Hormone receptor status of breast cancer in India: a study of 798 tumours

The objectives of this study were to document the oestrogen and progesterone receptor (ER & PR) status of breast cancer in the Indian population (as done by immunohistochemistry on paraffin blocks), and correlate the steroid receptor status of breast cancer with all relevant patient and tumour characteristics. Our current data have been compared with previously published data from other centres. In contrast to the higher rates reported in the Western literature, only 32.6% of our tumours were ER positive and 46.1% were PR positive. Tumours were separated into four categories: ER+PR+ (25%), ER+PR- (7.4%), ER-PR+ (21.1%) and ER-PR- (46.5%). ER and PR immunoreactivity increased with advancing age, and correlated with the presence of elastosis. Infiltrating lobular carcinoma, mucinous carcinoma, and mixed tumours were more frequently ER & PR positive. High-grade infiltrating duct carcinomas, pure comedo ductal carcinoma in situ, and medullary carcinoma were predominantly ER & PR negative. The presence of necrosis and lymphovascular invasion showed an inverse relationship with ER and PR reactivity.     

Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: age-specific prevalence and survival

BACKGROUND: Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B. OBJECTIVES: To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women. DESIGN: A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+). OUTCOME MEASURES: We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like, and (11.6%) Her-2/neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group <35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%, 14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the <35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome. CONCLUSIONS: The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged <35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients.     

A multifactorial analysis of steroid hormone receptors in stages I and II breast cancer.

It has been shown that the level of estrogen receptors (ER), and to some extent progesterone receptors (PR), correlate to a high degree to the response to endocrine therapy in advanced breast cancer patients. To evaluate the prognostic value of ER/PR in early breast cancer, 80 patients with stages I and II were studied. They all underwent modified radical mastectomy. Patients with stage I disease (negative LN) received no further treatment, while those with stage II received standard adjuvant chemotherapy. All the patients were followed for 4 years. The ER and PR were measured in each primary tumor by the glycerol density gradient method. Values of 10 fmole/mgm protein or greater were considered positive (+) and less than 10 fmole/mgm were considered negative (-). The results revealed: (1) Fifty-two patients (65%) had ER+, of which 44 (85%) were also PR+; 28 patients had ER-, of which 24 were also PR- (p less than 0.0001). (2) ER/PR correlated with age as 71% of the patients over age 50 had ER+/PR+, compared to 33% of those under age 50 (p less than 0.05). (3) Postmenopausal patients had a higher incidence of ER+/PR+. (4) Primary tumors less than 2 cm in size had higher ER+; 71% in those with stage I and 80% in stage II. (5) Fifty-eight per cent (38) of patients with ductal carcinoma had ER+/PR+, compared to 67% (4) with lobular carcinoma. (6) The disease-free survival of patients with ER+ tumors was significantly longer than those with ER- tumors (p less than 0.005) both in positive and negative LN patients. The same was true for PR+ compared to PR- (p less than 0.005), but only in those with stage II disease. The overall survival rates were similarly significant in favor of ER+ and PR+ patients (p less than 0.025), but only in stage II disease. It seems that the status of steroid hormone receptors has a major prognostic factor second only to the LN status.     

Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 ≥ 14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies.     

Prognostic factors in breast cancer and the development of a prognostic index

A number of different factors are known to be correlated with survival of patients with breast cancer. Among these are lymph node status, tumour size, oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) status. The purpose of this study was to investigate the relative significance of these factors and use this information to construct a prognostic index capable of predicting survival. These factors together with age and menopausal status were studied and correlated with prognosis in 796 women with primary breast cancer. The data were analysed in a stepwise manner by the Cox proportional hazards regression technique. Statistically, greater than 3 nodes involved gave the worst prognosis (P less than 0.001). This was followed by ER if less than 10 fmol/mg cytosol protein (P less than 0.001), PR if less than 10 fmol (P less than 0.01), greater than 0 lymph nodes involved (P less than 0.01) and the number of years over age 65 (P less than 0.01). When these factors were accounted for, tumour size, menopausal status and AR did not significantly improve prediction of survival. The significant factors were incorporated into a prognostic index: I = N + E + P + A, where N = 0 if no nodes involved, 13 (if 1-3 nodes involved and 31 if greater than 3 nodes involved, E = 15 if ER less than 10 fmol, P = 12.5 if PR less than 10 fmol and A = number of years over 65. Using this index five year survival curves were constructed corresponding to groups of patients with widely differing prognoses. Predicted five year survival ranged from 96 to 12 per cent.     

