Metastatic Breast Research Articles

Bone metastasis in endocrine-related cancer: unravelling invasion and destruction.

Bone is a common and debilitating site for metastatic cancer cell expansion. Skeletal metastasis is a multistage process, with primary stages of circulating tumour cells, progressing to a dormant state in vasculature and bone marrow niches, followed by tumorigenic reactivation, proliferation, and finally bone destruction. The frequency of bone metastasis is reconciled in Paget's "seed and soil" hypothesis, where a conducive microenvironment (bone niche) is essential for cancer cell colonisation. Cancer cells can mimic bone cells (osteomimicry) and interact with the bone marrow's vascular architecture, utilising pathways akin to hematopoietic stem cell expansion. Current research suggests that each phase of bone metastasis is associated with specific gene expression and protein abundance patterns. For example, E-selectin, CXCR-4, and CXCL-12 are crucial for cancer cell homing, dormancy, and colonisation of bone tissue. In contrast, different primary cancers appear to have unique staging profiles. In prostate cancer, dormancy is modulated by the CXCR-4/CXCL-12, ANXA2/CXCL12, and GAS6 pathways, while in breast cancer, dormancy involves ERK1/2, p38, MSK1, LIF, BMP-7, TGF-β1/2, and bone resorption factors. Conversely, osteoblastic metastasis in both breast and prostate cancers is characterised by ET-1, Dkk1 suppression, and the release of IL-6, MCP-1, VEGF, FGF, and IGF, while osteolytic metastasis primarily depends on PTHrP, RANKL, OPG, TGF-β, IGF, TNF-α, IL-1, and IL-7. Understanding the complex molecular mechanisms facilitating cancer cell colonisation and expansion in bone tissues is essential for developing effective treatments to prevent bone metastases . In this review, we discuss current theories linking bone remodelling with bone.

Unusual breast metastasis from follicular thyroid carcinoma 17 years after thyroidectomy: a case description and literature analysis.

Unusual breast metastasis from follicular thyroid carcinoma 17 years after thyroidectomy: a case description and literature analysis.

Breast metastasis from primary renal cell carcinoma, ten years after nephrectomy

BackgroundMetastasis to the breast from non-breast tumors is uncommon, and breast metastasis from renal cell carcinoma (RCC) is extremely rare. Despite the high incidence of primary breast cancer, it is important to consider metastasis from other cancers in patients with a history of malignancies.Case presentationA 60-year-old female with a history of right nephrectomy for RCC 10 years prior, who had missed follow-up for 7 years, presented with hepatic metastases that had been under treatment for the past 2 years. During routine follow-up, a small lesion in her right breast was incidentally found on chest-computed tomography. She was referred for further imaging, and mammography and ultrasound revealed a BI-RADS 3 lesion. Six months later, the lesion had grown rapidly, and a follow-up CT showed a tripling in size along with an increase in the size and number of hepatic metastases. A biopsy of the breast lesion confirmed it as metastatic RCC.ConclusionsThis case is unusual due to the rare site of metastatic spread. Physicians should be aware of considering metastasis when new breast lesions appear in patients with a history of RCC. A biopsy should be considered essential in such cases to ensure accurate diagnosis.

Abstract A035: Infection of primary mammary fibroblasts with cytomegalovirus coordinately increases autotaxin-lysophosphatidate-inflammatory signaling, which could increase breast cancer metastasis

