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PubMed2026

Outcomes of elacestrant in patients with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer who received prior endocrine therapy and cyclin-dependent kinase inhibitor in a real-world setting.

BACKGROUND: Real-world data analyses show durable benefits with elacestrant, with or without prior treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). This cohort focused on patients with ER-positive/HER2-negative estrogen receptor 1 (ESR1)-mutated metastatic breast cancer (mBC) treated with elacestrant after at least one line of endocrine therapy (ET) combined with CDK4/6i (N = 281). PATIENTS AND METHODS: Claims data from the Komodo Research Dataset linked with Foundation Medicine clinical-genomics data were used. Primary outcome was median time-to-next-treatment (mTTNT). RESULTS: In patients with ER-positive/HER2-negative ESR1-mutated mBC who received one to two prior lines of ET + CDK4/6i (n = 108), mTTNT with elacestrant was 8.2 months [95% confidence interval (CI) 6.0-12.2]. In patients who received one to two prior lines of ET + CDK4/6i for ≥12 months (n = 85), mTTNT was 9.0 months (95% CI 7.7-13.7), including an mTTNT of 12.2 months (95% CI 9.0-not reached) in those who received one prior line of ET (n = 31). In patients with liver and/or lung metastasis (n = 169), mTTNT was 6.9 months (95% CI 5.8-8.3), whereas it was 7.4 months (95% CI 5.6-12.9) in patients with brain metastasis (n = 68). In patients with coexisting ESR1- and phosphoinositide 3-kinase-pathway-mutated tumors (n = 115), mTTNT was 6.1 months (95% CI 5.0-8.1). CONCLUSIONS: Elacestrant showed durable benefits in patients with ER-positive/HER2-negative ESR1-mutated mBC previously exposed to at least one line of ET + CDK4/6i, reinforcing the role of elacestrant as a potential first-choice option for patients with endocrine-sensitive tumors.

ESR1 mutation↗

PubMed2026

PGR expression as a pharmacogenomic companion biomarker to GENE70-derived genomic risk in ER-positive/HER2-negative breast cancer.

BACKGROUND: The biology of the estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancers is heterogeneous even when they are categorized by their risk via genomics. Transcriptomic PGR expression reflects endocrine pathway activity and may provide complementary biological information within established GENE70-derived genomic-risk categories. Whether this molecular marker improves the biological interpretation of genomic-risk stratification beyond conventional clinicopathological assessment remains uncertain. OBJECTIVES: The aim of this study was to determine whether transcriptomic PGR expression provides complementary biological and prognostic information within reconstructed GENE70-derived genomic-risk categories and refines the characterization of endocrine-related tumour biology in ER-positive/HER2-negative breast cancer. METHODS: This study analysed publicly available transcriptomic and clinical data from three cohorts: METABRIC (discovery cohort), GSE96058/SCAN-B cohort (validation cohort) and TCGA-BRCA cohort (molecular validation cohort). The GENE70-derived genomic-risk score was reconstructed for each cohort using matched genes. Cox regression, Kaplan-Meier analysis and subgroup comparisons were used to assess relationships between PGR expression, clinicopathologic variables, molecular features and survival outcomes. RESULTS: Across the three independent cohorts, low transcriptomic PGR expression was consistently associated with higher GENE70-derived genomic risk, increased MKI67 expression, reduced ESR1 expression and enrichment of the Luminal B subtype. Survival findings differed between cohorts. In the discovery METABRIC cohort, transcriptomic PGR expression showed heterogeneous associations with survival, particularly within GENE70-derived high-risk subgroups, whereas the external GSE96058/SCAN-B validation cohort demonstrated consistent associations between low PGR expression and poorer overall survival in both the overall ER-positive/HER2-negative population and GENE70-derived high-risk subgroups. CONCLUSION: These findings suggest that transcriptomic PGR provides complementary biological and prognostic information within GENE70-derived genomic-risk categories. However, because treatment response was not evaluated in the present study, the findings should not be interpreted as evidence of predictive or pharmacogenomic utility and prospective studies incorporating treatment-response analyses are required before such applications can be established.

Humans↗

PubMed1979

Correlation of estrogen receptor levels with histology and cytomorphology in human mammary cancer.

