Hormone Receptor Status Research Articles

Mammographic parameters as predictors of molecular subtype of breast cancer: a prospective analysis

BackgroundThe prevalence of breast cancer is increasing globally and its early detection is the need of hour for giving the patient a long disease-free meaningful life. The latest management regimes depend upon the biological behavior of the breast cancer that itself relies upon expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her 2) neu status for its molecular subtyping.AimTo determine the predictive value of mammographic parameters in identifying the estrogen and progesterone hormone receptor status, human epidermal growth factor receptor 2 (Her 2) neu expression and molecular subtypes of breast cancer.MethodsA prospective observational study was conducted from January 2021 to September 2022 in a tertiary care institute. The study enrolled 51 females with histopathologically proven invasive breast carcinoma. The patients underwent digital mammography followed by tissue biopsy. Mammographic parameters were based on Breast Imaging-Reporting and Data System (BI-RADS) imaging features. The molecular subtypes of breast cancer were grouped into four subtypes based on St. Gallen International Expert Consensus Panel 2013. The mammographic features were then statistically correlated with molecular subtypes of breast cancer.ResultsLuminal type A was the most common molecular subtype in our study [ 17 (33.33%)] followed by triple negative type [10(19.61%)]. Tumors with non-circumscribed margins were predicted to be Luminal A or Luminal B subtype (p value < 0.02). Tumor with microcalcification was strongly predicted to be Her 2 subtype with a statistically significant association (p value < 0.001). Circumscribed tumors with absence of microcalcification were predicted to be triple-negative type of breast cancer.ConclusionsKey features in mammography were significantly associated with breast cancer molecular subtypes. Knowledge of such correlations could help clinicians stratify breast cancer patients according to their likely molecular subtypes, potentially enabling earlier, more effective treatment or aiding in therapeutic decisions in countries where immunohistochemical (IHC) hormone receptor and Her 2 testing is not readily available.

Standardization and advancements efforts in breast diffusion-weighted imaging.

Recent advancements in breast magnetic resonance imaging (MRI) have significantly enhanced breast cancer detection and characterization. Breast MRI offers superior sensitivity, particularly valuable for high-risk screening and assessing disease extent. Abbreviated protocols have emerged, providing efficient cancer detection while reducing scan time and cost. Diffusion-weighted imaging (DWI), a non-contrast technique, has shown promise in differentiating malignant from benign lesions. It offers shorter scanning times and eliminates contrast agent risks. Apparent diffusion coefficient (ADC) values provide quantitative measures for lesion characterization, potentially reducing unnecessary biopsies. Studies have revealed some correlations between ADC values and hormone receptor status in breast cancers, although substantial variability exists among studies. However, standardization remains challenging. Initiatives such as European Society of Breast Imaging (EUSOBI), Diffusion-Weighted Imaging Screening Trial (DWIST), Quantitative Imaging Biomarkers Alliance (QIBA) have proposed guidelines to ensure consistency in imaging protocols and equipment specifications, addressing variability in ADC measurements across different sites and vendors. Advanced techniques like Intravoxel incoherent motion (IVIM) and non-Gaussian DWI offer insights into tissue microvasculature and microstructure. Despite ongoing challenges, the integration of these advanced MRI techniques shows great promise for improving breast cancer diagnosis, characterization, and treatment planning. Continued research and standardization efforts are crucial for maximizing the potential of breast DWI in enhancing patient care and outcomes.

Predictive Factors of Antibody–Drug Conjugate Treatment in Metastatic Breast Cancer: A Narrative Review

Antibody–drug conjugates (ADCs) have revolutionized the treatment landscape for metastatic breast cancer, offering targeted delivery of cytotoxic agents with improved efficacy and tolerability compared to conventional chemotherapy. This narrative review explores key predictive factors influencing the efficacy of ADCs, focusing on HER2-targeted therapies, such as trastuzumab emtansine and trastuzumab deruxtecan, as well as sacituzumab govitecan for triple-negative breast cancer. HER2 expression, TROP-2 levels, hormone receptor status, and the tumor microenvironment emerge as critical biomarkers for patient selection and therapeutic outcomes. Additionally, we discuss resistance mechanisms, such as antigen loss, impaired drug internalization, and the role of circulating tumor DNA in predicting ADC response. Finally, future perspectives on the sequential use of ADCs and potential combination therapies are highlighted, along with emerging agents targeting alternative antigens like HER3 and LIV-1. Overall, identifying predictive biomarkers and overcoming resistance mechanisms are essential for optimizing the use of ADCs in metastatic breast cancer, thereby improving patient outcomes.