Breast hormonal receptors test should be repeated on excisional biopsy after negative core needle biopsy

Therapeutic decision-making for women diagnosed with breast cancer requires accurate determination of the estrogen receptor (ER) and progesterone receptor (PR). Decisions about adjuvant therapy are often based on the immunohistochemical (IHC) profile of the core needle biopsy sample (CNB) because the staining is not repeated on the final excisional biopsy (EB). The purpose of this study was to assess the concordance of breast cancer IHC receptor assays on CNB and EB. We identified 176 patients with matching breast CNB and EB that had available ER and PR. While the CNBs were processed and stained in different laboratories, the EB were processed and stained in our institution. The following antibodies were used 1D5, 6F11 and SP1 for ER, and PgR636, 16 and 1E2 for PR, from Dako, Leica and Ventana respectively. Correlation of scores of CNBs with matching EB was analyzed using Spearman correlation coefficients. Sensitivity, specificity, overall agreement and the kappa statistic were used to measure the concordance between CNB and EB. For CNB, there were 141 (80.1%) cases positive for ER and 118 (67%) cases positive for PR. For EB, there were 143 (81.3%) cases positive for ER and 130 (73.9%) cases positive for PR. Overall agreement for ER and PR was seen in 93% (95% CI = 0.88, 0.96) and 90% (95% CI = 0.84, 0.94) respectively. Overall, ER- CNB/ER+ EB was seen in seven (4%) cases and PR- CNB/PR+ EB in 15 (8.5%) cases. ER+ CNB/ER- EB was seen in five (2.8%) cases and PR+ CNB/PR- EB in three (1.7%) cases. To avoid erroneous omission of life-saving endocrine therapy ER and PR should be repeated on the EB for patients whose CNB has negative hormonal receptors.     

The oestrogen-progesterone receptor ratio: an indicator of breast cancer evolution

Two groups of patients were chosen from among 4,025 subjects examined in a breast screening program, one consisting of patients with stage I and the other of patients with stage IV breast cancer, characterized by neoplastic recurrence. In this comparison p53, HER and grading are of no direct help. We investigated receptor status at the time of the first operation and after complete surgical excision of the recurrence. The following variables were determined: oestrogen and progesterone receptor measures (ER, PR) in f.mol/ml, the 4 receptor phenotypes, the oestrogen-progesterone ratio and histological tumour grading in relation to oestrogen receptor positivity or negativity. Surgery consisted in quadrantectomy or total mastectomy, with axillary dissection or complete surgical excision of the recurrence. Adjuvant therapy was administered. The results show a different receptor percentage in recurrence compared to early breast cancer, which though not significant, indicates a reduced presence of ER+ PR+, ER- PR-, and an increase in the ER+PR- phenotype. Recurrence occurs more frequently when the lesion at the first operation is more advanced and if radiotherapy has not been included in the treatment. Histological grading shows a greater number of undifferentiated cells and a reduction in ER+ in recurrence, thus indicating a reduced target for the most widely used hormone treatments. The oestrogen-progesterone ratio is significantly increased (P < 0.01) in recurrence compared to stage I cancers. The cause of recurrence is a neoplastic embolism, often documented histologically. Recurrence does not necessarily mean a poor prognosis, because there is a survival rate after two years of 77% of the cases treated. These results obtained with widely used methods show the aggressiveness of some breast tumours, which can evolve and have a very poor prognosis even with the most complete therapy.     

Relationship of estrogen and progesterone receptors to prognosis in breast cancer.

To ascertain the role of estrogen (ER) and progesterone (PR) receptors as prognostic indicators of resectable breast cancer, the records of 204 patients were analyzed whose receptor studies were done at the Maimonides Medical Center from 1975 to 1983. All patients had radical or modified radical mastectomies and did not show any evidence of distant metastases at the time of operation. Median follow-up was 37 months. An additional 117 patients received some form of adjuvant therapy, mainly chemotherapy, and were analyzed separately. Life table analysis using the log rank test for measuring significance, and a Cox multivariate analysis was performed. At 48 months, 22% of the ER positive (ER+) group versus 33% of the ER negative (ER-) group had recurred as compared to 16% and 35% for the PR+ versus PR- groups, respectively. Life table analysis of the disease free interval (DFI) showed that the difference between the ER+ and ER- groups was not significant (p greater than 0.1), while the difference in DFI between the PR+ and PR- groups was significant (p less than 0.05). Multivariate analysis revealed that the most important factors in predicting the DFI were nodal status (p less than 0.001), tumor size (p less than 0.025), and progesterone receptor status (p less than 0.05). Estrogen receptor status was not found to be significant. In conclusion, PR- patients have a shorter DFI than PR+ patients and that PR status is a more valuable predictor of DFI than ER status.     

