Ductal Breast Cancer Research Articles

Procena rizika u korelaciji sa gojaznošću i laboratorijskim monitoringom najčešćih tipova karcinoma dojke kod žena u Kantonu Sarajevo

Abstract: Introduction: Breast cancer (BC) is a malignant disease that predominantly affects women, with known genetic components such as mutations in tumor suppressor genes BRCA1 and BRCA2. Other risk factors include unhealthy lifestyles, lack of physical activity, and consumption of alcohol and cigarettes. Aging also plays a role in BC development, with hormonal influences such as estrogen and progesterone promoting cancer growth. Material and Methods: Research was conducted using data collection tools for risk factors and tumor markers from primary healthcare unit records. The sample comprised 200 women, divided into two groups based on BC diagnosis, with complete medical documentation. Male BC cases were excluded. Results: Statistical significance was found between genetic components, family history, aging, obesity, alcohol and cigarette consumption, longer hormone exposure, and female BC development using the Chi-Square test, confirmed by Fisher's Exact test. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were useful for BC screening and metastasis detection, as determined by the One Sample T-test. In Sarajevo Canton, invasive ductal BC was the most common type among women, while lobular carcinoma in situ was the least common. Conclusion: Correlations between risk factors, including aging, unhealthy lifestyles, and hormone exposure, and increased BC risk were confirmed. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were effective in diagnosis, screening, and metastasis detection in females, with sensitivity for regression detection at 81.8% and specificity at 100%.

LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.

Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.

HIF-1 inhibitor PX-478 for cancer therapy and other fields

Hypoxia-inducible factor 1-alpha (HIF-1) is a crucial transcription factor for tumor growth and progression. PX-478, a small molecule HIF-1 inhibitor, has been extensively studied for its potential as an anti-cancer agent in preclinical studies. This paper provides an overview of the current status of PX-478 in cancer treatment, with a focus on its application in treating pancreatic ductal adenocarcinoma (PDAC), lung cancer, breast cancer, glioma, and other kinds of cancer. This article discusses the mechanisms of action, pharmacokinetics, and pharmacodynamics of PX-478, as well as the findings of preclinical and clinical studies conducted to date. The evidence suggests that PX-478 has promising potential as a therapeutic agent for various cancer types. However, further research is needed to fully comprehend the compound's potential benefits and limitations and its optimal clinical application.

Ocular Metastasis from Breast Carcinoma: A Case Report

Background: Eye metastases are a rare event in cancer, patients with breast cancer being the most common primary site (28.5%–58.8%). Patients with ocular metastatic disease can present with a variable clinical picture. Most often presents as a cutaneous or subcutaneous nodule simulating a chalazion but with rapid growth and possible superficial ulceration. The definitive diagnosis is based on the anatomopathological analysis of the lesion. The treatment remains palliative and the prognosis remains poor. Objectives: To further define the histopathologic features of breast carcinoma conducive to orbital metastasis. Methods: We report a case of ocular metastasis in a 46-year-old woman presenting with right eye pain. She had been treated for ductal carcinoma breast cancer with lymph node and bone metastases 5 years ago; a mastectomy with lymph node dissection was performed. The patient consults us for unilateral eyelid swellings evolving for 4 months. On examination, we find well-limited rounded tissue formation in the right upper eyelid ulcerated in places. Oculomotricity was preserved and the rest of the examination was unremarkable. A biopsy of the lesion was carried. Results & Conclusions: Microscopic examination revealed a fibrofatty tissue seat of a tumoral proliferation made of spans and cords, of carcinomatous cells with moderate atypia showing some mitosis figures. The stroma is fibrous. Immunohistochemical studies showed positive immunoreactivity to pancytokeratin, estrogen receptor, progesterone receptor and HER-2, the results were in favor of a metastatic breast carcinoma. In summary, In the case of a metastatic orbital tumor, breast cancer should be considered as a possible source, especially in elderly women. Integrating the clinical information with histopathological findings is warranted.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer

PurposeThe aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC).MethodsData of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001–2015, were analyzed.ResultsILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan–Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08–2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78–0.91), LVSI (hazard ratio 1.75, 95% CI 1.12–2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03–5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02–1.07), LVSI (hazard ratio 3.62, 95% CI 1.92–6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73–0.89).ConclusionThe histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.