Clinicopathological characteristics of Japanese patients with breast cancer and MET exon 14 skipping alterations.

In non-small cell lung cancer, alterations in mesenchymal-epithelial transition (MET) have been recognized as novel therapeutic targets. In particular, the MET exon 14 skipping mutation (METex14s) is a rare oncogenic driver. Targeted therapy with MET tyrosine kinase inhibitors has recently been approved for this mutation. However, c-MET expression and METex14s frequency and their clinicopathological effects in Japanese patients with breast cancer (BC) remain unknown. Tissue microarray-based immunohistochemistry (IHC) was performed to measure c-MET expression in 930 patients with BC (808 with invasive and 122 with noninvasive BC). Reverse transcription polymerase chain reaction was performed to analyse METex14s in patients exhibiting c-MET expression. Clinicopathological characteristics, including patient prognosis based on c-MET expression and METex14s, were elucidated. IHC staining revealed c-MET expression in 91/930 (9.7%) patients. Notably, IHC expression was frequently observed in apocrine carcinomas (11/26 cases). Among the c-MET IHC-positive cases, METex14s frequency was 25.9% (14/54 cases) in invasive BC and 54.1% (20/37 cases) in noninvasive BC. Furthermore, 4/11 informative noninvasive and invasive BC cases with apocrine differentiation carried METex14s. The nuclear grade was significantly higher in the METex14s-positive group among invasive BC with c-met IHC expression. Furthermore, patients' age and negative rate for PgR IHC was significantly lower in the METex14s-positive group among noninvasive BC. Regarding the factors associated with patient outcomes, both c-MET IHC staining and METex14s expression did not affect survival, regardless of the hormone receptor status. High c-MET expression and METex14s are common in apocrine carcinoma.

Pexidartinib and standard neoadjuvant therapy in the adaptively randomized I-SPY2 trial for early breast cancer.

We investigated the small-molecule receptor tyrosine kinase-inhibitor of colony-stimulating factor-1 receptor pexidartinib in the stage II/III breast cancer in the I-SPY2 platform trial. I-SPY2 is an adaptive platform trial that features multiple arms of experimental agents administered on a background of standard neoadjuvant therapy with paclitaxel and adriamycin/cyclophosphamide, followed by definitive surgery. The adaptive randomization engine preferentially assigns patients based upon cumulative performance of each agent in a given breast cancer subtype based on hormone receptor and HER2 receptor status. The study endpoint is pathologic complete response. A total of 9 participants were randomized to receive pexidartinib with neoadjuvant paclitaxel before enrollment was halted due to a serious adverse event of vanishing bile duct syndrome. No participants received a full course of the study drug. Although there remains interest in agents targeting CSF-1, hepatic toxicity appears to be a limiting factor for their use in early breast cancer. NCT01042379 ( www. gov/ct2/show/NCT01042379 ).

Small intestinal metastasis from primary breast cancer: a case report and review of literature

Small intestinal metastasis from primary breast cancer remains a rare clinical occurrence. Despite extensive research into its clinicopathological features and treatment options, the specific pathogenesis and optimal management strategies remain incompletely understood. This case report presents a patient with breast cancer that metastasized to the small intestine. The primary breast tumor was diagnosed as classic invasive lobular carcinoma. Subsequent surgical intervention successfully addressed the intestinal obstruction and confirmed the metastatic origin of the small intestinal tumor. Interestingly, the metastatic lesions exhibited features suggestive of pleomorphic lobular carcinoma. A PET-CT scan was performed to evaluate the distant metastasis status of this patient. Notably, hormonal receptor status shifted from positive to negative, while HER2 expression changed from negative to low between the primary tumor and metastatic lesions. The presence of an undiagnosed pleomorphic component in the primary tumor might explain the disease’s progressive nature. In this case, systemic treatment with trastuzumab deruxtecan yielded favorable therapeutic outcomes. Overall, our findings suggest that re-evaluation of receptor status in breast cancer metastases is crucial for tailoring treatment strategies. Furthermore, a combination of palliative resection of small intestinal metastases and targeted therapy for HER2-low breast cancer may potentially improve survival.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma.