Prognosis of Japanese Breast Cancer Based on Hormone Receptor and HER2 Expression Determined by Immunohistochemical Staining

BACKGROUND: We classified Japanese breast cancer patients based on estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression and compared their prognoses. METHODS: We compared the background and prognostic factors of 600 patients with breast cancer who were assigned to the following groups: luminal A (ER + and/or PR + and HER2-; n = 431; 71.8%), luminal B (ER + and/or PR + and HER2 + ; n = 27; 4.5%), HER2 (ER-, PR-, and HER2 + ; n = 39; 6.5%) and basal-like (BBC; ER-, PR-, and HER2-; n = 103; 17.2%). RESULTS: Background factors did not significantly differ among the groups. Disease-free survival rates were significantly lower for the luminal B, HER2, and BBC subtypes than for the luminal A subtype. Cancer tended to recur earlier and overall survival was significantly lower for the BBC than for the luminal A and HER2 subtypes. Overall survival rates for the luminal B, HER2, and luminal A subtypes were comparable. CONCLUSIONS: The subtype distribution for Japanese and Caucasian patients was comparable. The prognosis for the BBC subtype was poorest among all subtypes. Breast cancer tended to recur earlier for the luminal B and HER2 subtypes than for the luminal A subtype; however, overall survival did not significantly differ among them.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy

The molecular subtypes of breast cancer based on status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression are associated with markedly different clinical outcomes. We retrospectively analyzed 774 breast cancer patients with four or more positive nodes, who underwent mastectomy between March 1999 and December 2007. Treatment with postmastectomy radiotherapy (PMRT) reduced the rates of locoregional recurrence-free survival (LRFS; 6.7% vs. 26.6%), distant metastasis-free survival (DMFS; 26.9% vs. 50.0%), and mortality (24.4% vs. 45.3%) for luminal-A subtypes (ER+ or PR+, Her2-) and reduced LRFS (12.1% vs. 27.5%) for the luminal-B subtype (ER+ or PR+, Her2+) compared with patients not receiving PMRT. However, PMRT did not affect the endpoints for the Her2-enriched or basal subtypes. Thus, understanding the differences in patterns of relapse between the different subtypes of breast cancer may enable targeted adjuvant therapy and improved surveillance decisions.     

Steroid Hormone Receptor Profile of Normal, Benign, and Malignant Female Breast Epithelium: An Immunohistochemical Analysis of 325 Biopsies

Abstract: The steroid hormone receptor (SR) profile was determined for both the estrogen receptor (ER) and progesterone receptor (PR) in 55 fibroadenomas, 69 fibrocystic changes, 38 ordinary, and 14 atypical intraductal hyperplasias as well as 149 breast carcinomas obtained from 325 female patients by diagnostic surgical biopsy. Normal breast tissue adjacent to the lesions under study was simultaneously evaluated in 234 cases. SR were proven immunohistochemically in cryostat sections using an immunohistochemical assay with rat monoclonal antibodies against human ER or PR. The findings were scored and summarized into the phenotypes ER+PR+,ER?PR+, ER+PR? and ER?PR?. The ER+PR+ status was most often found in fibroadenomas (67%) and normal breast tissue (64%) as well as in fibrocystic changes (63%) and breast carcinomas (58%). ER?PR? was inversely rare in fibroadenomas (4%), normal breast tissue (15%), fibrocystic changes (23%), and breast carcinomas (29%). The simultaneous SR analysis in breast disease and its surrounding normal tissue showed in fibroadenomas in 90% and in fibrocystic changes in 80%, a ER/PR phenotype expression similar to adjacent normal tissue; whereas in breast carcinomas the SR status corresponded with the preexisting normal tissue only in 36%. The comparative SR analysis of normal and pathological breast tissue showed a gradually inverse biological correlation between the decrease of ER+PR+ and the increase of ER?PR? frequency from benign breast changes to noninvasive and invasive breast carcinomas. In benign breast epithelium, ER?PR+ might be regarded as low-risk phenotype, whereas ER+PR? could be estimated as high-risk phenotype in view of a later dedifferentiation and possible malignization. The more frequent discordance of SR expression between breast carcinomas and their adjacent normal breast tissue suggests that the neoplastic growth may become more and more independent from normal endocrine influences.     