Abstract Background: Metastatic breast cancer is the most prevalent cause of mortality by cancer-related deaths in women. Our group showed that the 63% of Canadian breast cancer patients who were infected with CMV were 5.6-times more likely to develop Stage IV cancers with reduced relapse-free survival. Also, the metastatic phenotype of breast tumors and the number and sizes of lung metastases were increased in mice with latent infections. Fibroblasts are important sites of CMV infection. Cancer-associated fibroblasts (CAFs) are also major sites of autotaxin (ATX) secretion in breast tumors, whereas ATX production and CMV infection in breast cancer cells is negligible. ATX produces lysophosphatidate (LPA), which increases inflammatory cytokine production that stimulates further ATX secretion in a feedforward cycle. LPA promotes breast tumor growth and metastasis by signaling through six G protein-coupled receptors. Signaling is terminated by lipid phosphate phosphatases (LPPs)-1 and -3, which degrade LPA and are decreased in breast tumors. Hypothesis: Breast cancer metastasis could be increased by active CMV infection of CAFs through increased inflammation and LPA signaling. Results: Quiescent fibroblasts isolated and cultured from mammary tissue of non-tumor bearing mice (n>3) produced negligible quantities of ATX. LPA signaling was coordinately promoted in these primary fibroblasts infected for 48 h with 1 MOI of mouse CMV (n=3) with a 5-fold increase in mRNA for ATX (p=0.008), increased mRNAs for LPA2,3,4 receptors (p<0.05) and decreased mRNA expressions for LPP1 and LPP3 (p<0.05). An increase in the secretion of granulocyte monocyte-colony stimulating factor of 548 pg/ml (p=0.01) and Interleukin-6 by 8307 pg/ml (p=0.03) was observed post infection (n=5), thus creating a pro-inflammatory environment. Increased mRNA expression of fibroblast markers, including alpha-smooth muscle actin (p=0.005), fibroblast-associated protein (p=0.007), epidermal growth factor receptor (EGFR) (p=0.001) and transforming growth factor- ß receptor 1 (TGF-ßR1) (p=0.03) was also observed post-infection (n=3). The results were analyzed by student’s t-test. Assessment of these factors in breast cancer patients (n=1100) using the Tumor Immune Estimation Resource Analysis showed a positive correlation in the expression of EGFR and TGF-ßR1 with the LPA3,4 receptors (p<0.05). Conclusion: The changes in expression of ATX, LPA receptors and LPPs in CMV- infected fibroblasts are consistent with increased metastasis. Our results show that mCMV infection of primary mammary fibroblasts dramatically reprograms them to express CAF-like properties and promotes ATX-LPA-inflammatory signaling. CAFs are a major constituent of the tumor stroma. They promote tumor progression by secreting factors such as ATX, which increases metastasis, fibrosis and favors immunosuppression. Our results support the use of pharmacological agents to block signaling by the ATX-LPA-inflammatory cycle to treat breast and other cancers, especially for the majority of patients who are infected with CMV. Citation Format: Humayara Khan, Xiaoyun Tang, Frank Wuest, David N. Brindley, Denise G. Hemmings. Infection of primary mammary fibroblasts with cytomegalovirus coordinately increases autotaxin-lysophosphatidate-inflammatory signaling, which could increase breast cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A035.

Breast metastasis from large cell neuroendocrine carcinoma of the lung: a case report

BackgroundPrimary breast carcinoma is far more common than breast metastases. Common breast metastases usually come from lymphoma, leukemia, melanoma, and ovarian cancers. Breast metastases from neuroendocrine carcinomas are considered an exceeding rare entity. It has been reported in the literature that the pathological presentation of this particular metastatic tumor is very challenging as it shares many morphological characteristics with primary breast carcinoma.Case presentationWe report a case of a patient with large cell neuroendocrine carcinoma of the lung metastasizes to both breasts. The patient was initially presented with brain metastasis of unknown origin. Further radiological imaging workup showed multiple bilateral breast masses and bilateral lymphadenopathy, which raised concern for secondary lymphoma of the breast. The histopathology of this case was challenging, particularly when triple negative invasive ductal carcinoma diagnosis had been made. Multidisciplinary meetings between medical oncologists, radiologists, and pathologists profoundly helped confirming the diagnosis of metastatic large cell neuroendocrine tumor to the breast.ConclusionLarge cell neuroendocrine carcinoma of the lung is a relatively uncommon diagnosis with generally poor prognosis. Large cell neuroendocrine carcinoma that metastasizes to the breast is even scarcer. Correlation between clinical assessment, radiological imaging, and pathological evaluation is the key in making such an unusual and complex diagnosis. Additionally, radiologists should be aware of metastatic presentations of the breast and avoid confusion with mimicking benign entities or primary breast carcinomas.

