Growth hormone stimulates the in vitro development and establishment of Haemonchus contortus in sheep.

The physiologic increase in some sex hormones has been associated with an increase in the parasite load caused by Haemonchus contortus in ewes, especially prolactin. In lambs that are especially susceptible to hemonchosis, the levels of sex hormones are low; in contrast, the levels of another pituitary hormone, growth hormone (GH), which is structurally very similar to prolactin, are high. In this study, the in vitro and in vivo effects of GH on H. contortus larvae development and establishment were evaluated. The addition of 20 ng/mL GH for 5 and 10 days to cultures of H. contortus larvae induced an enlargement (p<0.01) and an L3/L4 molting rate (p<0.03) greater than that of untreated larvae or those treated with other concentrations of the hormone. Flow cytometry showed that 3.8% of the largest and most complex cells of newly obtained larvae of H. contortus were positive for the GH receptor, and by immunofluorescence with confocal microscopy, it was observed that these receptors are located in the intestinal region larvae. In the in vivo assay, the administration of recombinant GH to gonadectomized lambs produced an increase in FEC (p<0.03), the number of female adult worms in the abomasum (p<0.05) and the levels of specific antibodies (p<0.04) in relation to the control lambs; however, it did not affect the fertility of H. contortus females. Although many factors affect the development and implantation of H. contortus in the abomasum of sheep, the results of this study strongly suggest that GH participates in the development and establishment of the parasite in sheep, mainly in young sheep.

A retrospective comparative study on the diagnostic efficacy and the complications: between CassiII rotational core biopsy and core needle biopsy.

Accurate pathologic diagnosis and molecular classification of breast mass biopsy tissue is important for determining individualized therapy for (neo)adjuvant systemic therapies for invasive breast cancer. The CassiII rotational core biopsy system is a novel biopsy technique with a guide needle and a "stick-freeze" technology. The comprehensive assessments including the concordance rates of diagnosis and biomarker status between CassiII and core needle biopsy were evaluated in this study. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed through immunohistochemistry. In total, 655 patients with breast cancer who underwent surgery after biopsy at Sir Run Run Shaw Hospital between January 2019 to December 2021 were evaluated. The concordance rates (CRs) of malignant surgical specimens with CassiII needle biopsy was significantly high compared with core needle biopsy. Moreover, CassiII needle biopsy had about 20% improvement in sensitivity and about 5% improvement in positive predictive value compared to Core needle biopsy. The characteristics including age and tumor size were identified the risk factors for pathological inconsistencies with core needle biopsies. However, CassiII needle biopsy was associated with tumor diameter only. The CRs of ER, PgR, HER2, and Ki67 using Cassi needle were 98.08% (kappa, 0.941; p<.001), 90.77% (kappa, 0.812; p<.001), 69.62% (kappa, 0.482; p<.001), and 86.92% (kappa, 0.552; p<.001), respectively. Post-biopsy complications with CassiII needle biopsy were also collected. The complications of CassiII needle biopsy including chest stuffiness, pain and subcutaneous ecchymosis are not rare. The underlying mechanism of subcutaneous congestion or hematoma after CassiII needle biopsy might be the larger needle diameter and the effect of temperature on coagulation function. In summary, CassiII needle biopsy is age-independent and has a better accuracy than CNB for distinguishing carcinoma in situ and invasive carcinoma.

Role of Hormonal Receptor in Predicting Sentinel Lymph Node Metastasis in Early Breast Cancer.

Background: Sentinel lymph node biopsy is one of the minimally invasive techniques that can confirm the presence of metastasis of regional lymph nodes in cancer. Sentinel lymph node biopsy can be done with a lymph mapping technique using blue-dye, radiotracer, or a combination of both. In developing countries, sentinel lymph node biopsy is often done with a single agent, which is the blue dye. The limitation of conducting SLNB in Indonesia is the availability of patent blue dye and radioisotope tracer. To overcome that, a hormonal receptor is expected to aid in predicting sentinel lymph node metastasis. Objective: The aim of this study was to investigate the hormonal receptor as a prognostic factor of sentinel lymph node metastasis in breast cancer. Methods: This study was conducted in Universitas Sumatera Utara Teaching Hospital with the acknowledgment from the Ethics Committee of the respected hospital by the number of 116/KEP/USU/2020. Total of 51 patients participated in this research. Results: Statistically, the p-value in each immunohistochemistry group is > 0.05 in all ER (+) / PR (+); ER (+) / PR (-); ER (-) / PR (+) groups. This shows that there is no significant relationship between hormonal receptors on sentinel lymph node metastases. Conclusion: The statistical evaluation showed that there is no significant correlation between the hormonal receptor and sentinel lymph node metastasis (p>0.05), but is found clinically significant. Therefore, hormonal receptors should be considered as a predicting factor for sentinel lymph node metastasis.