Renal cancer steroid receptors: biochemical basis for endocrine therapy.

Estradiol receptor (ER) and progesterone receptor (PR), found in experimental renal cancer as well as in normal human kidney and in human renal cell carcinoma (RCC), have been measured in 27 RCCs from patients submitted to surgery and endocrine therapy in an attempt to predict the response to progestational therapy. Of these 27 tumors 59% were positive for ER and 59% for PR; 37% were positive and 19% negative for both ER and PR. The follow-up of 23 patients showed that progestational therapy, started in 18 patients, has given favorable results in 14 patients and negative results in 3 patients with ER-PR- renal cancer. Antiestrogenic therapy, started soon after nephrectomy in 1 patient with ER+PR- renal cancer and lung metastases, failed since the patient died 8 months after surgery.     

Quantitative Progesterone Receptor Expression and Efficacy of Anti‐estrogen Therapy in Breast Cancer

The central role of estrogen receptor (ER) presence in predicting which breast cancer patients are likely to benefit from anti‐estrogen therapies is well‐established, but the added benefit of progesterone receptor (PR) and in particular low levels of PR is less well understood. The objective of this study was to determine the quantitative relationship between borderline levels of PR and subsequent benefit from anti‐estrogen therapy. We examined data from 447 patients, age 50 or older. ER and PR levels were quantitated by conventional ligand binding assay and Scatchard plot analysis or by enzyme‐linked immunoassay. Comparison of clinical outcome in relation with ER and PR status was calculated using Kaplan‐Meier actuarial survival analysis and the log‐rank test. Subpopulation treatment effect pattern plot (STEPP) analysis was used to explore the interaction between treatment effects and ER or PR levels for the 409 patients with ER values greater than 0. For anti‐estrogen treated patients, when the ER and PR positivity cut‐off was set at 1.0 fmole/mg protein, there was a statistically significant advantage for patients with ER+PR+ over ER+ PR? tumors for both breast cancer‐free interval (BCFI) and overall survival (OS). STEPP analysis found no overall interaction between treatment outcome (5 year survival probability) and levels of hormone receptor. However, patients with borderline PR levels did not appear to benefit from anti‐estrogen therapy. PR levels above borderline in addition to the presence of ER predicts an increased probability of benefit from anti‐estrogen therapy in breast cancer patients.     

Prognostic and predictive value of TFF1 for adjuvant endocrine therapy in Chinese women with early ER positive breast cancer: Comparing aromatase inhibitors with tamoxifen

Factors that predict in favor of an aromatase inhibitors (AIs) over tamoxifen (TAM) in estrogen receptor (ER) breast cancer remains to be identified. We compared progesterone receptor (PR) and trefoil factor 1 (TTF1) status (+ve versus −ve) as predictive of superior effect of AI’s over tamoxifen among a total of 1973 Chinese women with early ER+ breast cancer. The expression of TFF1 was independently associated with ER and PR. However, there was no correlation with TFF1 and HER-2 expression. Treatment effect was more pronounced in the ER+/TFF1+ postmenopausal patients with a hazard ratio favoring AIs (HR = 0.397, 95%CI 0.183-0.860), but not in the PR positive cohorts (HR = 0.466, 95%CI 0.186-1.164). We suggested that AIs was better than TAM especially in the postmenopausal patients with ER+/TFF1+ breast cancer; however the clinical application of this observation still requires further prospective studies.     

ER和PR及HER-2表达与乳腺癌分子分型及临床特征和预后的关系

目的:利用雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体2(HER-2)的免疫组织化学检测结果将乳腺癌简易分为4种分子亚型,并探讨这4种分子亚型的临床特征和影响预后的相关因素。方法:根据ER、PR及HER-2的免疫组织化学检测结果,采用回顾性方法将本院收治的175例乳腺癌患者简易分为类luminal A型、类luminal B型、类HER-2(+)型及类basal-like型4种类型。对各型的临床特征采用SPSS17.0统计软件进行分析,并用Kaplan-Meier法和Cox回归分析各型乳腺癌患者的生存情况及预后因素。结果:在175例乳腺癌患者中,类luminal A型、类luminal B型、类HER-2(+)型及类basal-like型分别占56.00%(98/175)、17.71%(31/175)、12.57%(22/175)和13.71%(24/175)。类basal-like型与类luminal A型相比,患者无瘤生存率较低(P0.05)。经Cox多因素预后分析,淋巴结阳性患者的预后较淋巴结阴性患者差;类luminal A型患者预后最好,而类basal-like型患者预后最差。结论:淋巴结状况及分子分型是影响乳腺癌预后的重要因素。依据ER、PR及HER-2行乳腺癌分子分型与国际公认分型的临床表现及预后基本一致,对指导基层医院的乳腺癌预后及治疗同样具有重要意义。     