NSDHL contributes to breast cancer stem-like cell maintenance and tumor-initiating capacity through TGF-β/Smad signaling pathway in MCF-7 tumor spheroid

BackgroundNAD(P)-dependent steroid dehydrogenase-like protein (NSDHL), which is involved in breast tumor growth and metastasis, has been implicated in the maintenance of cancer stem cells. However, its role in regulating breast cancer stem-like cells (BCSCs) remains unclear. We have previously reported the clinical significance of NSDHL in patients with estrogen receptor-positive (ER +) breast cancer. This study aimed to elucidate the molecular mechanisms by which NSDHL regulates the capacity of BCSCs in the ER + human breast cancer cell line, MCF-7.MethodsNSDHL knockdown suppressed tumor spheroid formation in MCF-7 human breast cancer cells grown on ultralow-attachment plates. RNA sequencing revealed that NSDHL knockdown induced widespread transcriptional changes in the MCF-7 spheroids. TGF-β signaling pathway was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (fold change ≥ 2, P ≤ 0.05) identified in NSDHL-knockdown MCF-7 spheroids compared with the control. In orthotopic tumor models injected with NSDHL-knockdown MCF-7 spheroids, tumor initiation and growth were strongly suppressed compared with those in the control.ResultsBCSC populations with CD44+/CD24- and CD49f+/EpCAM + phenotypes and high ALDH activity were decreased in NSDHL-knockdown MCF-7 spheroids and xenograft tumors relative to controls, along with decreased secretion of TGF-β1 and 3, phosphorylation of Smad2/3, and expression of SOX2. In RNA-sequencing data from The (TCGA) database, a positive correlation between the expression of NSDHL and SOX2 was found in luminal-type breast cancer specimens (n = 998). Our findings revealed that NSDHL plays an important role in maintaining the BCSC population and tumor-initiating capacity of ER-positive MCF-7 spheroids, suggesting that NSDHL is an attractive therapeutic target for eliminating BCSCs, thus preventing breast cancer initiation and progression.ConclusionsOur findings suggest that NSDHL regulates the BCSC/tumor-initiating cell population in MCF-7 spheroids and xenograft tumors.

Screening and validating the optimal panel of housekeeping genes for 4T1 breast carcinoma and metastasis studies in mice

The 4T1 model is extensively employed in murine studies to elucidate the mechanisms underlying the carcinogenesis of triple-negative breast cancer. Molecular biology serves as a cornerstone in these investigations. However, accurate gene expression analyses necessitate data normalization employing housekeeping genes (HKGs) to avert spurious results. Here, we initially delve into the characteristics of the tumor evolution induced by 4T1 in mice, underscoring the imperative for additional tools for tumor monitoring and assessment methods for tracking the animals, thereby facilitating prospective studies employing this methodology. Subsequently, leveraging various software platforms, we assessed ten distinct HKGs (GAPDH, 18 S, ACTB, HPRT1, B2M, GUSB, PGK1, CCSER2, SYMPK, ANKRD17) not hitherto evaluated in the 4T1 breast cancer model, across tumors and diverse tissues afflicted by metastasis. Our principal findings underscore GAPDH as the optimal HKG for gene expression analyses in tumors, while HPRT1 emerged as the most stable in the liver and CCSER2 in the lung. These genes demonstrated consistent expression and minimal variation among experimental groups. Furthermore, employing these HKGs for normalization, we assessed TNF-α and VEGF expression in tissues and discerned significant disparities among groups. We posit that this constitutes the inaugural delineation of an ideal HKG for experiments utilizing the 4T1 model, particularly in vivo settings.

Cisplatin-functionalized dual-functional bone substitute granules for bone defect treatment after bone tumor resection