Breast cancer remains a significant cause of mortality globally, necessitating effective treatment strategies. Neoadjuvant chemotherapy (NAC) is widely employed to minimize tumor burden and prevent local spread, with treatment efficacy varying based on molecular subtypes. Despite advancements, resistance to conventional therapies persists, prompting the exploration of alternative approaches, including immune cell therapy. Tumor-infiltrating lymphocytes (TILs) have emerged as immunological biomarkers in breast cancer, exhibiting associations with molecular subtypes and treatment response. This retrospective study assessed the clinico-pathological relationship between stromal TILs and AR expression across molecular subtypes of invasive breast carcinoma in an Indian cohort. Thirty-seven patients receiving NAC followed by modified radical mastectomy were analyzed for TILs and molecular subtyping. Immunohistochemistry was used to determine hormone receptor status and AR expression. A higher AR positivity was observed in hormone receptor-positive/Her2neu-negative and hormone receptor-positive/Her2neu-positive tumors compared to triple-negative breast cancers (TNBCs). Significant associations were observed between AR expression and tumor grade, but not with age or Her2neu status. Although no significant correlation was found between AR and complete response to NAC, a weak negative correlation between AR and TILs was noted. Notably, TNBCs with negative AR and Ki67 index exhibited poorer responses to NAC, emphasizing the need for adjuvant therapy. These findings underscore the complex interplay between AR, TILs, and treatment response in breast cancer, highlighting the potential of personalized therapeutic approaches. Further research is warranted to elucidate the prognostic significance of AR and its implications for tailored treatment strategies in breast cancer management.

Radiology–pathology correlation of hormonal subtypes of breast cancer based on mammography, ultrasound, and PET imaging

BackgroundBreast cancer is one of the most common cancers among the female population globally and a major cause of death due to cancers among women. It has been classified into histopathological, hormonal, and molecular subtypes based on hormone receptor status. Their management involves a multidisciplinary approach depending on these subtypes, TNM staging, tumour size, and site. The purpose of this study was to assess the correlation between ultrasound and mammography characteristics and the maximum standardized uptake value on PET with hormonal subtypes of breast cancer.MethodsIt was a retrospective study from a single-centre data available for 8 months. In this study, 5 hormonal subtypes were considered; Luminal A, Luminal B, Luminal HER2-positive subtype, HER2-enriched subtype, and triple-negative subtype. The morphology of the lesions analysed on mammography and sonography and the SUV max value on PET were considered for analyses. The prediction performance of these features for the hormonal subtypes of breast cancers was then analysed.ResultsLuminal A and B subtypes of breast cancer had indistinct margins with posterior acoustic shadowing on ultrasound. Triple-negative subtypes were well-circumscribed lesions with posterior acoustic enhancement on ultrasound. HER2-positive lesions characteristically had pleomorphic microcalcifications with mixed posterior acoustic features on mammography. On PET, HER2-enriched cases had the highest SUV, and the Luminal A subtype had the lowest SUV.ConclusionAccording to our observations, there are certain typical morphological imaging characteristics for each hormonal subtype of breast cancer. These imaging modalities may help radiologists and clinicians in stratifying their patients for prognostication and better management.

Survival trends of patients with metaplastic breast carcinoma with different hormone receptor statuses: a SEER-based retrospective cohort study

BackgroundMetaplastic breast carcinoma (MpBC) is a rare histological subtype of breast cancer, and its prognosis is relatively poor. The survival trend of MpBC with different hormone receptor statuses has remained unclear over the past two decades.MethodsMpBC patient data were collected from the Surveillance, Epidemiology, and End Results database from 2000 to 2019. Patients were divided into two groups according to their hormone receptor status (negative and positive). The survival probabilities were calculated via Kaplan‒Meier curves. Logistic regression analysis was used to obtain odds ratios for treatment and demographic characteristics. Multivariate Cox regression was used to identify prognostic factors.ResultsA total of 3,076 patients were enrolled, and a significant improvement in survival was observed over the last 10 years. For HR-negative MpBC patients, both overall survival and breast cancer-specific survival improved, whereas no survival improvement was observed for HR-positive patients. Compared with those in the time period from 2000 to 2009, the proportion of negative nodes and the likelihood of receiving chemotherapy increased for HR-negative patients from 2010 to 2019. In the HR-negative subgroup, the survival of Whites improved significantly, whereas the survival of Blacks improved in the HR-positive subgroup.ConclusionsThe survival of HR-negative MpBC patients has improved significantly in the past 20 years, which may be related to early diagnosis, increased adjuvant therapy and medical development, but no trend towards improvement has been observed in HR-positive patients. Racial disparities in different HR statuses also need to be addressed.