Overview of Breast Examination Screening in Labuhan Haji and Pengadangan Village East Lombok Regency

Breast lump is a condition that is often experienced by many women. Breast cancer is ranked second after cervical cancer which is most common suffered by women in the world. This article was written with the aim of early detection of breast lumps and the number of cancer cases. The subject of this study was a ≥18-year-old woman in Labuhan Haji Village and Pengadangan East Lombok Regency. This study used a non-analytical obssional descriptive method using a cross-sectional study. The data that has been obtained will be analyzed descriptively in the form of diagrams. The results of this study can be concluded ingeneral that the type of lump neoplasma found FAM (Fibroadenoma) which is as many as 7 respondents compared to other types of tumors. The type of non-neoplasma lump that was found in this study was Fibrocystic disease or commonly called fibrostic as many as 6 respondents. Mammae aberans were found in this study, namely as many as 2 respondents aged 53 and 60 years. Ductal Carcinoma or breast cancer with ductal type as many as 1 respondent with the age of 60 years. Ginecomastia there was 1 male respondent aged 33 years.Each tumor in the breast has a tendency to occur in a certain age range and each tumor in the breast has a type of benign and malignant tumor.

Neutrophil to lymphocyte ratio does not behave as a good predictor of pathological complete response in breast cancer: A retrospective analysis in the neoadjuvant setting

The breast cancer scenario now requires new solutions for diagnosis and follow-up. The neutrophil-to-lymphocyte ratio (NLR) has been studied as a possible biomarker for predicting prognosis in solid tumors. Due to the ease of obtaining these values from a blood count, NLR could be useful in clinical practice. Therefore, the aim of this study was to analyze the relation between NLR and pathologic complete response (PCR) in breast cancer patients undergoing neoadjuvant treatment. We performed a cross-sectional retrospective study, including ductal breast cancer patients who underwent neoadjuvant chemotherapy and surgery between 2017 and 2019 at the reference hospital institution (n = 1230). Our data were obtained from medical records and laboratory results, so the study was approved by the research ethics committee of the data-providing hospital. Inclusion and exclusion criteria resulted in a final sample of 114 patients. The area under the curve (ROC) showed no statistically significant area (AUC = 0.546) with a CI95% = 0.417–0.676. No relation between NLR and PCR was observed (p = 0.631), indicating that NLR is not a good biomarker for PCR in this population. Regarding the pattern of NLR for different molecular subtypes, no statistical relation was found (p = 0.929). Thus, our study supports the literature that suggests there is no relationship between NLR and PCR.

An association between calcium channel blocker and breast cancer in patients with hypertension: A case-control study

Hypertension is a common disease in clinical practice. Calcium channel blocker (CCB) is an effective antihypertensive agent. There is inconsistent data of an association of CCB and breast cancer in literatures particularly in breast cancer cytology. This study aimed to evaluate this association by a case-control design. The inclusion criteria were adult patients with an age of 18 years or over, diagnosed as hypertension, with a result of mammogram. Those who were pregnant, had no pathological results, or had breast mass prior to diagnosis of hypertension were excluded. Cases defined if the pathological report of any types of breast cancer, while controls were those with benign breast mass. Factors associated with breast cancer were calculated by logistic regression analysis. There were 299 patients met the study criteria. Of those, 100 patients (33.4 %) were in the case group or breast cancer group. There were three factors independently associated with breast cancer. CCB treatment had adjusted odds ratio of 2.25 (95 % confidence interval of 1.36, 3.77), while age of 50 years old or over and hormonal therapy also independently associated with breast cancer with adjusted odds ratios of 3.41 and 2.91, respectively. The CCB group had significantly higher proportion of ductal breast cancer than those who did not take CCB (42.5 % vs 23.8 %, p < 0.001). CCB treatment may be associated with breast cancer especially ductal carcinoma in this study population.