Histologic and cytomorphologic features of mammary carcinoma have been correlated with estrogen receptor (ER) levels determined by the dextran-coated charcoal (Scatchard) analysis in 51 primary mammary carcinomas. The results were expressed as follows: ER-positive above and ER-negative below 10 fmol/mg protein and ER-rich above and ER-poor below 250 fmol/g tissue for premenopausal patients (750 fmol for postmenopausal patients). Most lobular carcinomas were ER-positive and ER-rich (84.6%). A similarly high percentage (88.9%) of ER-positive and ER-rich determinations was seen in ductal carcinomas with tubular features, whereas only about half of the remaining ductal tumors were ER-positive or ER-rich. The highest ER values were obtained in the lobular carcinomas and in ductal carcinomas with tubular features. Three cytomorphologic indices independent of variation in tumor histology showed a strong correlation with ER values: maximal epithelial cellularity of the tumor (P less than 0.001); cellular size (P less than 0.05); nuclear size (P less than 0.05).

Adult↗

PubMed1977

Simultaneous presence of receptors for complement and sheep red blood cells on human fetal thymocytes.

The cells of four thymus glands, two at 12 weeks, one at 16 weeks and one at 22 weeks gestational age, were examined cytochemically for enzymic activity and for surface markers. The reactions for chloroacetate esterase, peroxidase, and alkaline phosphatase were negative and the reaction for nonspecific esterase was only weakly positive in some of the cells. In contrast, nearly all thymocytes at the 12th gestational week showed strong focal acid phosphatase (acP) activity. The number of acP-stainable cells and the staining intensity declined progressively. A high percentage of thymocytes in early fetal life express a complement receptor (CR); the proportion of CR-bearing cells decreased while cells forming rosettes with sheep erythrocytes (possessing erythrocyte receptors: ER) correspondingly increased during fetal life. Using a mixed rosette assay, up to 30% of the thymocytes at 12 weeks gestation were found to bear CR and ER simultaneously. The number of CR- and ER-positive cells also declined progressively with fetal age. These findings show that CR-positive, ER-negative thymus cells mature into CR-negative, ER-positive thymocytes via a CR-positive and ER-positive intermediate cell, indicating that mature ER-positive thymocytes do not originate from another cell line lacking CR. The changes in surface markers during early T cell maturation is relevant to certain lymphomas whose cells also show strong focal acP activity and also express both CR and ER. These lymphoma cells may correspond to fetal thymocytes or T precursor cells present in small numbers after birth.

Binding Sites↗

PubMed1976

Mechanisms responsible for defective human T-lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections.

The expression of selected lymphocyte surface-membrane markers was evaluated in 37 patients with acute viral hepatitis B, 10 of whom were studied serially through the resolving and convalescent phases of disease. Bone marrow-derived (B) lymphocytes were identified by reference to surface immunoglobulin, whereas normal thymus-derived (T) lymphocytes were assayed by their capacity to form spontaneous nonimmune rosettes with sheep erythrocytes (E rosettes, ER). During the acute and resolving phases of viral hepatitis B, the relative and absolute number of ER-positive lymphocytes was significantly reduced, whereas the number of surface immunoglobulin-positive lymphocytes and the absolute lymphocyte count remained normal. This resulted in the appearance of a third population of cells, deficient in respect to both surface immunoglobulin and ER markers. Such cells accounted for nearly 25% of peripheral blood lymphocytes, approximately 5 x 105ml blood. Depression of the number of ER-positive lymphocytes occurred at least once during the course of disease in every patient studied serially, and was observed in 55 of 67 individual assays of the 37 cases of acute viral hepatitis B. Lymphocytes from some patients reacquired ER function when cultured in fetal calf serum but not in the presence of autologous serum. Such autologous serum was capable of suppressing ER function of lymphocytes from normal donors. The extrinsic suppression of er function by a serum factor (designated as the Rosette Inhibitory Factor), was found to be time dependent, characterized by a 4-h latent period and requiring approximately 18 h for maximum attenuation of ER function. The Serum Rosette Inhibitory Factor was: (a) heat and freeze-thaw stable, (b) nondialyzable, (c) physically separable from hepatitis B surface antigen, (d) not a lymphocytotoxic antibody, and (e) had the buoyant density of a lipoprotein. This extrinsic mechanism was observed in 41.8% of patients with reduced numbers of ER-positive lymphocytes. The Rosette Inhibitory Factor was not detectable in the serum of the remaining 58.2% of the cases of acute and resolving viral hepatitis B despite the presence of reduced numbers of ER-positive lymphocytes. The lymphocytes from these cases did not reacquire ER function when cultured in the absence of autologous serum. The mechanisms responsible for the suppression of normal ER function in these cases appears to be intrinsic to the lymphocytes and not the result of a humoral factor. The T lymphocyte lineage of cells deficient in respect to ER function, whether of intrinsic or extrinsic type, was demonstrated by their capacity to form spontaneous rosettes with neuraminidase-treated sheep erythrocytes. Both intrinsic and extrinsic suppression of T lymphocyte ER function commonly occurred during the first 4 wk of acute viral hepatitis B.9 of the 10 patients followed serially continued to manifest defective ER function at 12 wk...

