Progesterone Receptor Positive Status Research Articles

An initial experience of robot-assisted breast conserving surgery: A multicenter study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).

543 Background: Robot-assisted breast conserving surgery (RABCS) have cosmetic benefit without any scar on the breast over conventional breast conserving surgery (CBCS). However, data on the feasibility and safety of the RABCS are limited. The aim of this study was to present the results of early experience of RABCS. Methods: A multi-center retrospective review was conducted to identify women who underwent RABCS as part of the Korea Robot-Endoscopy & Minimal Access Breast Surgery Study Group (KoREa-BSG) between August 2019 and October 2023. Information of the clinicopathologic characteristics, perioperative complications, operation time, recurrence, and re-operation were collected. Results: A total of150 patients underwent the RABCS procedure conducted by 10 breast surgeons at seven institutions. Invasive breast cancer was noted in 121 cases and ductal carcinoma in-situ was detected in 29 cases. Further, 75.3% and 65.3% of the patients had an estrogen and progesterone receptor positive status, respectively. A total of 35.3% of the patients had a HER2-positive status. In terms of the surgical technique, the Da Vinci SP system was more frequently used (60%). Gas insufflation was applied in 97.33% of the cases, and s entinel lymph node biopsy (SLNB) only was the most common axillary surgery (89.3%). The median duration of postoperative days was 5.4 days (range, 1.0-15.0 days). The incision location was the mid-axillary line and the median incision length was 37.1 mm (range, 27.0-60.0 mm). The median total operation time was 133.8 minutes (range, 62.0-295.0 minutes). 11 cases (7.3%) showed frozen margin positive, however only one case (0.7%) required re-operation because of permanent margin positive. Six patients (4%) developed surgical complications. Postoperative bleeding was found in one case and skin burn was found in five cases (3.3%); two cases (1.3%) required skin excision and three cases (2.0%) showed spontaneous resolution. There were no cases of conversion to open surgery or mortality. Only one case (0.7%) had recurrence. Conclusions: This was the first multicenter report of RABCS in the world. RABCS could be a technically feasible and safe. Further subsequent comparative study with CBCS and prospective research are needed to evaluate the surgical and oncologic outcomes.

Use of endocrine therapy for estrogen receptor-positive breast cancer among American Indians and Alaska natives.

American Indian/Alaska Native (AI/AN) women with estrogen receptor-positive (ER +) breast cancer have higher mortality compared to non-Hispanic whites (NHW). The purpose of this study is to compare rates of initiation of endocrine therapy (ET) between AI/AN and NHW and further determine survival outcomes for ER + breast cancer. We used the National Cancer Database to identify patients diagnosed with ER + breast cancer, stage I-III, between 2004 and 2017. Multivariable logistic regression was performed to determine factors associated with initiation of adjuvant ET. Overall survival was estimated using the Kaplan-Meier analysis and Cox proportional hazards modeling. We identified a total of 771,619 patients (AI/AN, n = 2473; NHW, n = 769,146). Compared to NHW, AI/AN patients were more likely to live in rural areas, be younger, and have tumors that were higher grade, node positive, and larger. Initiation of adjuvant ET was high in both groups and not significantly different between AI/AN and NHW. Independent predictors of ET initiation included rural location, age, higher tumor grade, node-positive disease, larger tumor size, and progesterone receptor-positive status. Initiation of ET was significantly associated with improved overall survival among all patients. Overall survival was significantly worse among the AI/AN population. AI/AN race was significantly and independently associated with worse overall survival after diagnosis of ER + breast cancer. We did not find a significant difference in the initiation of adjuvant ET between AI/AN and NHW. Exact reasons why AI/AN women with ER + breast cancer have higher mortality rates remain elusive but are probably multifactorial.

Association of Breast Tumour Expression of Cannabinoid Receptors CBR1 and CBR2 with Prognostic Factors and Survival in Breast Cancer Patients.

Cannabinoid receptors (CBR) are potential therapeutic targets for breast cancer. However, the role of CBR in breast cancer survival remains poorly understood. Data from a prospective cohort of 522 women diagnosed with invasive breast cancer between 2010 and 2012 were analysed. Clinical and pathological features were retrieved from electronic medical records. CBR expression was measured by immunohistochemistry. Adjusted partial Spearman correlations and multivariate Cox models were used to estimate associations with breast cancer prognostic factors and survival, respectively. The median follow-up was 92.0 months (range 7.0–114.0). CBR expression was heterogenous in tumours. Cytoplasmic expression of CBR1 was positively correlated with lymph node invasion (rs = 0.110; p = 0.0155) and positive status of the human epidermal growth factor receptor 2 (HER2) (rs = 0.168; p = 0.0002), while nuclear CBR2 was negatively correlated with grade (rs = −0.171; p = 0.0002) and positively correlated with oestrogen receptor and progesterone receptor-positive status (rs = 0.173; p = 0.0002 and rs = 0.121; p = 0.0084, respectively). High cytoplasmic expression of CBR2 was associated, with 13% higher locoregional and distant recurrences (HR = 1.13 [0.97–1.33]), though this association did not reach statistical significance. Although the few events occurring during follow-up may have limited the detection of significant associations, these results indicate that CBR expression in breast cancer deserves further investigation.