Correlation Between Age and Hormone Receptor Status in Women With Breast Cancer.

Introduction Breast cancer is a leading cause of death among women. This study aimed to evaluate the association between age and hormonal receptor status (HRS) in women with breast cancer presented at a public hospital in Karachi, Pakistan. Methods A cross-sectional study was conducted at the Department of Medical Oncology, Jinnah Postgraduate Medical Center (JPMC), Karachi, Pakistan, from January 2021 to August 2021. All women of age more than 18 years with a confirmed diagnosis of breast cancer were included in the study using non-random consecutive sampling techniques. Women who underwent artificial menopause or hysterectomy, women who had chemotherapy-induced menopause, and pregnant women were excluded from the study. Data were collected from all patients regarding socio-demographics and tumor characteristics. Immunohistochemistry (IHC) was performed to evaluate the status of hormonal receptors. Results The mean age at the time of presentation of females with breast cancer was 46.57±11.45 years. Among 317 females, 180 females had positive estrogen receptor (ER) expression (56.8%), 173 had positive progesterone receptor (PR) expression (54.6%), and 121 had positive human epidermal growth factor receptor 2 (HER2/neu) expression (38.2%). The highest proportions of positive ER (36.7%), PR (38.2%), and HER/2 neu (37.2%) expression were observed in the age group 41-50 years, respectively. There was a statistically significant association between age and ER expression (p=0.017) and age and PR expression (p=0.003) while no association was found between age and HER/2 neu expression (p=0.335).  Conclusion The present study indicated that the majority of the patients were diagnosed with breast cancer in their 40s. Most of the women in the younger age groups were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while the older aged women were more frequently ER, PR, and HER2/neu positive albeit, the association between age or HER2/neu was not significant.  In short, we can expect that the older aged patients may have better survival rates and patient prognosis. However, this is just a conjecture and further large-scale, multicenter, and long-term studies are required to understand the true relationship between age and patient survival rates. We hope that the current study will serve as a catalyst for future breast-cancer related studies.

Update Breast Cancer 2021 Part 4 - Prevention and Early Stages.

This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this year' s most important study outcomes.

Update Breast Cancer 2021 Part 5 - Advanced Breast Cancer.

Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials.

Presentation and survival by hormonal receptor status in metaplastic breast cancer: A propensity score-matched analysis.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare and aggressive form of breast cancer. The effectiveness of chemotherapy (CT) for MBC remains controversial. The present study aimed to evaluate the efficacy of CT combined hormone receptor (HR) status on MBC patients with high risk (T1-4N2-3M0 and T4N0-1M0) by propensity-score matching (PSM). METHODS: A retrospective study was performed to analyze MBC from the SEER database. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier curve. Cox proportional hazard models were used to assess BCSS. PSM was used to make 1:1 case-control matching. RESULTS: This study identified 3116 patients. The median follow-up time was 44 months (range, 1-321 months). About 62.5 % of patients received CT. 23.0 % of patients were HR-positive. Recurrence risk had a significant difference between the HR-negative and HR-positive groups. In the multivariable Cox regression model, CT had no benefit for MBC patients. HR status was not associated with a better prognosis. In subgroup analysis, the Kaplan-Meier analysis showed that HR-negative MBC with intermediate-risk benefited from CT. For HR-positive MBC, patients with intermediate and high risk also benefited from CT. After PSM, neither CT nor HR status was not related to better BCSS. Moreover, the use of CT could only improve the survival of HR-positive MBC patients with high risk. CONCLUSION: PSM analysis showed that HR status was not associated with a better prognosis. CT was not a significant prognostic factor for prognosis. However, HR-positive MBC patients with high risk might benefit from CT.

