβ, which has a very similar structure to ERα, was discovered. Its function has been investigated using a variety of methods and biological systems, leading to our present understanding that ERβ can interact with or inhibit ERα and androgen receptor function directly and/or indirectly, suppress cell growth, and influence responsiveness to endocrine therapy. In order to apply the “inhibition of cell growth” function to cancer treatment, several specific ERβ agonists have been synthesized and are being tested for effectiveness in cancer treatment. We need to keep our eyes on ERβ.     

Steroid receptor status difference in recurrent intracranial meningioma and breast cancer in the same patient

The authors report a case of multiple recurrent intracranial meningioma associated with breast cancer in a menopausal woman. High affinity estrogen (ER) and progestin receptors (PR) were assayed independently in the meningioma and the tumor. ER were found to be very low in the meningioma and high in the breast tumor. On the contrary PR were found to be high in the meningioma and could be not detected in the breast tumor. This unique case suggests that meningioma and breast cancer are not under the same type of hormonal influence.     

5758例女性乳腺癌激素受体状态及其相关因素分析

目的 探讨中国女性乳腺癌激素受体状态特点.方法 回顾性分析5758例女性乳腺癌患者的临床病理资料.结果 5758例患者中,雌激素受体(ER)阳性3692例,阳性率为64.1%;孕激素受体(PR)阳性4044例,阳性率为70.2%.单因素分析结果显示,女性乳腺癌的ER状态与患者的年龄、月经状态、T分期、N分期、腋窝淋巴结转移、组织学类型、组织分化程度有关,PR状态与患者的T分期、N分期、腋窝淋巴结转移、组织学类型、组织分化程度有关(均P＜0.05).Logistic多因素回归分析结果 显示,月经状态、T分期、N分期和组织分化程度是女性乳腺癌ER状态的独立影响因素,T分期、N分期和组织分化程度是女性乳腺癌PR状态的独立影响因素.结论 中国乳腺癌ER受体阳性率低于欧美等高发地区.女性乳腺癌的ER状态与月经状态、T分期、N分期和组织分化程度有关,PR状态与T分期、N分期和组织分化程度有关.