Estrogen Receptor Status Research Articles

Genetic evidence supporting the causal role of 25-hydroxyvitamin D levels in the prognosis of ER- breast cancer: A Mendelian randomization study.

This study aims to investigate the connection between 25-hydroxyvitamin D (25(OH)D) levels and the prognosis of breast cancer with various estrogen receptor (ER) statuses. The summary statistics of 25(OH)D levels was obtained from a GWAS of 441,291 individuals and the information of breast cancer was collected from the Breast Cancer Association Consortium. We analyzed the causal association between 25(OH)D levels and breast cancer prognosis using a number of approaches, including inverse variance weighting (IVW). The heterogeneity test was performed using Cochran Q test. IVW, Mendelian randomization (MR)-Egger, and MR Pleiotropy RESidual Sum and Outlier methods were used for sensitivity analysis. In addition, a multivariate MR adjusted for total triglycerides, total cholesterol, and body mass index was used for further analysis. Two-sample MR results showed that 25(OH)D levels were not associated with prognosis in overall breast cancer (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.73-1.19, IVW exam) and estrogen receptor positive (ER+) breast cancers (OR = 1.12, 95% CI = 0.77-1.63, IVW exam) and were protective associated with prognosis in estrogen receptor negative (ER-) breast cancers (OR = 0.55, 95% CI = 0.34-0.87, IVW exam). Sensitivity analysis did not observe the presence of heterogeneity and horizontal pleiotropy. In multivariate MR analysis, after adjusting for total triglycerides, total cholesterol, and body mass index, the correlation between the protective relationship between 25(OH)D levels and the prognosis for ER- breast cancer remained and became increasingly significant (OR = 0.51, 95% CI = 0.31-0.83, P = .007). This study demonstrated a protective relationship between 25(OH)D levels and the prognosis of ER- breast cancer, but there was no connection between 25(OH)D levels and the prognosis of ER+ breast cancer.

Mammographic density and breast cancer risk among Black American women.

High mammographic density is a well-established risk factor for breast cancer; however, data from Black women are limited. It is largely unknown how mammographic density is associated with breast cancer subtypes among Black women. We examined the association between percent mammographic density (PMD) and breast cancer risk among participants in the Black Women's Health Study. Digital screening mammograms were available for 363 cases and 5541 non-cases. Cumulus software was used to assess PMD. We used inverse probability of sampling weights and Cox proportional hazards models, adjusted for age and body mass index, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) overall and by age at mammography and estrogen receptor (ER) status of the breast tumors. Multivariable models included additional breast cancer risk factors. Tests of statistical significance were 2-sided. In simple models, women in the highest quartile of PMD had 53% increased odds of breast cancer compared to those in the lowest quartile (HR 1.53; 95% CI: 1.11, 2.11). HRs were 1.37 (95% CI: 0.83, 2.24) among women <55 years of age and 1.68 (95% CI: 1.10, 2.56) among women aged ≥55 years. HRs were 1.49 (95% CI: 1.02, 2.16) for ER+ cancer and 1.45 (95% CI: 0.73, 2.87) for ER- cancer. Associations were largely unchanged in multivariable models. In this study of U.S. Black women, higher PMD was associated with ER+ and ER- breast cancer risk. Findings from this study reinforce the importance of breast density as a risk factor for breast cancer in Black women.

Reproductive Risk Factor Patterns in Caribbean Women With Breast Cancer Across 4 Generations