Alcoholic beverage consumption and female breast cancer risk:A systematic review and meta-analysis of prospective cohort studies.

Alcohol consumption is an established cause of female breast cancer. This systematic review examines in detail the association between alcohol and female breast cancer overall and among the described subgroups, using all of the evidence to date. A systematic review of PubMed and Embase was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included articles published up to November 15, 2023. Meta-analyses and regressions were performed for alcohol consumption of less than 1 standard drink (10 g of ethanol) per day and for a range of alcohol consumption categories in relation to breast cancer. Analyses by menopausal status, hormone receptor status, human epidermal growth factor receptor 2 status, and molecular subtype were performed. The search yielded 5645 publications, of which 23 publications of individual and pooled studies examined the association between overall alcohol consumption and breast cancer incidence. The meta-regression showed a positive association; relative risks (RR) of breast cancer were 1.05 (95% CI: 1.04, 1.06), 1.10 (95% CI: 1.08, 1.12), 1.18 (95% CI: 1.15, 1.21), and 1.22 (95% CI: 1.19, 1.25) for 0.5, 1, 2, and 3 standard drinks per day compared with nondrinking, respectively. A meta-analysis of nine studies indicated that for consumption of less than one standard drink per day, the RR estimate of breast cancer was 1.04 (95% CI: 1.01, 1.07) compared with nondrinking. Consumption of an additional 1 standard drink per day was associated with a higher risk of premenopausal (RR: 1.03 (95% CI: 1.01, 1.06)) and postmenopausal (RR: 1.10 (95% CI: 1.08, 1.12)) breast cancer. Alcohol consumption increases female breast cancer risk, even for women who consume one drink per day. Furthermore, alcohol consumption is associated with both pre- and postmenopausal breast cancer risk. These findings support evidence-based cancer prevention guidelines to reduce alcohol-related risks.

Patterns of subsequent cancer incidence over time in patients with breast cancer.

Breast cancer survivors face a higher risk of subsequent primary cancers. This study investigated the patterns of subsequent cancer risk according to time since breast cancer diagnosis. Using data from the Surveillance, Epidemiology, and End Results program (2000-2018), we identified a cohort of 771,681 breast cancer survivors. Standard incidence ratios (SIR) were calculated by comparing the observed to the expected number of subsequent cancers over different follow-up periods since breast cancer diagnosis. Analyses were conducted for multiple cancer types, stratified by hormone receptor (HR) status and treatment of the first breast cancer, age, and race/ethnicity. Survivors experienced a 16% increased risk of subsequent cancer with the SIR continuing to increase with longer follow-up (SIR=1.04, 1.22, and 1.31 for 12-59, 60-119, and ≥120 months). This trend was driven primarily by a subsequent breast cancer, particularly among women <50 years, those with initial HR-negative cancer, and racial/ethnic minorities. The patterns of subsequent non-breast cancer risk varied by type. An early-onset and sustained increased risk was observed for subsequent leukemia, thyroid, soft tissue, melanoma, pancreas, and uterine cancer. A delayed increased risk was observed for subsequent esophagus, ovarian, oral cavity/pharynx, and lung cancer, while for small intestine, stomach, kidney, and colorectal cancer there was a decrease after an initial increased risk. Patterns in subsequent cancer risk since breast cancer diagnosis differ by cancer type and characteristics of the first breast cancer. These findings can inform etiology and tailored approaches to screening and prevention of subsequent cancers.