Invasive bone tumors pose a significant healthcare challenge, often requiring systemic chemotherapy and limb salvage surgery. However, these strategies are hampered by severe side effects, complex post-resection bone defects, and high local recurrence rates. To address this, we developed dual-functional bone substitute biomaterials by functionalizing commercially available bone substitute granules (Bio-Oss® and MBCP®+) with the established anticancer agent cisplatin. Physicochemical characterization revealed that Bio-Oss® granules possess a higher surface area and lower crystallinity compared to MBCP®+ granules, which enhances their capacity for cisplatin adsorption and release. In co-cultures with metastatic breast and prostate cancer cells (MDA-MB-231 and PC3) and bone marrow stromal cells (hBMSCs), cisplatin-functionalized granules and their releasates exhibited dose-dependent cytotoxic effects on cancer cells while having less impact on hBMSCs. Furthermore, investigations on the mechanism of action indicated that cisplatin induced significant cell cycle arrest and apoptosis in MDA-MB-231 and PC3 cells, contrasting with minimal effects on hBMSCs. In a rat femoral condyle defect model, cisplatin-functionalized granules did not evoke adverse effects on bone tissue ingrowth or new bone formation. Importantly, local application of cisplatin-functionalized granules resulted in negligible cisplatin accumulation without signs of apoptotic damage in kidneys and livers. Taken together, we here provide hard evidence that cisplatin-functionalized granules maintain a favorable balance between biosafety, anticancer efficacy, and bone regenerative capacity. Consequently, loading granular bone substitutes with cisplatin holds promise for local treatment of bone defects following bone tumor resections, presenting a safe and potentially more effective alternative to systemic cisplatin administration. Statement of SignificanceCurrent treatments in combating malignant bone tumors are hampered by severe side effects, high local tumor recurrence, and complex bone defects after surgery. This study explores a facile manufacturing method to render two types of commercially available bone substitute granules (Bio-Oss® and MBCP®+) suitable for local delivery of cisplatin. The use of cisplatin-functionalized granules has shown promising results both in killing cancer cells in a dose-dependent manner and in aiding bone regeneration. Importantly, this local treatment strategy avoids the systemic toxicity associated with traditional chemotherapy to excretory organs. This dual-functional strategy represents a significant advancement in bone cancer treatment, offering a safe and more efficient alternative that could improve outcomes for patients following bone tumor resection.

Detection of brain metastases from blood using Brain nanoMET sensor: Extracellular vesicles as a dynamic marker for metastatic brain tumors

Brain metastases account for a significant number of cancer-related deaths with poor prognosis and limited treatment options. Current diagnostic methods have limitations in resolution, sensitivity, inability to differentiate between primary and metastatic brain tumors, and invasiveness. Liquid biopsy is a promising non-invasive alternative; however, current approaches have shown limited efficacy for diagnosing brain metastases due to biomarker instability and low levels of detectable tumor-specific biomarkers. This study introduces an innovative liquid biopsy technique using extracellular vesicles (EVs) as a biomarker for brain metastases, employing the Brain nanoMET sensor. The sensor was fabricated through an ultrashort femtosecond laser ablation process and provides excellent surface-enhanced Raman Scattering functionality. We developed an in vitro model of metastatic tumors to understand the tumor microenvironment and secretomes influencing brain metastases from breast and lung cancers. Molecular profiling of EVs derived from brain-seeking metastatic tumors revealed unique, brain-specific signatures, which were also validated in the peripheral circulation of brain metastasis patients. Compared to primary brain tumor EVs, we also observed an upregulation of PD-L1 marker in the metastatic EVs. A machine learning model trained on these EV molecular profiles achieved 97% sensitivity in differentiating metastatic brain cancer from primary brain cancer, with 94% accuracy in predicting the primary tissue of origin for breast metastasis and 100% accuracy for lung metastasis. The results from this pilot validation suggest that this technique holds significant potential for improving metastasis diagnosis and targeted treatment strategies for brain metastases, addressing a critical unmet need in neuro-oncology.

Factors associated with physical activity in individuals with metastatic cancer: a UK cross-sectional survey.