雌激素诱导蛋白及其影响因素在乳腺癌组织中的表达与临床意义

目的：探讨雌激素诱导蛋白（PS2）在乳腺癌中的表达及与其影响因素的关系.方法：应用免疫组织化学SP法检测PS2及其影响因素、ER、PR、c-erbB2在52例乳腺癌中的表达.结果：PS2在乳腺癌中的表达率为59.6%（31/52）.PS2阳性表达与月经状况、ER、PR相关,与肿瘤大小、临床分期、淋巴结状况无关;PS2阳性表达者较阴性表达者5年生存率高,复发率低.结论：PS2可作为预测乳腺癌患者预后的一个独立因子,对乳腺癌患者的抗雌激素治疗有一定指导意义.     

Nutritional factors,physical activity,and breast cancer by hormonal receptor status

PurposeTo investigate the association between food and nutrient intake, occupational and leisure-time physical activity, and body mass index and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status.MethodsWe analyzed data from a hospital-based case–control study conducted between 1991 and 1994 in Italy, including 1075 women with incident breast cancer and 1477 controls.ResultsThe associations with breast cancer risk were similar according to ER status for all risk factors considered. In particular, significant reduced risk of ER? and ER+ breast cancers were observed for raw vegetables (multivariate odds ratio, OR, for high vs low consumption: 0.6 and 0.7, respectively) and for polyunsaturated fats (OR: 0.6 and 0.7, respectively). No significant heterogeneous risk estimates were observed for combinations of ER and PR status.ConclusionsOur study does not suggest major differences risk for various dietary and lifestyle factors according to ER and PR breast cancer subtypes.     

Roles of hormone replacement therapy and iron in proliferation of breast epithelial cells with different estrogen and progesterone receptor status

Estrogen and iron play critical roles in a female body development and were investigated in the present study in relation to in vitro cell proliferation. Prempro, a hormone replacement therapy drug, and 17beta-estradiol (E2) were shown to increase cell proliferations in estrogen receptor positive (ER+) cells independent of progesterone receptor (PR) status. For example, increased cell proliferation was observed in ER+/PR+ human breast cancer MCF-7, its matching non-cancerous human breast epithelial MCF-12A, and ER+/PR+ murine mammary cancer MXT+ cells, but not in ER-/PR- MDA-MB-231, its matching non-cancerous MCF-10A, and MXT- (ER-/PR+) cells. By mimicking post-menopausal conditions of high estrogen in local breast tissue and increased iron levels due to cessation of menstrual periods, E2 and iron were shown to exert synergistic effects on proliferation of MCF-7 cells and significantly increased Ki67 and proliferating cell nuclear antigen. Western blotting of E2-treated ER+ but not ER- cells showed that E2 also increased transferrin receptor (TfR). Further studies are needed to assess the mitogenic effects of iron and estrogen in normal post-menopausal breast.     

BS10THE PROGNOSTIC SIGNIFICANCE OF THE OVEREXPRESSION OF THE GROWTH FACTOR CRIPTO IN PATIENTS WITH BREAST CANCER

Purpose To determine the prognostic significance and long term survival of breast cancer patients with overexpression of the epidermal growth factor Cripto. Methodology 120 formalin fixed paraffin embedded breast cancer specimens were constructed on a tissue microarray and detection of Cripto carried out by immunohistochemical staining. Patients were treated between 1989 and 1995 and the median follow up was 125 months. We examined the association of Cripto positivity with age, menopausal status, grade and size of tumour, lymph node status, tumour type, ER/PR/HER2 status, Ki67 and Nottingham Prognostic Index (NPI). Results 48% of patients were Cripto positive. We demonstrated a significant association between overexpression of Cripto and NPI (p < 0.01), grade of tumour (p < 0.01), progesterone receptor (p = 0.02), Ki 67 (p = 0.02), tumour type (p = 0.04) and most importantly overall survival (p = 0.0003). Cox regression analysis revealed Cripto to be an independent prognostic variable for survival – HR 2.79 (95% CI 1.20–6.50). Conclusion Overexpression of Cripto is associated with high grade poor prognostic breast cancer and a significantly decreased patient survival. Future research is required to confirm these findings and to develop an anti‐Cripto humanised antibody for clinical use.