Association of Level III Axillary Lymph Node Positivity with Clinicopathological Characteristics in Breast Cancer

Management of breast cancer has gradually shifted from era of radical surgery to present days of multi-modality management and conservatism. While complete axillary dissection is common for node-positive cases, less invasive approaches like sentinel node biopsy are often sufficient for clinically node-negative cases. However, these findings may not apply to all populations, particularly in India where advanced disease presentation is common. The objective of this study is to assess Level III Axillary Lymph Node Positivity with clinicopathological characteristics in Breast cancer. This was a hospital based retrospective observational study on breast cancer patients conducted in single institute from 2016 to 2022. A total of 70 patients with operable breast cancers, who underwent primary tumour resection and complete axillary lymph node dissection, including level III were included in the study. Patients with inoperable and metastatic disease were excluded. Final histopathological examination data was collected and analysed. Most patients (92.9%) underwent Modified Radical Mastectomy, with Infiltrating Ductal Carcinoma (IDC) being the most common histology (90%). Factors significantly associated with level III lymph node positivity included tumour size &gt;4.5cm, nuclear grade III, pathological N3 stage and extra nodal extension. The study found no significant correlation with other factors like age, tumour laterality, location, hormone receptor status, HER2 status, or LVSI. These findings may help predict level III lymph node involvement in breast cancer patients. All these predictive factors should be considered during the axillary dissection.

Case series of pure mucinous breast carcinoma: A rare histopathological subtype

Pure mucinous breast carcinoma (PMBC) is even rarer and accounts for about 2% of all primary breast carcinoma. It is composed entirely of tumour cells with abundant extracellular mucin and without admixing of infiltrating ductal carcinoma. We studied a total of ten cases of Pure Mucinous Breast Carcinoma. Here we describes each case of demographic features and histopathological features of PMBC. The results of immunohistochemistry of Estrogen receptor (ER), Progesterone receptor (PR), Human epidermal growth factor receptor 2(HER-2neu) were also noted in this case series. All the cases were female and above 50 years of age. Out of 10 cases, 6 cases have the tumour’s location on the left side of the breast and 4 cases have the tumour’s location on the right side of the breast. All the cases belong to the lower grading and staging of the tumour. Only one case had positive lymph node status.Hormone receptor status of all the cases has ER &amp; PR positive expression, HER-2neu negative expression and low Ki 67 labelling index. To conclude, PMBC was associated with lower-grade tumours, lower-stage, infrequent lymph node metastasis and luminal type A hormonal receptor status. These favourable findings suggest that PMBC has a better prognosis and may give a better response to hormonal therapy.

Abstract B074: Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care

Abstract Objective: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. Patients and methods: Formalin-fixed paraffin- embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. Results: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. Conclusion: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary-level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context. Citation Format: Zelalem Desalegn Woldesonbet, Meron Yohannes, Martin Porsch, Kathrin Stückrath, Endale Anberber, Pablo Santos, Marcus Bauer, Adamu Addissie, Yonas Bekuretsion, Mathewos Assefa, Yasin Worku, Lesley Taylor, Tamrat Abebe, Eva J Kantelhardt, Martina Vetter. Intrinsic subtypes in Ethiopian breast cancer patients: Implications for better care [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B074.

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption through a rise in pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and RANKL, which promote osteoclastogenesis. In the classic genomic pathway, estrogen binds to estrogen receptors in the cytoplasm, forming a complex that migrates to the nucleus and binds to estrogen response elements on DNA, regulating gene transcription. Androgens can be defined as high-affinity ligands for the androgen receptor; their combination can serve as a ligand-inducible transcription factor. Hormone replacement therapy has shown promise but comes with associated risks and side effects. In contrast, the non-genomic pathway involves rapid signaling cascades initiated at the cell membrane, influencing cellular functions without directly altering gene expression. Therefore, the ligand-independent actions and rapid signaling pathways of estrogen and androgen receptors can be harnessed to develop new drugs that provide bone protection without the side effects of traditional hormone therapies. To manage primary osteoporosis, other pharmacological treatments (bisphosphonates, teriparatide, RANKL inhibitors, sclerostin inhibitors, SERMs, and calcitonin salmon) can ameliorate osteoporosis and improve BMD via actions on different pathways. Non-pharmacological treatments include nutritional support and exercise, as well as the dietary intake of antioxidants and natural products. The current study reviews the processes of bone remodeling, hormone actions, hormone receptor status, and therapeutic targets of primary osteoporosis. However, many detailed cellular and molecular mechanisms underlying primary osteoporosis seem complicated and unexplored and warrant further investigation.

Predicting ipsilateral supraclavicular lymph node pathological complete response: nomogram based on the inflammatory markers.