39P Prognostic significance of hypoxic microenvironment biomarkers in invasive ductal breast cancer

39P Prognostic significance of hypoxic microenvironment biomarkers in invasive ductal breast cancer

Repeated electroporation enhances the responsiveness to cisplatin-based intra-tumoral chemotherapy in murine breast cancer: revival of the electro-chemotherapy concept

Background and aims: Electroporation demonstrated certain modulable actions on tumoral cell membrane permeability to increase the intracellular bioavailability of chemotherapeutic drugs. The current in vivo study aimed to investigate the synergic effect of concomitant electroporation application to the intratumoral administration of cisplatin on murine invasive ductal adenocarcinoma breast cancer. Methods: The fragments of the extracted tumor were implanted subcutaneously in healthy female Balb/C mice. Having reached the determined tumoral volume, the mice were randomly divided into five groups, including control, intratumoral cisplatin injection, tumoral electroporation application, electrochemotherapy (ECT), and double course ECT. The normalized tumoral volume and the inhibition ratios were calculated during a 30-day follow-up period. The data were tested by ANONA, and a statistically significant level was set at P&lt;0.05. Results: The inhibition ratio was significantly different between the intra-tumoral cisplatin administration and tumoral electroporation application groups compared to the control group (P&lt;0.05). ECT displayed superior results in comparison to the two later groups (P&lt;0.05). The double-course ECT group even represented a significant difference compared to the ECT group (P&lt;0.05). Conclusion: Concomitant ECT to the cisplatin intratumoral administration indicated contributive anti-tumoral impacts in an in vivo murine model of invasive ductal adenocarcinoma breast cancer. ECT promises further applications to overcome the occurrence of therapeutic resistance to chemotherapeutic drugs.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB)

PurposePrimary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.MethodsThe National Cancer Database (NCDB, 2010–2016) was queried for patients with stage IV HR-positive, HER2-negative invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). We compared clinicopathologic features, primary site surgery rates, and outcomes by histologic subtype. Multivariable Cox proportional hazard models with and without propensity score matching were used for overall survival (OS) analyses.ResultsIn 25,294 patients, primary site surgery was slightly but significantly less common in the 6,123 patients with ILC compared to the 19,171 patients with IDC (26.9% versus 28.8%, p = 0.004). Those with ILC were less likely to receive chemotherapy (41.3% versus 47.4%, p < 0.0001) or radiotherapy (29.1% versus 37.9%, p < 0.0001), and had shorter OS. While mastectomy rates were similar, those with ILC who underwent lumpectomy had significantly higher positive margin rates (ILC 15.7% versus IDC 11.2%, p = 0.025). In both groups, the odds of undergoing surgery decreased over time, and were higher in younger patients with T2/T3 tumors and higher nodal burden.ConclusionLobular histology is associated with less primary site surgery, higher positive margin rates, less radiotherapy and chemotherapy, and shorter OS compared to those with HR-positive HER2-negative IDC. These findings support the need for ILC-specific data and treatment approaches in the setting of metastatic disease.

Breast and colorectal cancer risks among over 6,000 CHEK2 pathogenic variant carriers: A comparison of missense versus truncating variants

Background and aimsHeterozygous truncating pathogenic variants (PVs) in CHEK2 confer a 1.5 to 3-fold increased risk for breast cancer and may elevate colorectal cancer risks. Less is known regarding missense variants. Here we compared the cancer associations with truncating and missense PVs in CHEK2 across breast and colorectal cancer. MethodsThis was a retrospective analysis of 705,797 patients who received single laboratory multigene panel testing between 2013 and 2020. Multivariable logistic regression models determined cancer risk associated with CHEK2 variants as odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for age at diagnosis, cancer history, and ancestry. Breast and colorectal cancer analyses were performed using 6255 CHEK2 PVs, including truncating PVs (N = 4505) and missense PVs (N = 1750). ResultsCHEK2 PVs were associated with an increased risk of ductal invasive breast cancer (p < 0.001) and ductal carcinoma in situ (DCIS) (p < 0.001), with no statistically significant differences when truncating PVs (p < 0.001) and missense PVs (p < 0.001) were evaluated separately. All CHEK2 variants assessed conferred little to no risk of colorectal cancer. ConclusionsIn our large cohort, CHEK2 truncating and missense PVs conferred similar risks for breast cancer and did not seem to elevate risk for colorectal cancer.

A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient

Triple-negative breast cancer (TNBC) is the most aggressive subtype of mammary carcinoma. Here, we describe a case of an 81-year-old female diagnosed with ductal triple negative breast cancer with a germline pathogenic variant in BReast CAncer gene2 (BRCA2). Genetic testing also revealed the presence of four somatic mutations in the ephrin type-A receptor 3 (EphA3), TP53, BRCA1-associated protein (BAP1), and MYB genes. The BRCA2, TP53, and BAP1 gene mutations are highly predictive of a defective homologous recombination repair system and subsequent chromosomal instability in this patient. Coherently, the patient displayed a strong homologous recombination deficiency signature and high tumor mutational burden status, which are generally associated with increased probability of immune neoantigens formation and presentation, and with tumor immunogenicity. Analysis of immune checkpoint revealed high expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), programmed death 1 (PD1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), suggesting that the patient might likely benefit from immunotherapies. Altogether, these findings support an unveiled link between BRCA2 inactivation, HR deficiency and increased expression of immune checkpoints in TNBC. This clinical case highlights the importance of screening TNBC patients for genetic mutations and TMB biomarkers in order to predict the potential efficacy of immunotherapy.