Changes of immunohistochemical biomarkers before and after neoadjuvant chemotherapy in breast cancer and their prognosis

Objective: To investigate changes in the expression of immunohistochemical (IHC) markers and factors associated with the effect of chemotherapy before and after neoadjuvant chemotherapy (NAC). Methods: A retrospective study included 200 breast cancer patients treated with NAC between January 2016 and December 2018. We analyzed the changes in the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 in pre- and post-treated samples and the predictive factors of NAC. Results: Among the 200 cases, 16 cases were luminal A, 108 cases were luminal B, 36 cases were HER2+subtype, and 40 cases were basal-like. Twenty-five patients (12.50%) achieved pathological complete remission (PCR).There were significant differences in PR and Ki-67 before and after NAC but there were no differences in ER and HER2.In univariate analysis, factors associated with PCR were tumor less than 5 cm(P=0.009), non-luminal breast cancer (P=0.001), ER negative(P=0.001), PR negative (P=0.029) and HER2 positive(P=0.001). Tumor less than 5 cm [P=0.020, OR=2.581, 95%CI (1.207, 5.753)], ER negative [P=0.011, OR=2.264, 95%CI (1.207, 4.248)] and HER2 positive[P=0.007, OR=2.412, 95%CI (1.275, 4.561)] remained predictive variables in multivariate analysis after correction for the other variables. Conclusions: The expression of Ki-67 decreases after NAC. Negative PR and ER and positive HER2 status are related to the efficacy of pCR for breast cancer, and have guiding significance for the prognosis evaluation of NAC.

NCAPG upregulation mediated by four microRNAs combined with activation of the p53 signaling pathway is a predictor of poor prognosis in patients with breast cancer.

The role of non-SMC condensin I complex subunit G (NCAPG) in breast cancer remains unclear. The present study used online databases, reverse transcription-quantitative PCR, flow cytometry and western blotting to determine the expression levels, prognosis and potential molecular mechanisms underlying the role of NCAPG in breast cancer. The association between NCAPG expression and several different clinicopathological parameters in patients with breast cancer was determined, and the results revealed that NCAPG expression was negatively associated with estrogen receptor and progesterone receptor positive status, but was positively associated with HER2 positive status, Nottingham Prognostic Index score and Scarff-Bloom-Richardson grade status. Furthermore, upregulated expression levels of NCAPG resulted in a poor prognosis in patients with breast cancer. A total of 27 microRNAs (miRNAs/miRs) were predicted to target NCAPG, among which four miRNAs (miR-101-3p, miR-195-5p, miR-214-3p and miR-944) were predicted to most likely regulate NCAPG expression in breast cancer. A total of 261 co-expressed genes of NCAPG were identified, including cell division cyclin 25 homolog C (CDC25C), and pathway enrichment analysis indicated that these co-expressed genes were significantly enriched in the p53 signaling pathway. CDC25C expression was downregulated in breast cancer and was associated with a poor prognosis. These findings suggested that upregulated NCAPG expression may be a prognostic biomarker of breast cancer.

Tumor grade and progesterone receptor status predict 21-gene recurrence score in early stage invasive breast carcinoma.

The 21-gene recurrence score (RS) assay is increasingly utilized to predict the risk of recurrence in early stage estrogen receptor (ER)-positive breast cancer. We hypothesize that tumor grade and progesterone receptor (PR) status predict RS categorization. We identified women between the ages of 18 and 74years with stage I or II, ER-positive, invasive carcinoma of the breast from the Surveillance Epidemiology End-Results database from 2010 to 2013. Multivariable logistic regression was performed to determine factors associated with high-risk RS. We identified 42,530 patients that met inclusion criteria. Multivariable logistic regression demonstrated that grade I tumors [OR (odds ratio) 0.33, 95% CI (confidence interval) 0.31-0.37] and PR positive (PR+) status (OR 0.16, 95% CI 0.15-0.17) were significantly less likely to be associated with high-risk RS. Of patients with grade I PR+ tumors, 1% was in the high-risk group by the traditional cutoffs and 4% was in the high-risk group by the TAILORx cutoffs. The percentage of patients with high-risk RS remained low for grade I PR+ tumors regardless of age, race, tumor size, and lymph node status. We found that grade I PR+ tumors are associated a < 5% probability of having high-risk RS regardless of other patient demographic or pathologic factors. This suggests that the histologic factors of grade and PR status should be taken into consideration before ordering the 21-gene recurrence score assay.