Adult↗

PubMed1978

Sex hormone-binding globulin and estrogen receptor in breast cancer: technique and preliminary clinical results.

The binding capacities of SHBG (sex hormone-binding globulin) and ER (estrogen receptor) were measured by agar gel electrophoresis with dextran-coated charcoal treatment and also by sucrose density gradient ultracentrifugation in the sera from 19 women with breast cancer to assay the correlation between SHBG and ER in breast cancer. SHBG levels were also measured by agar gel electrophoresis with dextran-coated charcoal treatment in control sera from 20 normal women. Two kinds of 17 beta-estradiol-binding substances were recognized in the cytosol of breast cancer cells and they were confirmed to be ER and SHBG. Out of 13 postmenopausal patients with breast cancer, the SHBG levels in 6 ER-positive cases (66 +/- 13 pmol/ml plasma, mean +/- SD) were significantly higher than the levels of 10 controls (35 +/- 7.6 pmol/ml; P less than 0.005). SHBG levels in 7 ER-negative patients (34 +/- 7.9 pmol/ml plasma) did not significantly differ from the levels of the controls, but differed significantly from the levels of ER-positive patients (P less than 0.005). Out of 6 premenopausal breast cancer patients, the SHBG levels in 5 ER-positive cases (63 +/- 7.5 pmol/ml plasma) tended to be higher than the levels in 10 controls (55 +/- 4.7 pmol/ml plasma), but did not achieve statistical significance (P greater than 0.05). The findings suggest that correlation between SHBG and ER in postmenopausal breast cancer is possible, but no significant difference was noted between the SHBG levels in ER-positive premenopausal breast cancer patients and premenopausal normal women.

Adult↗

PubMed1979

Significance of estrogen receptor assay in cytotoxic chemotherapy in relation to previous endocrine therapy of advanced breast cancer patients.

In 36 patients with advanced breast cancer, most of whom had been subjected to major endocrine ablation therapy such as bilateral adrenalectomy, correlation between the presence or absence of estrogen receptor (ER) in tumors and response to chemotherapy was investigated. Complete or partial response was obtained in 6 of 14 (42.6%) patients with ER-positive tumors and in 3 of 22 (13.6%) patients with ER-negative tumors (P = 0.1). The response to chemotherapy was not influenced by the concentration of ER in tumors. Distribution of the duration of regression readings and the survival time was not significantly different between the patients with ER-positive and -negative tumors. Some regimens which did not include adriamycin, such as MFC (mitomycin-C, 5-fluorouracil, and cytosine arabinoside) had a good effect on the ER-positive cases, whereas the response to regimens including adriamycin was not influenced by the ER positiveness of the tumors. In the classification of some clinical parameters of the patients, response of the patients with ER-negative tumors does not seem to be better than that of the patients with ER-positive tumors. Responses to the major endocrine ablation therapy and also to the subsequently carried out chemotherapy were influenced by the presence or absence of ER in tumors before the endocrine therapy.