THU495 Glutamate Metabolic Enzymes GLUD1/2 And GPX4 Are Associated with Tumor Size In Black Women With Invasive Lobular Breast Cancer

Abstract Disclosure: T. Young: None. T.C. Abalum: None. N. Hodgins: None. S. Persaud: None. A.I. Fernandez: None. A.O. Olukoya: None. A.M. Rozeboom: None. R.B. Riggins: None. Background and Objective: Invasive Lobular Breast Cancer (ILC) is a special histologic type of breast cancer with unique genetic and biological features. ILC may be less dependent on glucose metabolism than the more common histologic type, invasive ductal breast cancer (IDC), instead relying more on lipid and amino acid metabolism. Our lab has previously published that expression of metabotropic glutamate receptors is increased in more rapidly growing and therapy-resistant cell line models of ILC. We hypothesized that increased expression of glutamate transporters and regulatory enzymes is associated with poor prognostic features. Methods and Analysis: We used multispectral immunohistochemical staining to measure the expression of four functionally related proteins: CD98, GLUD1/2, GPX4, and SLC7A11 in a cohort of 72 women with ILC (23.5% Black, 64.7% White, 11.8% Other). The cohort was in a two-fold redundant tissue microarray (TMA) format comprised of primary tumors collected by the Georgetown University Histopathology and Tissue Shared Resource. SLC7A11 and CD98 form a heterodimer that exports glutamate from, and imports cystine to, the cell. GLUD1/2 are two isoenzymes that convert glutamate into α-ketoglutarate to replenish the TCA cycle, or recycle ammonia to support amino acid synthesis. GPX4 is an enzyme that protects cells from lipid peroxidation-induced death. We compared expression of these proteins with clinical, pathological, and demographic variables (overall survival, hormone receptor expression, tumor size, race, age) using t test/ANOVA, Kaplan-Meier survival analysis, and linear regression. Results: In the 68 evaluable cases, the percentage of ILC tumor cells stained positive for GLUD1/2 and GPX4 was significantly higher than for CD98 or SLC7A11 (P&amp;lt;0.001), so further analyses focused on these. Women with a combination of high (above median) GLUD1/2+ (&amp;gt;49%) and GPX4+ (&amp;gt;54%) expression had a trend toward decreased survival (Hazard Ratio, HR 3.53, P=0.159). GPX4, GLUD1/2, and estrogen receptor (ER) expression were associated with tumor size in the entire cohort (R2 = 0.124, P = 0.041), but this relationship was markedly stronger in Black women (R2 = 0.487, P = 0.040). In univariate analyses, GLUD1/2 (R2 = 0.43, P&amp;lt;0.01) and GPX4 (R2 = 0.27, P&amp;lt;0.05) expression were each associated with tumor size in Black women, but not in the entire cohort. GPX4 expression and tumor size were both significantly higher (P&amp;lt;0.05) in Black women over 60 years of age, compared to those under 60. Conclusion: GLUD1/2 and GPX4 expression may be prognostic in ILC, as our results show that tumor size increases with higher expression of these proteins (especially among Black women). Limitations of this study include small sample size and lack of an independent cohort for validation. Future studies will include analysis of these proteins in a TMA comprised of tissue from women with IDC. Presentation: Thursday, June 15, 2023

S4309 Uncovering the Ulcer: A Rare Case of Invasive Ductal Breast Cancer Metastasis to the Stomach

S4309 Uncovering the Ulcer: A Rare Case of Invasive Ductal Breast Cancer Metastasis to the Stomach

Obesity control and liver health in breast cancer: Normalized hepatic elasticity after ketogenic diet