The prediction of ISLN pCR after neoadjuvant chemotherapy (NAC) based on inflammatory markers and its prognostic value have rarely been investigated. Patients diagnosed with ISLN-involved breast cancer who received NAC in West China Hospital between September 2009 and December 2020 were enrolled in the derivation cohort for model construction and survival analysis, and patients with the same criteria between January 2021 and July 2024 were involved in validation cohort for external validation. After randomly dividing patients into training and testing groups at 7:3 ratio, a nomogram predicting ISLN pCR was constructed based on logistic regression in training group. Internal validation was performed in the testing group and external validation was performed in the independent validation cohort. The ROC curves were applied to validate the accuracy of the model. Survival analysis was performed using Kaplan-Meier plots. A total of 120 eligible patients were involved in the derivation cohort to establish the nomogram (84 patients in training group and 36 patients in testing group), and 45 patients were involved in the independent validation cohort for external validation of the nomogram. Pretreatment NLR and hormone receptor (HR) status, as well as preoperative SII, CEA, CA15-3 and anti-HER2 therapy were included in the nomogram predicting ISLN pCR. The AUC were 0.906 (95% CI 0.837-0.975, P<0.001), 0.888 (95% CI 0.751-1.000, P<0.001) and 0.828 (95% CI 0.703-0.953, P< 0.001) in training, testing groups and the validation cohort respectively. ISLN pCR was significantly associated with better prognosis (all P<0.05). Inflammatory factors combined with tumor makers, hormone receptor status and anti-HER2 therapy could predict ISLN pCR effectively, which was significantly associated with improved survival outcomes.

Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2-Overexpressing Breast Cancers.

Human epidermal growth factor receptor 2 (HER2) overexpression (HER2+) is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Response differences to neoadjuvant anti-HER2 therapy (NT) in IHC3+ versus IHC2+/ISH+ breast cancer patients are poorly characterized. We explored whether pathologic complete response (pCR) varies by HER2 IHC status. Patients with stage I-III HER2+ breast cancer undergoing NT and surgery between 2013 and 2020 were identified from the National Cancer Database and stratified by IHC status. Breast and nodal pCR were analyzed. Of 40,711 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor (HR)-negative (33 vs. 21%), have cT3/4 tumors (24 vs. 21%), and be cN+ (52 vs. 47%; all p < 0.0001). Breast conservation rates were similar (each 43%, p = 0.32), although IHC3+ axillary lymph node dissection rates were lower (41 vs. 45%, p < 0.0001). Among all patients, breast pCR was 49%, while nodal pCR was 64%. Compared with IHC2+/ISH+, IHC3+ had higher unadjusted breast (54 vs. 22%, p < 0.0001) and nodal (69 vs. 37%, p < 0.0001) pCR rates. When stratified by HR status, pCR was lower for HR+ disease but remained higher among IHC3+ patients. Analysis of T1cN0 primaries mirrored these trends. In multivariable analysis, IHC3+ remained an independent predictor of breast (odds ratio [OR] 3.91, confidence interval [CI] 3.65-4.19, p < 0.0001) and nodal (OR 3.40, CI 3.12-3.71, p < 0.0001) pCR. HER2 IHC status predicts pCR and may help select breast cancer patients who derive the greatest benefit from NT. These findings provide further evidence that revision of HER2 classification may improve clinical management.

A bidirectional Mendelian randomization analysis of the causal relationship between inflammatory bowel disease and breast cancer based on estrogen receptor status

The incidence of patients diagnosed with either breast cancer (BC) or inflammatory bowel disease (IBD) is increasing each year. IBD has been shown to be strongly associated with the development of a variety of solid tumors, but the relationship with breast cancer is not yet definitive. We explored the causative relationship between IBD and BC using a Mendelian randomization (MR) strategy. MR-Egger regression, weighted median (WM), simple median (SM), maximum likelihood (ML), and inverse variance weighting (IVW) methods were among the analytical techniques used in this work. The examination of heterogeneity was conducted by the use of Cochran's Q test and Rucker's Q test. The sensitivity analysis in this study used the IVW and MR-Egger methodologies. The results of our investigation suggested that IBD had a beneficial impact on estrogen receptor-negative (ER-) breast cancer (odds ratio (OR) = 0.92, P = 0.02). The study did not find a significant association between IBD and the risk of developing overall breast cancer (OR = 0.99, P = 0.60), as well as estrogen receptor-positive (ER+) breast cancer (OR = 1.02, P = 0.60) specifically. In addition, our study findings indicated that there was a detrimental association between ER+ breast cancer and IBD as determined using reverse MR analysis (OR = 1.07, P = 0.04). Furthermore, this analysis failed to observe any significant association between overall breast cancer (OR = 1.07, P = 0.07) or ER- breast cancer (OR = 0.99, P = 0.89) and IBD. Our bidirectional MR study yielded a correlation between IBD and some specific hormone receptor status of BC.