Adrenalectomy↗

PubMed2026

Estrogen Receptor, GATA-3, TTF-1, and KRAS in Endometrial Carcinoma of No Specific Molecular Profile: Prognostic or Diagnostic Markers?

Endometrial carcinoma with no specific molecular profile (NSMP) is a clinicopathologically heterogeneous group of diseases with an overall intermediate prognosis. Prognostic refinement is needed for better personalized treatment. The updated European Society of Gynecological Oncology-European Society for Radiotherapy and Oncology-European Society of Pathology guidelines for endometrial carcinoma stratify NSMP according to histotype and estrogen receptor (ER) status. ER (with other ancillary markers) also helps differentiate histotypes of endometrial carcinoma. This study describes clinicopathological characteristics of ER-positive and -negative-NSMP endometrial carcinoma. Furthermore, we investigate the prognostic and diagnostic significance of ER, GATA3, TTF1, and KRAS in a large and relatively unselected NSMP carcinoma cohort. POLE sequencing results and immunohistochemistry for p53, mismatch repair proteins, and ER were available for 930 samples of endometrial carcinoma. Within NSMP cases (n = 377), 22 samples presented ER staining in <1% of the carcinoma cells, 5 cases in 1% to 9%, and 350 cases in ≥10%. ER expression ≥10% predicted an excellent outcome (comparable with POLE-mutated cases) in univariable analysis, where ER negativity (<10%) was associated with a poor outcome (comparable with p53 abnormal cases). Most ER-positive NSMP cases were low-grade endometrioid carcinomas, whereas most ER-negative NSMP cases were nonendometrioid or high-grade endometrioid carcinomas. In addition to high-risk histotype, ER negativity was associated with various other clinicopathological risk factors. In multivariable analysis adjusting for histotype and other risk factors, ER did not independently predict disease progression (P = .814). No disease-related deaths were observed in the rare (n = 3) patients with ER-negative-low-grade endometrioid carcinoma. GATA3/TTF1 positivity and KRAS mutation were discovered not only in mesonephric-like carcinoma but also in endometrioid carcinoma. No prognostic relevance was found for these markers. In conclusion, the different prognosis of ER-positive vs ER-negative-NSMP endometrial carcinoma is not attributable to ER status itself but rather to its strong correlation with histotype and other clinicopathological risk factors. Limited specificity of GATA3, TTF1, and KRAS warrants caution in their use as diagnostic markers of mesonephric-like carcinoma.

Humans↗

PubMed1976

The surgical implications of estrophile protein estimations in carcinoma of the breast.

Assays of estrophile protein (ER) in 161 patients with no previous additive or ablative hormonal therapy have been analyzed; 47.2 percent were ER positive; 52.8 percent ER negative. A total of 37.5 percent of premenopausal and 50.8 percent of postmenopausal patients had ER-positive tumors. The effects of additive and ablaive hormonal therapy were observed in 75 patients; 63.5 percent of the ER-positive group and 8.6 percent of the ER-negative group responded, but the incidence in the ER-negative group is thought to be spuriously high. The level of the ER content in the ER-positive group did not influence the degree of response. The ER-negative group had a shorter life span after discovery of the tumor and was more likely to develop dominant visceral metastases. Of 15 patients followed with sequential ER assays after hormonal therapy (additive and/or ablative), 14 demonstrated substantial falls in ER levels but these did not correlate with the clinical response. Tumor assayed in nine patients after irradiation of the lesion contained no demonstrable ER. ER assays of breast cancer tissue proved to be a useful but imperfect tool in predicting clinical progress following hormonal maneuvers but some readings may be spuriously low due to imperfect techniques of measurement, prior exogenous hormonal administration or hormonal ablation, and previous irradiation of the tumor.

Adrenalectomy↗

PubMed1978

Steroid receptors study in breast carcinoma.