Disrupted PGR-B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia.

Background: Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown. Methods: Global RNA sequencing was applied to obtain the transcriptomic profile of endometrial biopsies collected from nonpregnant women who suffer sPE in a previous pregnancy and women who did not develop this condition. Samples were randomized in two cohorts, the training and the test set, to identify the fingerprinting encoding defective decidualization in sPE and its subsequent validation. Gene Ontology enrichment and an interaction network were performed to deepen in pathways impaired by genetic dysregulation in sPE. Finally, the main modulators of decidualization, estrogen receptor 1 (ESR1) and progesterone receptor B (PGR-B), were assessed at the level of gene expression and protein abundance. Results: Here, we discover the footprint encoding this decidualization defect comprising 120 genes-using global gene expression profiling in decidua from women who developed sPE in a previous pregnancy. This signature allowed us to effectively segregate samples into sPE and control groups. ESR1 and PGR were highly interconnected with the dynamic network of the defective decidualization fingerprint. ESR1 and PGR-B gene expression and protein abundance were remarkably disrupted in sPE. Conclusions: Thus, the transcriptomic signature of impaired decidualization implicates dysregulated hormonal signaling in the decidual endometria in women who developed sPE. These findings reveal a potential footprint that could be leveraged for a preconception or early prenatal screening of sPE risk, thus improving prevention and early treatments. Funding: This work has been supported by the grant PI19/01659 (MCIU/AEI/FEDER, UE) from the Spanish Carlos III Institute awarded to TGG. NCM was supported by the PhD program FDGENT/2019/008 from the Spanish Generalitat Valenciana. IMB was supported by the PhD program PRE2019-090770 and funding was provided by the grant RTI2018-094946-B-100 (MCIU/AEI/FEDER, UE) from the Spanish Ministry of Science and Innovation with CS as principal investigator. This research was funded partially by Igenomix S.L.

Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+/HER2- Early Breast Cancer.

Molecular factors that drive metastasis in premenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), early breast cancer (EBC) are largely unknown. To identify markers/signatures contributing to metastasis, we analyzed molecular changes in tumors from premenopausal patients who developed metastasis (M1) and who did not (M0). Ninety-seven premenopausal patients with HR+/HER2- EBC were included (M1, n = 48, median distant metastasis-free survival (DMFS): 54 (7-184) months; M0, n = 49, median follow-up: 149 (121-191) months). Gene expression profiling on tumor RNA (Breast Cancer 360TM panel, Nanostring) was performed, followed by comprehensive bioinformatic and statistical analyses. Significantly enhanced ROR (risk of recurrence) scores and reduced signature scores of PGR (progesterone receptor), claudin-low, and mammary stemness were determined in M1. These differences were significantly associated with shorter DMFS in univariate survival analyses. Gene set enrichment analysis showed an enriched mTORC1 pathway in M1. Moreover, a metastasis signature of 19 differentially expressed genes (DEGs) that were DMFS-related was defined. Multivariate analysis including the four signatures, 19 DEGs, pN, and pT status, identified LRP2, IBSP, and SCUBE2 as independent prognostic factors. We identified prognostic gene signatures and single-gene markers for distant metastasis in premenopausal HR+/HER2- EBC potentially applicable in future clinical practice.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

BACKGROUND: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. METHOD: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. RESULTS: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. CONCLUSION: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Single Hormone Receptor-Positive Metaplastic Breast Cancer: Similar Outcome as Triple-Negative Subtype.