Physical activity is safe and feasible for individuals with metastatic cancer and may support symptom management. We investigated the extent to which individuals with metastatic cancer are meeting the World Health Organisation (WHO) moderate-vigorous physical activity (MVPA) guideline, factors associated with meeting the guideline, and perceptions about physical activity and receiving physical activity advice. Data were from UK adults with metastatic breast, prostate, or colorectal cancer who completed the Healthy Lifestyle After Cancer survey (N = 588). Self-reported clinical, demographic, and physical activity (Godin Leisure-Time Exercise Questionnaire) data were collected. Logistic regression models assessed whether clinical and demographic factors were associated with meeting the MVPA guideline. Most (59%) individuals with metastatic cancer were not meeting the WHO guideline of 150min of MVPA per week. Adjusting for cancer type, the odds of meeting the MVPA guideline were lower for unemployed individuals (OR = 0.47, 95% CI = 0.23-0.77) and ethnic minorities (OR = 0.44, 95% CI = 0.22-0.89), but higher for those with a university education (OR = 1.89, 95% CI = 1.0-3.57). Most (63.5%) participants felt they should be doing more physical activity. However, 70.1% did not receive any physical activity advice or support, despite 73.6% wanting to receive it. People with metastatic cancer may need further support to address inadequate levels of physical activity. The differences observed between demographic sub-groups suggest this may be more beneficial for those less likely to engage in physical activity. Individuals with metastatic cancer are likely to benefit from increased physical activity support, which considers the needs of diverse demographic groups.

Stereotactic Radiosurgery for Intracranial Breast Metastases: A Systematic Review and Meta-Analysis

Background/Objectives: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. Methods: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes of stereotactic radiosurgery on intracranial metastases from breast cancer were included. Adverse events were defined as leptomeningeal disease, radiation necrosis, seizure, and headache. The pooled estimate was calculated using the DerSimonian and Laird approach. Results: Sixteen studies encompassing 1228 patients met the inclusion criteria. Our analysis revealed a median survival duration of 13.1 ± 3.8 months and a pooled 1-year overall survival rate of 53.1% after SRS treatment. There was a 29% local recurrence rate at 1 year and a 35% overall distant recurrence rate. In addition, our analysis found a relatively low rate of acute adverse events at 15.5%. Conclusions: SRS demonstrates promising efficacy and safety in managing intracranial metastases from breast cancer, with a favorable toxicity profile.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor A (VEGF-A) expressions in Ethiopian female breast cancer and their association with histopathologic features.

Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGF) play important role in breast tumor growth, invasion, metastasis, patient survival and drug resistance. The aim of this study was to evaluate the protein expression status of EGFR and VEGF-A, as well as their association with hormone receptor status and histopathological characteristics in the invasive type of female breast cancer among Ethiopians. The primary breast tumor tissues were obtained from 85 Ethiopian invasive breast cancer cases that underwent modified radical mastectomy (MRM) from June 2014 to June 2015. Their FFPE blocks were analyzed for EGFR and VEGF protein expressions using immunohistochemical techniques. The expressions were also correlated with histopathologic features. Epidermal growth factor receptor over-expression was observed in 22% of the tumor samples. VEGF-A expression was negative in 13.41%, low in 63.41%, moderate in 20.73%, and high in 2.44%. EGFR expression, but not VEGF-A, showed a significant inverse correlation with both estrogen receptor (ER) (P = 0.01) and progesterone receptor (PR) statuses (P = 0.04). EGFR and VEGF expressions did not show significant association with tumor size, grade, lymph node status or age at diagnosis. Epidermal growth factor receptor expression was most likely associated with ER and PR negative tumors. Assessments of multiple molecular markers aid to understand the biological behavior of the disease in Ethiopian population. It might also help to predict which group of patients might get more benefit from the selected treatment strategies and which are not.

Mammary Carcinoma Metastasizing to Renal Cell Carcinoma: A Case Report

Abstract Introduction/Objective The simultaneous occurrence of multiple primary cancers is rare, and even rarer is the phenomenon of one cancer metastasizing to another. Here, we present a case of mammary carcinoma and renal cell carcinoma diagnosed concurrently yet presenting as a cancer-to-cancer metastasis. Methods/Case Report A 79-year-old woman, with a 2-week duration of apnea and cough, was found to have right pleural effusion and underwent thoracocentesis. Cytological examination of the fluid revealed malignant cells suggestive of adenocarcinoma. CT abdomen and chest revealed a 1.6 cm right breast nodule, 4.4 cm right axillary mass and right renal lesions measuring 3.0 and 1.6 cm. Core biopsy of the renal lesion showed two populations of cells. One population exhibited moderate cytoplasm and enlarged nuclei displaying anisonucleosis and hyperchromasia arranged singly as well as in sheets and clusters. These cells stained positive for GATA 3, ER, mammaglobin and CK7. Intermixed, were the second population of cells with clear cytoplasm and low nuclear grade forming sheets and replacing renal tissue. These cells were positive for CA9, CD10 and PAX 8 but negative for P40. Based on these findings a diagnosis of low-grade renal carcinoma of clear cell type with a metastatic carcinoma of mammary origin was established. Results (if a Case Study enter NA) NA Conclusion Renal cell carcinoma and breast carcinoma are known to increase the occurrence of each other. When breast and renal lesions are identified concurrently, the possibility of breast metastasis should be strongly considered. However, the concurrent appearance of renal cell carcinoma harboring metastatic breast cancer is extremely rare.This contributes valuable insights into the complex interplay between different cancer types. Understanding these rare phenomena can aid in refining diagnostic approaches and treatment strategies.