Association of CYP19 polymorphisms with breast cancer risk: A case-control study.

Background:The CYP19 gene is located on chromosome 15 and it plays an important role in aromatization, which results in production of estrogen from androgens. The mutation in this gene can result in either increased or decreased aromatase activity.Materials and Methods:A case-control study was designed to compare 250 breast cancer cases with 250 age-matched healthy controls. The frequency distribution of CYP19 polymorphism was assessed by polymerase chain reaction confronting two pair primers (PCR-CTPP).Results:CYP19 polymorphism at codon 39 Trp/Arg (W39R) results in three genotypes TT, TC, and CC, but in the present study CC genotype was not found in breast cancer cases as well as in controls. The TT genotype was significantly elevated in disease (90.8%) as compared to controls (68.5%). The frequency of TC was found to be increased in premenopausal women with breast cancer (12.2%) and the frequency of TT genotype was increased in patients who were postmenopausal (94.1%). The increased frequency of heterozygotes was found in cases with familial incidences of cancer (10.8%), estrogen and progesterone receptor positive status, node positive status (9.8%), and occupied in agriculture (14.8%). Higher frequencies of both TT and TC genotype were increased in patients with high body mass index (BMI). The frequency of TT genotype was found to be increased in advanced stage of the disease.Conclusion:Hence, we conclude that W39 with increased aromatase activity confers greater risk to develop breast cancer especially in postmenopausal women and might also contribute to advanced stage.

Multiparameter DNA content analysis identifies distinct groups in primary breast cancer

Background:Multiparameter flow cytometry is a robust and reliable method for determining tumour DNA content applicable to formalin-fixed paraffin-embedded (FFPE) tissue. This study examined the clinical and pathological associations of DNA content in primary breast cancer using an improved multiparametric technique.Methods:The FFPE tissue from 201 primary breast cancers was examined and the cancers categorised according to their DNA content using multiparametric flow cytometry incorporating differential labelling of stromal and tumour cell populations. Mathematical modelling software (ModFit 3.2.1) was used to calculate the DNA index (DI) and percentage S-phase fraction (SPF%) for each tumour. Independent associations with clinical and pathological parameters were sought using backward stepwise Binary Logistic Regression (BLR) and Cox's Regression (CR) analysis.Results:Tumours were grouped into four categories based on the DI of the tumour cell population. Low DI tumours (DI=0.76–1.14) associated with progesterone receptor-positive status (P=0.012, BLR), intermediate DI (DI=1.18–1.79) associated with p53 mutant tumours (P=0.001, BLR), high DI (DI⩾1.80) tumours with human epidermal growth factor receptor 2 (HER2)-positive status (P=0.004, BLR) and ‘multiploid tumours' (two or more tumour DNA peaks) did not show any significant associations. Tumours with high SPF% (⩾10%) independently associated with poor overall survival (P=0.027, CR).Conclusion:Multiparametric flow analysis of FFPE tissue can accurately assess tumour DNA content. Tumour sub-populations associated with biomarkers of prognosis or likely response to therapy. The alterations in DNA content present the potential for greater understanding of the mechanisms underlying clinically significant biomarker changes in primary breast cancer.

Estrogen levels act as a rheostat on p53 levels and modulate p53-dependent responses in breast cancer cell lines

A large proportion of breast cancers expresses the estrogen receptor alpha (ERα) and are dependent on estrogens for their proliferation and survival. The tumor suppressor TP53 encodes the p53 protein, an important mediator of the anti-proliferative and apoptotic effects of several treatments used for breast cancer. A significant proportions of breast tumors (20-30%) carry mutations in TP53 gene and these mutations are associated with poor survival and poor response to several types of chemotherapeutic treatments. While there is mounting evidence for functional interactions between p53 and ERα pathways in breast and other tissues, the impact of these interactions on response to chemotherapy and anti-hormone treatments remain largely unknown. Here, using estrogen-dependent breast cancer cell lines with different p53 status, we show that estrogens, through ERα, influence p53 protein levels and activities. Estrogen deprivation reduced, while estradiol increased p53 levels, in a time and dose-dependent manner. Both wild-type and endogenously expressed mutant p53 proteins were affected. This reduction in p53 protein levels resulted in reduced p53-dependent responses induced by DNA damage in p53 wild-type cells, lowering the capacity of doxorubicine to induce apoptosis. The p53 response appeared to be quantitatively but not qualitatively affected. These results suggest that ERα activity is required for a strong p53 response in estrogen-dependent breast cancer cells. These results are in line with previous observations that we made in a clinical series, where a larger effect of TP53 mutation status was found for patient survival in cases with progesterone receptor positive status, a marker of a functional ERα pathway. It would thus be important to further characterize the influence of ERα pathway on the predictive value of TP53 mutation status in specifically designed clinical trials, as it may open perspectives for improving breast cancer treatment.