Most socially significant diseases, including breast cancer, are undeniably linked to obesity. Recently, a positive relationship between excessive weight and increased risk of breast cancer poor outcomes has been proved. Liver integrity is an essential point during chemotherapy. Consequently, a hepatic safe therapeutic approach for managing obesity in patients with breast cancer should be initiated. Our study aimed to assess the impact of the ketogenic diet on body mass index (BMI) and to evaluate its safety on liver function in female patients with breast cancer. The study comprised 520 women with ductal breast cancer who underwent a 60-day modified ketogenic diet. BMI, prothrombin time (PT), activated partial thromboplastin clotting time (aPTT), aspartate aminotransferase to platelet ratio index (APRI), and ultrasound liver elasticity was evaluated before and after the diet. The results showed a significant decrease in BMI and an improvement in ultrasound liver elasticity in all the participants after completing the diet. Before the KD, the participants' median BMI was 35.0 kg/m2, and after the 60-day diet, the median BMI was reduced to 30.0 kg/m2. No significant liver parameter changes were found after the diet. In conclusion, we can safely promote the keto diet amongst individuals with an increased chance of developing breast cancer for a better disease prevention.

Apoptosis evasion and local recurrence after mastectomy and chemotherapy in lobular type breast cancer. A cross-sectional study in a single-center

Link of Video Abstract: https://www.youtube.com/watch?v=Ws-SVwmrhs0Background: Lobular type breast cancer (ILC) was the second most common type after ductal breast cancer. Chemotherapy may be used to lower the risk of recurrence in addition to surgery, which is the main treatment for early-stage breast cancer. Apoptosis is one of the body's techniques for killing cancer cells; thus, cancer cells must be able to evade it to survive. Due to the rarity of the disease, it is uncommon for researchers to investigate ILC, especially at an early stage. This study aimed to determine the mechanism of apoptosis evasion in ILC after mastectomy and chemotherapy who got local recurrence within two years after surgery by analyzing the expression of vimentin, IL 10, and CD 95. Methods: This research was a cross-sectional study of medical records in a single center. The sampling method was total sampling, i.e., all patients underwent a mastectomy and received chemotherapy from January 2014 to December 2019 (5 years). Immunohistochemistry analysis was used to check the vimentin, α-IL10, and CD 95 levels in paraffin blocks from surgical tissues. A chi-square test and a path analysis with a linear regression test were the statistical tests used in this study. Results: Seven samples contained local recurrence, while only six did not. According to statistical tests, the expression of vimentin, IL10, and CD95 between the recurrence and non-recurrence groups was significantly different. The chi-square test showed CD95 is a protective factor for local recurrence (odds ratio [OR] = 0.03, 95% confidence interval [CI] = 0.002-0.68 p =0.001). The multivariate analysis showed that vimentin expression has a significantly strong correlation with IL10 expression (p=0.000); the IL10 expression has a significant negative correlation to CD95 expression (p=0.03); and the CD95 expression was strongly correlated with the local recurrence (p=0.001). Conclusion: Apoptosis evasion had an important role in the local recurrence of ILC after mastectomy and chemotherapy.

Aquaglyceroporins in Human Breast Cancer.

Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.

CD105 expression in cancer-associated fibroblasts: a biomarker for bone metastasis in early invasive ductal breast cancer patients.

Introduction: Bone metastasis is one of the causes that mainly decrease survival in patients with advanced breast cancer. Therefore, it is essential to find prognostic markers for the occurrence of this type of metastasis during the early stage of the disease. Currently, cancer-associated fibroblasts, which represent 80% of the fibroblasts present in the tumor microenvironment, are an interesting target for studying new biomarkers and developing alternative therapies. This study evaluated the prognostic significance of the CD105 expression in cancer-associated fibroblasts in early breast cancer patients. Methods: Immunohistochemistry was used to assess CD105 expression in invasive ductal breast carcinomas (n = 342), analyzing its association with clinical and pathological characteristics. Results: High CD105 expression in cancer-associated fibroblasts was associated with an increased risk of metastatic occurrence (p = 0.0003), particularly bone metastasis (p = 0.0005). Furthermore, high CD105 expression was associated with shorter metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0002, 0.0006, and 0.0002, respectively). CD105 expression also constituted an independent prognostic factor for metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0003, 0.0006, and 0.0001, respectively). Discussion: The high CD105 expression in cancer-associated fibroblasts is an independent prognostic marker for bone metastasis in early breast cancer patients. Therefore, the evaluation of CD105(+) CAFs could be crucial to stratify BCPs based on their individual risk profile for the development of BM, enhancing treatment strategies and outcomes.