Breast Metastasis From Sigmoid Adenocarcinoma Revealed by FDG PET/CT.

Breast metastasis from sigmoid carcinoma is rare. A 32-year-old woman, who had a history of sigmoid carcinoma, was found a hypermetabolic soft tissue mass in the left breast and a lymph node with moderate uptake on FDG PET/CT. Final pathology supported that the breast mass and lymph node were both metastases from the sigmoid carcinoma.

Uptake of germline genetic testing in patients with advanced breast, ovarian, pancreatic, or prostate cancer.

19 Background: With FDA approval of PARP inhibitors for treatment of BRCA1/2 -associated advanced breast, ovarian, pancreatic, and prostate cancer, National Comprehensive Cancer Network guidelines for germline genetic testing (GGT) have expanded for patients with these tumor types since 2019. We aimed to analyze factors associated with GGT uptake in these patient populations. Methods: We conducted a retrospective cohort study among patients diagnosed with metastatic breast and prostate cancer and all stages of ovarian and pancreatic cancer in 2020-2023 at Columbia University Irving Medical Center in New York City. We extracted data from the electronic medical record on demographics (age at diagnosis, sex, race/ethnicity, Jewish ancestry, marital status) and clinical characteristics (tumor type, year of diagnosis, family history of cancer, receipt of somatic testing, genetic counseling, targeted therapy). The primary outcome was receipt of GGT. Descriptive statistics were generated and multivariable logistic regression analyses were used to estimate the association between demographic/clinical factors and GGT uptake. Results: Among 884 evaluable patients, mean age was 67 years (SD, 14) and the study population included 45% Whites, 15% Blacks, 21% Hispanics, and 9% Asians/Others; 14% had Jewish ancestry. Only 16% were seen by a genetic counselor, 66% had undergone GGT, and 57% had somatic testing. After adjustment for confounders, younger age, Jewish ancestry, later year at diagnosis, and family history of breast or pancreatic cancer were significantly associated with GGT uptake. Patients with pancreatic or prostate cancer were about 60% less likely to undergo GGT compared to patients with ovarian cancer. Patients who had somatic testing were over 4.5-fold more likely to receive GGT. No significant differences were observed based upon sex or race/ethnicity. Among patients who underwent GGT, 20% were found to have a PV and over half of patients who received targeted therapy had PVs detected. Conclusions: We observed increasing use of oncologist-led GGT over time with over 65% of patients with advanced breast, ovarian, pancreatic, or prostate cancer undergoing testing, of which 20% had PVs detected. Given the evolution of targeted therapies and the potential downstream impact of known PVs for family members, under-utilization of GGT in patients with pancreatic and prostate cancer as well as older individuals should be addressed in future studies.

S610 Evaluating The Presentation and Clinical Management of Rare Secondary Esophageal Cancers From Breast Metastasis Origin: A Comprehensive Review of Case Reports

S610 Evaluating The Presentation and Clinical Management of Rare Secondary Esophageal Cancers From Breast Metastasis Origin: A Comprehensive Review of Case Reports

Hypoxic stabilization of RIPOR3 mRNA via METTL3-mediated m6A methylation drives breast cancer progression and metastasis.