Estrogen receptors (ER) were measured on specimens taken from 27 patients with benign breast conditions and 109 patients with breast cancer. Using sucrose gradient assay, 15% (4/27) of benign lesions and 56% (61/109) of malignant tumors were estrogen receptor-positive (ER-positive means 8S or 8S+4S levels more than 7 fmoles/mg cytosol protein). Progesterone receptors (PR) were tested on specimens from 28 patients and 39% (10/26) of the cancers were PR-positive. ER protein activity was not correlated with stage, histology, size of primary lesions, or extent of axillary or distant metastasis. Tumors with low ER levels are more likely to recur, and recurrent tumors after longer disease-free intervals are more likely to be ER-positive. Detailed analysis showed that ER levels did correlate with age and serum albumin levels. Concentrations of serum alpha1-globulin were decreased, while IgG and IgM were significantly increased among patients with positive ERs. Eighteen evaluable patients with advanced breast cancer had endocrine therapy, 13 had objective response. Twelve of these 13 had 8S receptor above 10 fmoles/mg, or 4S above 15 moles/mg, or 8S+4S above 25 fmoles/mg. The one exceptional patient had tumor with high PR but without detectable ER.

Adult↗

PubMed2026

Identification of genomic features that uniquely impact estrogen receptor alpha binding and its effects on gene expression in endometrial cancer.

Estrogen receptor 1 (ESR1, also known as estrogen receptor alpha or ER) is an established oncogenic transcription factor in breast and endometrial cancer; however, more is known about the mechanisms controlling ER behavior in breast cancer, and therapies targeting ER have been much more successful in breast cancer. To address this disparity, we characterize the genomic features that control ER in endometrial cancer and determine to what extent these factors differ from those in breast cancer. We focus on the locations of estrogen response elements (EREs), ER's preferred DNA-binding motif, throughout the human genome. To identify factors that predict ER genomic binding and effects on target gene expression, we apply machine learning to genomic data for each ERE in Ishikawa cells (ER-positive endometrial cancer) and T-47D cells (ER-positive breast cancer). Many of these factors, such as chromatin accessibility and histone modifications, are predictive of ER activity in both cell lines. However, the transcription factors that predict ER activity are cell type specific, including FOXA1 and GATA3 in T-47D cells and ETV4 and SOX17 in Ishikawa cells. In addition, the features that predict ER binding and effects on gene expression differ, with transcription at EREs in the absence of estrogen being predictive of ER regulatory activity. A CRISPR knockout screen in Ishikawa cells, as well as follow-up experiments, confirms the discovery that SOX17 controls ER activity in endometrial cancer cells. These results identify important genomic features of ER binding and regulatory activity and how these features differ between endometrial cancer and breast cancer cells.

Humans↗

PubMed2025

Mapping the FOXA1 Interactome in ER+ Breast Cancer Cells Using Proximity Labeling Reveals Novel Interactions with the Orphan Nuclear Receptor NR2C2.

UNLABELLED: FOXA1 is a pioneer transcription factor essential for chromatin accessibility and transcriptional regulation in hormone-driven cancers. In breast cancer, FOXA1 plays a central role in facilitating nuclear receptor binding, reprogramming enhancer landscapes, and promoting transcriptional changes associated with therapy resistance. Whereas FOXA1's function has been primarily studied in the context of estrogen receptor-α (ER), its broader protein interaction network remains incompletely defined. In this study, we systematically map FOXA1-interacting proteins in ER-positive breast cancer cells using proximity-dependent biotin labeling (miniTurbo) combined with quantitative LC-MS/MS proteomics. We engineered MCF-7 cell lines stably expressing miniTurbo-tagged FOXA1 at either the N-terminus or C-terminus to ensure comprehensive coverage of interaction interfaces. This approach recovered known FOXA1 partners, including AR, MLL3, YAP1, and GATA3, and identified 157 previously unreported FOXA1 interactors. Notably, 42 of these novel partners, including NR2C2, were significantly associated with poor relapse-free survival in patients with ER-positive breast cancer. To demonstrate the utility of this resource, we characterized the FOXA1-NR2C2 interaction in depth. Integrating chromatin immunoprecipitation sequencing and RNA sequencing, we show that FOXA1 and NR2C2 co-occupy a subset of genomic regions and drive co-regulated transcriptional programs involved in tumor progression. Our study reveals an expanded FOXA1 interactome and new insights into its functional network in breast cancer, providing candidate proteins for further exploration as biomarkers or therapeutic targets. IMPLICATIONS: These findings expand the FOXA1 interactome in breast cancer and uncover new candidate proteins with potential as biomarkers and therapeutic targets in hormone-driven tumors.