Background: Metaplastic breast cancer (MBC) is a rare and aggressive subtype of the breast. To understand the characteristics and prognosis of single hormone receptor-positive (HR+) MBC (estrogen receptor-positive [ER+]/progesterone receptor-negative [PR-] and ER-/PR+), we compared these tumors to double HR+ tumors as well as HR- tumors. Patients and Methods: The Surveillance, Epidemiology, and End Results database was used to analyze MBC between 1975 and 2016. The effect of HR status was evaluated using a multivariate Cox regression model. Results: We included 3369 patients with a median follow-up time of 42 months (range 0-322 months). In this study, 280 (8.3%) cases were double HR+ tumors, 2597 (77.1%) were double HR- tumors, and 492 (14.6%) cases were single HR+ tumors, of which 159 (4.7%) cases were ER-/PR+ tumors and 333 (9.9%) were ER+/PR- tumors. On multivariate Cox analysis, the prognosis was related to age, race/ethnicity, tumor grade, TNM stage, and surgery. HR status remained no impact on breast cancer-specific survival (BCSS). In the Kaplan-Meier curve, HR status was not associated with better BCSS or overall survival (OS). In patients without HER2 overexpression, the BCSS and OS of ER+/PR- and ER-/PR+ tumors were not significantly different from that of ER-/PR- and ER+/PR+ tumors. The difference remains no significant in patients with HER2 overexpression. Conclusions: In comparison with both ER-/PR- and ER+/PR+ tumors, we have identified clinically and biologically distinct features of single HR+ tumors. In patients with or without HER2 overexpression, the prognosis of single HR+ tumors was similar to ER-/PR- and ER+/PR+ tumors.

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer.

BACKGROUND: In patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas. METHODS: This retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients' estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations. RESULTS: A total of 228 patients were included, and the median patient age was 44 (range, 25-54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4-683) pg/mL and 7.3 (range, 0.4-88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0-52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one. CONCLUSIONS: The 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use.

Characteristics of Invasive Breast Cancer Detected by Digital Breast Tomosynthesis on Screening and Diagnostic Mammograms.

OBJECTIVE: To determine whether there is added benefit for 3D mammography in the context of screening and diagnostic imaging, particularly relating to known prognostic characteristics, including histopathology, receptor status, and axillary lymph node involvement. METHODS: An institutional review board-approved retrospective review was performed of our mammography and pathology databases from October 2012 to May 2015 to identify biopsy-proven invasive breast carcinoma detected on screening and diagnostic mammograms by 2D plus 3D (2D + 3D) imaging. Percentages of cancer detection by 2D and 3D were compared. Correlation with histopathology and lymph node status was analyzed. RESULTS: Of 53 cancers diagnosed on 12 543 screening mammograms, 36 (67.9%) were better visualized on 3D (not visualized, equivocal, or only seen in retrospect on 2D). Of the 62 cancers diagnosed on 4090 diagnostic mammograms, 24 (38.7%) cancers were better detected on 3D. A statistically significant greater number of cancers were better detected on 3D in the screening compared to the diagnostic mammograms (67.9% vs 38.7%, P < .05). A significantly higher frequency of less aggressive tumors (grade I and grade II, positive estrogen/progesterone receptor, Her2 negative) was detected by 3D, with higher significance in the screening population. Additionally, there was a higher frequency of positive axillary lymph nodes in cancers detected by 3D in the screening group. CONCLUSION: Three-dimension increases invasive breast cancer detection, particularly pathologically less aggressive tumors, in both screening and diagnostic mammograms with more benefit for the screening population. Three-dimensional mammography detected more breast cancer associated with metastatic axillary lymph nodes in the screening population.

Association Between Neutrophil-Lymphocyte Ratio and Oncotype Dx Recurrence Score in Early-Stage Hormonal Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer.

PURPOSE: The correlation between the preoperative neutrophil-to-lymphocyte ratio (NLR) and Oncotype DX® (ODX) recurrence score (RS) has not yet been established. We aimed to investigate the association between NLR and ODX RS in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (BC). PATIENTS AND METHODS: This retrospective study included consecutive patients with HR+/HER2-, node-negative primary BC who underwent surgical tumor resection from 2011 to 2019. Receiver operating characteristic curve analysis was used to obtain an optimal NLR cutoff value. Logistic regression analyses were used to estimate associations between various parameters and ODX RS. Furthermore, the factors significantly associated with the ODX RS in multivariable analysis were incorporated in a separate model and estimated using logistic regression. RESULTS: A total of 160 patients were enrolled. The optimal preoperative NLR cutoff was 2.15. Multivariable analysis revealed that NLR and tumor grade (G1/G2 vs G3) were independent predictive factors of high RS cutoff (≥26). Moreover, including the two variables yielded a stronger association; patients with low NLR and low-grade tumors were unlikely to have high RS (≥26; odds ratio [OR] = 0.03, 95% confidence interval [CI]: 0.006-0.154; p < 0.001). Conversely, the presence of any of the following factors made patients unlikely to have low RS (<16; OR = 0.34, 95% CI: 0.16-0.73; p = 0.006): high NLR, high grade, or high Ki-67 levels (>20). CONCLUSION: NLR is a promising independent predictor of RS. Furthermore, in addition to tumor grade and Ki-67 level, they together are also a potential indicator of high and low RS. However, further studies are required to validate this hypothesis.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer.