Dysregulated N6-methyladenosine (m6A) modification has been associated with breast cancer pathogenesis. Hypoxia which characterizes solid tumors is known to reprogram the m6A epitranscriptome, but the underlying mechanisms of how this process contributes to breast cancer progression remain poorly understood. Through integrative analyses of m6A-RIP sequencing and RNA sequencing databases, we reveal a cluster of mRNAs with upregulated m6A methylation and expression under hypoxia, that are enriched by many oncogenic pathways, including PI3K-Akt signaling. Furthermore, we identify the mRNA, RIPOR3, as a target of METTL3-mediated m6A methylation in response to hypoxia. We find that m6A methylation stabilizes RIPOR3, increasing its protein expression in a METTL3 catalytic activity-dependent manner, and consequently driving breast tumor growth and metastasis. RIPOR3 is found to be overexpressed in breast cancer cell lines and tumor tissues from breast cancer patients, in whom elevated RIPOR3 is associated with a worse prognosis. Mechanistically, we show that RIPOR3 interacts with EGFR and is essential for the PI3K-Akt pathway activation. In conclusion, we identify RIPOR3 as a hypoxia-stabilized oncogenic driver via METTL3-mediated m6A methylation, thus provide a potential therapeutic target for breast cancer.

Assessing Breast Cancer through Tumor Microenvironment Mapping of Collagen and Other Biomolecule Spectral Fingerprints─A Review.

Breast cancer is a major challenge in the field of oncology, with around 2.3 million cases and around 670,000 deaths globally based on the GLOBOCAN 2022 data. Despite having advanced technologies, breast cancer remains the major type of cancer among women. This review highlights various collagen signatures and the role of different collagen types in breast tumor development, progression, and metastasis, along with the use of photoacoustic spectroscopy to offer insights into future cancer diagnostic applications without the need for surgery or other invasive techniques. Through mapping of the tumor microenvironment and spotlighting key components and their absorption wavelengths, we emphasize the need for extensive preclinical and clinical investigations.

The rare case of synchronous bilateral breast metastasis from a lung neuroendocrine tumor (small cell lung carcinoma): a case report and literature review

BackgroundBreast metastasis from small cell neuroendocrine carcinoma (SNEC) is very rare. In the present report, we describe a case of a female patient who was initially diagnosed with triple negative primary bilateral breast cancer, but during systemic examination, the diagnosis was bilateral breast metastasis from SNEC.Case presentationA 62-year-old woman with no history of smoking presented to the Department of General Medicine with left-sided chest pain, and computed tomography revealed masses in both breasts and left pleural thickening that was further confirmed by mammography and ultrasound of the breasts. A needle biopsy was performed, and triple negative primary bilateral breast cancer was diagnosed. Because progastrin-releasing peptide (ProGRP) 37,300 pg/ml (normal range, 0–81.0 pg/ml) and neuron-specific enolase 35.0 ng/ml (normal range, 0–16.3 ng/ml) levels were elevated, thoracoscopic biopsy was performed, and SNEC was diagnosed. Pathological examinations showed that the bilateral breast masses were also positive for immunohistochemical staining of chromogranin A, synaptophysin, and CD56, leading to a diagnosis of bilateral breast metastasis of neuroendocrine tumor.ConclusionAlthough very rare, the possibility of breast metastasis should be considered when malignancy is suspected in other organs.

Bilateral breast metastases from anaplastic lymphoma kinase-positive lung cancer in a male: a case report

BackgroundDistant metastases from lung cancer are commonly found in the brain, bone, and liver. Metastases to the breast from non-mammary malignancies are extremely rare, and their clinical presentations remain unclear.Case presentationWe herein report a case of bilateral breast metastases from anaplastic lymphoma kinase-positive advanced lung cancer in a 51-year-old Japanese male patient. During the course of systemic treatment for advanced lung cancer, computed tomography revealed bilateral breast enlargement without contrast enhancement, a finding consistent with gynecomastia. While other metastatic lesions responded to chemotherapy, both breast masses grew vertically like nodules. The breast masses were immunohistochemically diagnosed as metastases from lung cancer and were removed surgically. Simultaneous bilateral breast metastases from malignancies of other organs, like ones in this case, have rarely been described.ConclusionsIt is important to keep in mind that breast metastases from nonmammary malignancies are a possible explanation for unusual breast findings in a patient with a history of malignancies.