Humans↗

PubMed2026

Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.

Carriers of germline BRCA1/2 pathogenic variants (gBRCA1/2 PVs) have elevated young-onset breast cancer risk. To define the pretreatment genomic landscapes of young-onset gBRCA-associated breast cancer, we evaluated 136 treatment-naive tumors diagnosed before age 50 in the prospective POSH study and 66 noncarriers from The Cancer Genome Atlas. Using whole-exome sequencing, we analyzed somatic variation, allele-specific loss of heterozygosity (asLOH), homologous recombination deficiency (HRD), and single-base substitution (SBS) signatures. gBRCA1 and gBRCA2 breast cancers had high rates of asLOH but differed significantly in average HRD scores and median SBS composition of signatures SBS1 (aging-associated), SBS18 (ROS-associated), and SBS3 (HRD-associated). Compared with gBRCA2 tumors, gBRCA1 tumors with asLOH were significantly enriched for alterations in hallmark ROS, DNA repair, and epithelial-mesenchymal transition pathways. In ER-positive, HER2-negative tumors from gBRCA1/2 carriers compared with noncarriers, we found significant enrichment of RB1, TP53, FAT1, and MYC single-nucleotide variants, indels, and copy number variants associated with CDK4/6 inhibitor (CDK4/6i) resistance. Together, these findings demonstrate significant differences between gBRCA1- and gBRCA2-associated breast cancers, and preexisting CDK4/6i resistance mechanisms, supporting prospective trials comparing individualized therapy for gBRCA1 versus gBRCA2 carriers and comparing poly(ADP-ribose) polymerase inhibitors versus CDK4/6i for ER-positive gBRCA1/2-associated breast cancer.

Humans↗

PubMed2026

Multigene testing to guide clinical adjuvant decisions in breast cancer: An overview focused on the assessment of the quality of evidence with the grading of recommendations assessment, development and evaluation (GRADE) approach.

Multigene tests have emerged as valuable tools in guiding adjuvant chemotherapy decisions for patients with ER-positive/HER2-negative early breast cancer. This study applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence supporting the clinical utility of these tests. We focused on OncotypeDX® and MammaPrint®, the two tests evaluated in prospective randomized trials. The analysis was structured around the clinical question of whether these tests should be recommended for patients with ER-positive, HER2-negative, lymph node-negative or up to 3 lymph nodes-positive invasive breast cancer to guide adjuvant chemotherapy decisions. Our findings reveal that OncotypeDX® demonstrates high clinical utility in sparing chemotherapy for older/postmenopausal patients, with convincing quality of evidence for both node-negative and node-positive patients. The clinical utility of MammaPrint® appears more controversial, with conflicting results between node-negative and node-positive patients. A particularly critical aspect remains the clinical usefulness of these tests in younger/premenopausal women, where the benefit of adjuvant chemotherapy was shown but with potential biases in the study designs. Despite the established role of multigene tests and their availability in Italy since 2021, their uptake in clinical practice remains suboptimal. This formal appraisal of the clinical utility of genomic tests, particularly OncotypeDX®, aims to reinforce their fundamental role in personalizing adjuvant treatment decisions and optimizing resource allocation. The study underscores the importance of these tests in sparing unnecessary chemotherapy toxicities and costs, while emphasizing the need for further research to address remaining uncertainties, especially in younger patient populations.

Humans↗

PubMed1977

Estrogen receptor and endocrine responsiveness in Japanese versus American breast cancer patients.

We have compared the incidence of estrogen receptor (ER) in breast tumors and its clinical correlation with responses to endocrine therapies in Japanese and American patients. There was no correlation between tumor histopathology and the presence of ER, and the ER values in primary and metastatic lesions from the same patients were similar in most Papanese cases. Japanese patients with low and high plasma estradiol levels had identical incidences of ER-positive tumors. The correlation between tumor ER and response to endocrine therapy is similar between Japanese and American patients. The incidence of ER-positive tumors is higher in postmenopausal American patients in both primary and metastatic lesions. It is possible that the reported increase in tumor lymphocyte infiltration in Japanese patients may explain this difference. The reported 5-year survival advantage of Japanese breast cancer patients cannot be explained by differences between the two populations in the response to endocrine therapy for advanced disease.