HER2-positive breast cancer accounts for 18-20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

Inorganic arsenic methylation capacity and breast cancer by immunohistochemical subtypes in northern Mexican women.

BACKGROUND: Previously we reported that inorganic arsenic (iAs) methylation capacity was associated with breast cancer (BC). BC risk factors may vary according to immunohistochemical subtype. Here we explored the relationships between the capacity to methylate iAs and the risk of BC by subtype. METHODS: A population-based case-control study was performed in northern Mexico. Patients with available information about BC subtypes (n = 499) were age-matched with healthy controls. Sociodemographic, reproductive, and lifestyle characteristics were obtained. Tumor marker information was obtained from medical records. Cases were classified as HR+ [estrogen receptor (ER+) and/or progesterone (PR+), and human epidermal growth factor receptor 2 (HER2-)], HER2+, or triple negative (TN). Urinary arsenic species were determined by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and methylation capacity parameters calculated. Conditional logistic regression models were used to estimate BC risk by subtypes. RESULTS: Urinary total arsenic varied from 0.60 to 303.29 µg/L. A significant positive association was found between % monomethylarsonic acid (%MMA) and HR + BC: one percent increase resulted in OR%MMA continuous = 2.73, 95% CI: 1.48, 5.05), and this association remained even when %iAs or % dimethylarsinic acid (%DMA) were added to the models with %MMA. MMA/iAs was positively associated with HR + BC (ORMMA/iAs continuous = 2.03, 95% CI: 1.33-3.10). A significant negative association was observed between DMA/MMA and HR + BC (ORDMA/MMA continuous = 0.43, 95% CI: 0.26, 0.71). MMA/iAs was positively associated with TN BC (OR MMA/iAs continuous = 4.05; 95% CI: 1.63, 10.04). CONCLUSION: Altered iAs methylation capacity resulting in higher %MMA was associated with HR+ and TN BC but not with HER2+. MMA is the iAs metabolite more likely to be related to BC. Further research is needed to confirm these results and elucidate the underlying biological mechanisms.

Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.

PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.

Patrón de recurrencia local en el carcinoma ductal in situ de mama según su inmunofenotipo / Pattern of local recurrence in ductal carcinoma in situ according to the inmunophenotype

Introducción En el carcinoma intraductal o carcinoma ductal in situ (cdis), la sobreexpresión del her2 neu (her2 neu+), alcanza un 60 a 70% de los casos y se asocia con la presencia de alto grado nuclear, comedo-necrosis y baja expresión de receptores hormonales. La asociación entre la sobreexpresión de her2 neu, receptor de estrógeno negativo (re) y alta expresión de factor de proliferación Ki67 (>14%) en pacientes con cdis tendría mayor riesgo de recurrencia local. Objetivos Determinar la frecuencia de sobreexpresión del factor de membrana epidérmico her2 neu en los carcinomas ductales in situ de mama y su relación con la recurrencia local de la enfermedad. Asimismo, determinar la relación entre la sobreexpresión del her2 neu y la supervivencia libre de enfermedad (sle), la supervivencia global (sg), los receptores hormonales y Ki67, y el tipo de recurrencia. Material y método Estudio retrospectivo que incluye pacientes con diagnóstico de cdis de mama en el Servicio de Mastología del Hospital Británico de Buenos Aires operadas entre enero de 2006 y diciembre de 2014. Las variables analizadas fueron la edad, el estado menopáusico, la forma de presentación, el tratamiento quirúrgico y adyuvante, el diagnóstico anátomo-patológico y la inmunohistoquímica, la supervivencia libre de enfermedad y la supervivencia global. Resultados Se incluyeron en el estudio 252 pacientes que cumplían con los criterios de inclusión, agrupándolas según la sobreexpresión o no del receptor de membrana her2 neu en el resultado anátomo-patológico de la pieza operatoria. Sobreexpresaron el receptor de membrana her2 neu (her2 neu+) 86 pacientes (34,1%), mientras que 166 pacientes (65,9%) fueron her2 neu negativo (her2 neu­). Se observó menor número de re negativo en el grupo her2 neu­ (8,4%) vs las pacientes del grupo her2 neu+ (39,5%) (p<0,001). Se registraron 24 recurrencias locales (9,52%), 8 de ellas del grupo her2 neu­ (4,8%) y las 16 restantes del grupo her2 neu+ (18,6%). Se halló una asociación estadísticamente significativa entre la recurrencia local y la sobreexpresión de her2 neu: p=0,04. Conclusiones Se encontró que la sobreexpresión del her2 neu se asoció a una mayor tasa de recurrencia local del carcinoma ductal in situ, con una menor sle en este grupo. También hubo un mayor número de tumores con receptores hormonales negativos en el grupo her2 neu+. En cuanto a la sg, no encontramos diferencias entre ambos grupos