Pathomorphological examination of specimen after vacuum-assisted biopsy in patients with breast cancer after neoadjuvant systemic therapy

Introduction. Vacuum-assisted biopsy (VAB) of the tumor bed in the breast has shown promising results as a minimally invasive method for determining pCR. A significant disadvantage of VAB is the fragmentation of the obtained material and the lack of methods for determining generally accepted predictive and prognostic factors.The objective was to provide a description of the accumulated experience of histological examination of specimens obtained using VAB in patients with breast cancer after neoadjuvant systemic therapy.Methods and materials. A single-center, prospective, non-randomized study included patients with unifocal breast cancer (cT1–2N0–1M0). Patients who achieved a complete clinical response (cCR) underwent VAB. Based on the results of histological examination, patients without signs of residual tumor (pCR, ypT0N0) did not undergo further surgical intervention. When residual tumor cells (ypTisN0-1, ypT1-2N0-1) were detected, standard breast surgery was performed.Results. 35 patients with a mean age of 48.3 (31–67) years were included in the analysis. The examination of VAB samples showed that 11 (31.4 %) patients had a residual tumor, and in 24 (68.6 %) patients, no tumor cells were detected (ypT0N0). According to the Miller-Payne system, 28 patients had a complete pathological response, which corresponds to Miller-Payne=5 and pathological stage ypT0/ypTis (24 patients ypT0N0, 3 patients ypTisN0 and 1 patient ypT0N1). In 3 patients with residual invasive tumor, the tumor response according to the Miller-Payne scale corresponded to grade 3. There was a statistically significant correlation between presence of residual tumor cells in the outer counter after VAB and presence of residual tumor cells in the postoperative histology after standard surgery (Х2 p=0.01, Fisher exact test p=0.048). In addition, there was a statistically significant correlation between hormone receptor status and the degree of tumor response when evaluated using the Pearson criterion (p=0.046). We observed the smallest discordance between the data of the control examination and the data of the histological conclusion when interpreting the results of mammolymphoscintigraphy (25 %) and if 3 out of 3 studies described a complete clinical regression (16.7%).Conclusions. The method used to evaluate histological material allows to obtain predictive and prognostic information necessary to clarify further treatment tactics in accordance with modern standards. It is necessary to conduct more largescale studies in this area to answer the question if this method can be used in routine clinical practice.

HLA-I and breast cancer prognosis: A systematic review and meta-analysis

BackgroundBreast cancer (BC) is a significant global health issue, accounting for 1 in 8 cancer diagnoses worldwide. HLA class I molecules are typically expressed on the cell surface, but cancer cells can develop mechanisms to evade recognition by CTLs, including the downregulation of HLA class I expression. In this context, we aimed to conduct a systematic review and meta-analysis to clarify the role of HLA class I expression in clinical outcomes for patients with BC. MethodsA comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases. Effect sizes, along with I2 and Tau2 statistics, were used to assess heterogeneity through a DerSimonian and Laird random-effects model. Statistical analyses were performed using R statistical software, version 4.2.3. ResultsAmong the 8 included studies, most of the analyzed samples consisted of ductal carcinoma cases (1588, 86.39 %), from the luminal (A or B) intrinsic subtype (1865, 69.07 %), with no lymph node metastasis (2658, 57.24 %), no HER2 overexpression (2594, 67.46 %), negative Ki67 status (1721, 71.26 %), and positive hormone receptor status (4732, 64.05 %). The analysis revealed a significant reduction in disease-free survival (HR 0.57; 95 % CI 0.34 to 0.95; p = 0.034; I2 = 84 %) in the group with low HLA-I expression. However, no significant difference was found between the groups with high and low HLA-I expression regarding overall survival (HR 0.77; 95 % CI 0.28 to 2.14; p = 0.62; I2 = 86 %). ConclusionsThis systematic review and meta-analysis demonstrated that HLA class I expression is associated with a significant improvement in disease-free survival, though no significant effect on overall survival was observed.