ABO Blood-Group System↗

PubMed2026

Effects of short-course preoperative endocrine therapy on tumour morphology and immunohistochemical profile in oestrogen receptor-positive, HER2-negative breast cancer.

AIMS: Short-term preoperative endocrine therapy (ET) is increasingly used in oestrogen receptor (ER)-positive, HER2-negative breast cancer as a functional test of endocrine sensitivity. We aimed to characterise histomorphological and immunophenotypic changes following preoperative ET and to identify predictors of endocrine response, defined as post-treatment Ki67 ≤ 10%. METHODS AND RESULTS: In this retrospective single-centre study, 180 patients treated with short-course preoperative ET (median duration 29 days) were compared with 151 patients undergoing primary surgery without ET. Paired biopsy and resection specimens were assessed for histological features, stromal proportion, stromal tumour-infiltrating lymphocytes (strTILs) and expression of ER, progesterone receptor (PR), HER2 and Ki67. Genomic risk was determined using the MammaPrint assay. Preoperative ET was associated with a significant reduction in tumour proliferation, with 73.9% of cases showing post-treatment Ki67 ≤ 10% compared with none in controls (P < 0.001). Histological grade decreased in 36.7% of ET-treated tumours versus 7.9% of controls (P < 0.001), predominantly reflecting reduced mitotic activity. ER expression remained stable, whereas PR expression decreased more frequently following ET (P < 0.001) and was independently associated with Ki67-defined response. HER2-low status was more frequently observed after ET (P < 0.001), but HER2 expression and microenvironmental parameters, including strTILs, were not associated with response. High genomic risk was independently associated with a lower likelihood of achieving post-treatment Ki67 ≤ 10% (P < 0.001). CONCLUSIONS: Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.

Humans↗

PubMed1978

Some comments on the necessity of receptor determination in human breast cancer.

Estrogen receptors (ER's) were determined by agar gel electrophoresis in 105 human mammary tumor biopsies. Fifty-three tumor specimens revealed measurable amounts of receptor, and 64% of these patients showed an objective remission after endocrine treatment. If we also include cases with partial remission, previous response, and arrested growth but no actual remission, the benefit rate increases to 87%. The corresponding percentage in the ER-negative groups is 13%. In a retrospective study of 42 patients with human breast cancer, a correlation between ER finding and remission rate after chemotherapy was found. Of the ER-negative patients, 71% showed an objective remission after polychemotherapy, whereas only 43% of the ER-positive cases revealed such remission. The presented data are discussed with special regard to their clinical relevance.

Antineoplastic Agents↗

PubMed2026

The 21-gene recurrence score assay as a tool for predicting recurrence risk and guiding adjuvant treatment selection in early breast cancer.

INTRODUCTION: Estrogen receptor-positive (ER+), HER2-negative breast cancer is the most common breast cancer subtype. While adjuvant endocrine therapy reduces recurrence risk, identifying which patients benefit from the addition of chemotherapy remains a key clinical challenge. The Oncotype DX® 21-gene Recurrence Score assay (Exact Sciences, via Genomic Health, Inc.) was developed to address this by quantifying distant recurrence risk and informing chemotherapy decisions in early-stage ER+/HER2- disease. AREAS COVERED: This diagnostic profile reviews the development, validation, and clinical evidence for Oncotype DX, including findings from the TAILORx and RxPONDER prospective trials and the subsequent development of hybrid tools integrating genomic and clinicopathological data. Alternative multiparameter molecular tests (MammaPrint, Prosigna, EndoPredict, Breast Cancer Index) are summarized and compared. We review international guideline recommendations, decision impact studies, cost-effectiveness evidence, and ongoing trials. EXPERT OPINION: Oncotype DX has strong prognostic evidence and has meaningfully reduced chemotherapy use, though its case as a biomarker predictive of therapeutic effect from chemotherapy rests on trial designs with important limitations. Its independent prognostic contribution beyond comprehensive clinicopathological assessment requires further clarification, and cost-effectiveness varies substantially by indication and healthcare setting.

Humans↗