Introduction The incidence of human epidermal growth factor 2 (her2 neu) overexpression or amplification in ductal carcinoma in situ (dcis) is between 60 to 70%, and is associated with the presence of high nuclear grade, comedonecrosis, and low expression of hormonal receptors. There is a higher risk of local recurrence in patients with dcis that overexpress her2 neu, have negative estrogen receptor and high Ki67 (>14%). Objectives Identify patients diagnosed with dcis that overexpressed her2 neu, and its association with local recurrence. Likewise, determine the relationship between her2 neu amplification and disease free survival (dfs), overall survival (os), and expression of hormonal receptors, Ki67 and the type of recurrence. Materials and method Retrospective study, that included patients with dcis diagnosed and surgically treated in the Breast Service of Hospital Britanico de Buenos Aires between January 2006 and December 2014. Demographic information analyzed included age, menopausal status, type of presentation, surgery and adjuvant therapy, histopathological analysis and immunohistochemistry (ihc), dfs and os. Results 252 patients were included and divided in two groups according to the her2 neu expression in the histopathologic result after surgery. The overexpression of her2 neu (her2 neu positive/her2 neu+) was found in 86 patients (34.1%) and 166 patients (65,9%) were her2 neu negative (her2 neu­). In the her2 neu­ group we found less negative estrogen receptor (8.4%) than in the her2 neu+ group (39.5%) (p<0.001). There were 24 local recurrence (9.52%): 8 were her2 neu­ (4.8%) and 16 were her2 neu+ (18.6%). The association between local recurrence and her2 neu overexpression was statistically significant in our analysis: p=0.04. Conclusions The her2 neu overexpression was related with a higher recurrence rate, less dfs. There was also a higher number of tumors with negative estrogen receptor that overexpressed her2 neu. No difference was found in the os between groups

The Impact on the Long-term Outcomes of Hormonal Status After Hepatic Resection for Breast Cancer Liver Metastases.

BACKGROUND/AIM: Breast cancer remains one of the most frequently encountered malignancies worldwide, which is in most cases diagnosed in early stages of disease. However, although surgery and adjuvant oncological treatment are performed with curative intent, a certain number of cases will develop distant metastases. In cases presenting oligometastatic disease, surgery might be tempted in order to maximize the benefit in terms of survival. The aim of this paper was to identify which cases could benefit most after liver resection for breast cancer liver metastases. MATERIALS AND METHODS: The study included 67 patients submitted to surgery for breast cancer liver metastases between 2003 and 2017 in the "Dan Setlacec" Center of Gastrointestinal Diseases and Liver Transplantation, Fundeni Clinical Institute. RESULTS: Patients diagnosed with hormone-positive breast tumors reported a significantly higher disease-free and overall survival after resection of the primary tumor. After resection for breast cancer liver metastases, patients presenting hormone receptors at the level of the metastatic sites also experienced a better outcome when compared to those in which hormonal receptors were absent. However, the difference was not statistically significant. CONCLUSION: Liver resection for breast cancer liver metastases seems to be associated with the best outcomes in terms of survival in patients presenting positive hormonal receptors status.