Benefit of adjuvant chemotherapy in elderly ER-negative breast cancer patients: benefits and pitfalls

Approximately 50% of breast cancer (BC) cases occur in women aged 65 and older, and more than 30% occur in those aged over 70, yet very old (older than 70) patients are under-represented in clinical trials. In the Oxford meta-analysis, the hazard ratios for recurrence and BC mortality in women aged over 70 were 0.88 and 0.87, respectively, suggesting a benefit from chemotherapy in this group of patients as well; however, the large confidence intervals surrounding reductions in this subgroup reflect the small number of older patients recruited in randomized trials in Early Breast Cancer Trialists’ Collaborative Group meta-analyses. If we consider the tumor biology of BC in older adults, we will see that they are more likely to develop a tumor with high estrogen receptor (ER)- and/or progesterone receptor-positive status and a lower proliferative index. However, the biology of these tumors appears to change according to chronological age into aggressive forms diagnosed in these patients as well. This subgroup analysis for the benefit of adjuvant chemotherapy in elderly patients (at least 65 years) is reported in a few studies, even though a limited statistical significance has been revealed. Retrospective evidences suggest that even more aggressive treatments such as taxanes and dose-dense schedule appear feasible (but probably more toxic) in the elderly. Age is no longer considered the only criterion for choosing the right treatment for patients with BC; in fact, functional status and comorbidity have to be taken into consideration as well. Fit elderly patients with more aggressive forms (node-positive and ER-poor disease) seem to obtain the same benefits as younger patients, and thus have to be treated in the same manner.

Steroid hormone status and HER2/neu expression in pregnancy-associated breast cancer

21115 Background: Breast cancer occurring during pregnancy or within the first year after delivery is considered to be a pregnancy-associated breast cancer. Some studies have shown a decreased estrogen receptor-positive and progesterone receptor-positive status in pregnant patients with breast cancer, others, however, have not. Moreover, little information is available about the expression of HER2/neu and about the other human estrogen receptor, estrogen receptor beta (ERbeta) in pregnancy-associated breast cancers. The aim of this work was to determine the extent of the expression of ER alpha and beta, progesterone receptor (PgR) and HER2/neu in pregnancy- associated breast cancer. Material and Methods: Formalin-fixed, paraffin embedded tissues from 16 patients with pregnancy- associated breast cancer were used in this study. Immunostaining for ERalpha, ERbeta and PgR was performed using monoclonal antibodies against ERalpha, PgR (DakoCytomation) and against ERbeta (CHEMICON). The EnVision detection system was applied. Tumors were considered to be expressing receptors if a positive reaction (regardless of intensity) could be identified in at least 10% of cells. The HER-2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Results: 44% of the tumors (7/16) were ERalpha and PgR positive. The expression of ERbeta protein was observed in 94% of pregnancy-associated breast cancers. As many as 50% of ERbeta positive tumors showed no expression of ERalpha. Further, 31% (5 of 16) of breast cancers were HER2/neu positive. Conclusions: This frequent expression of ERbeta in pregnancy-associated breast cancer may result from their prodifferentiative functions which increase during pregnancy and lactation. No significant financial relationships to disclose.

Progesterone receptor status is a significant prognostic variable of progression-free survival in advanced epithelial ovarian cancer.

The purpose of this study was to determine if tumor estrogen receptor (ER) or progesterone receptor (PR) status were significant prognostic variables of survival and progression-free survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III and IV epithelial ovarian cancer. Tumor steroid receptor status was evaluated among 67 consecutive patients who underwent primary surgery from June 1983 through September 1990. Characteristics of receptor-negative and receptor-positive populations were compared by chi-square analysis. Univariate and multivariate analyses were used to identify variables prognostic of survival and progression-free survival. Fifty-one of 67 patients (76.1%) had ER-positive tumors and 31 (46.3%) patients had PR-positive tumors. Significant differences between receptor-positive and receptor-negative populations were not observed. Neither univariate nor multivariate analysis identified ER or PR status as significant prognostic variables of survival (p = 0.93 and p = 0.06, respectively). Progesterone receptor-positive status was a significant prognostic variable of progression-free survival in both univariate (p = 0.03) and multivariate (p = 0.04) analyses even after adjustment for residual disease and patient age. Estrogen receptor status was not a significant prognostic indicator of progression-free survival in either univariate or multivariate analyses. Progesterone receptor-positive tumor status is shown to be an independent prognostic variable of improved progression-free survival among patients with advanced epithelial ovarian cancer.