Breast cancer (BC) is commonly diagnosed among Caribbean women. Shifts in reproductive patterns modify the incidence of BC diagnosis and age at BC diagnosis in population-based studies; however, reproductive patterns in Caribbean women remain understudied. To describe the temporal trends in reproductive patterns and age at BC diagnosis in Caribbean-born women. A cross-sectional observational study-the Caribbean Women's Cancer Study-was conducted, with data on reproductive patterns known to affect BC risk collected in The Bahamas, Barbados, Cayman Islands, Dominica, Haiti, Jamaica, and Trinidad and Tobago. Participants were recruited prospectively. The sample included women born in Caribbean countries and diagnosed with invasive BC and/or ovarian cancer from June 1, 2010, to June 30, 2018, and was divided into 4 birth cohorts (born before 1950, 1950-1959, 1960-1969, and in or after 1970). Data were analyzed between August 1, 2023, and July 31, 2024. Receipt of a BC diagnosis and birth in a Caribbean country. Change in reproductive patterns between birth cohorts, including age at BC diagnosis, family history of cancer, age at first pregnancy, number of pregnancies, number of full-term pregnancies, number of siblings, age at menarche and menopause, estrogen receptor status, and germline pathogenic/likely pathogenic variants. Of 1015 participants diagnosed with BC and ovarian cancer, 995 women (mean [SD] age, 46.6 [10.8] years; 605 [81.8%] Afro-Caribbean, 98 [13.2%] East Indian, 22 [3.0%] White, and 12 [1.6%] >1 race) received a diagnosis of invasive BC. Comparison from older to younger birth cohorts (presented in the order of born before 1950, 1950-1959, 1960-1969 and in or after 1970) showed an increased proportion of women experiencing menarche at age 12 years or younger (33.0% vs 47.3% vs 45.5% vs 57.9%; P < .001), women with no pregnancies (6.8% vs 6.8% vs 10.5% vs 22.8%; P < .001), and nulliparous women (8.6% vs 9.2% vs 13.9% vs 27.6%; P < .001). Younger age at BC diagnosis was observed in women experiencing menarche at age 12 years or younger (mean [SD], 45.0 [10.5] years) vs 15 years or older (mean [SD], 49.1 [11.2] years) and in nulliparous women (mean [SD], 42.1 [11.2] years) vs 3 or more full-term pregnancies (mean [SD], 49.9 [10.6] years; P < .001). For every year of first pregnancy delay, women had a 4% increased chance of being diagnosed with estrogen receptor-positive tumors (odds ratio, 1.04; 95% CI, 1.01-1.08; P = .02). In this cross-sectional study, between each 10-year birth cohort, women diagnosed with BC had a lower age at menarche, number of pregnancies, and number of full-term pregnancies. These findings suggest that interventions targeting other BC risk factors need to be implemented.

Immunohistochemical Expression of Cyclin D1 in Invasive Breast Carcinoma

Objective: This study was conducted to determine the immunohistochemical expression of cyclin D1 in invasive breast carcinoma and its association with already established prognostic parameters like estrogen receptor (ER), progesterone receptor (PR), HER2/Neu, and Ki67 status. Study Design &amp; Setting: Cross sectional Observational. Department of Pathology, Armed Forces Institute of Pathology, Rawalpindi Methodology: The study included 350 cases of invasive breast cancer diagnosed between January 2023 and December 2023. Data collected included patient age, histological subtype, molecular subtypes, tumor size, and the presence of estrogen (ER) and progesterone (PR) receptors, as well as HER2/Neu and Ki67 status. Patients who had undergone chemotherapy, received radiation to the breasts, or experienced relapse were excluded from the study. Immunohistochemistry was conducted using a Cyclin D1 antibody to assess Cyclin D1 expression in tissue samples. The expression levels were categorized as negative, weak, moderate, strong staining in tumor cells. Data analysis was performed using SPSS 29.0, and statistical comparisons were made between Cyclin D1 staining and ER, PR, HER2/Neu, and Ki67 status. Results: Cyclin D1 moderate to strong staining was seen in 173/352 (49.14%) cases of invasive BC. Cyclin D1 expression was slightly statistically significantly associated with ER (x2 = 7.78, P value &lt;0.051) and Ki67 positivity (÷2 = 7.27, P value &lt;0.064). Conclusion: Cyclin D1 has the potential to serve as a prognostic marker. Incorporating it into the routine IHC workup for breast cancer could enhance patient management, especially with the development of new targeted therapies that inhibit the Cyclin D-CDK4/6 axis.

Interleukin-33 Levels are Up-Regulated in Women with Breast Cancer and Shown to be Associated with the Triple-Negative Type

Breast cancer (BC) is a diverse disease with heterogeneous subgroups in pathophysiology and behavior. Recent advances in biomarker-based therapy may help improve treatment options for BC. Thus, this study aimed to assess the role of interleukin (IL)-31 and IL-33 as biomarkers associated with BC risk. Serum concentrations of IL-31 and IL-33 were quantified in women with BC (n = 77), women with benign breast lesion (BBL; n = 51), and healthy women (n = 75), using enzyme-linked immunosorbent assay kits. Compared with BBL or healthy women, IL-33 concentrations were significantly greater in BC patients and were associated with a 1.33-fold increased risk of disease and had excellent prognostic value in BC (area under the curve = 0.89). In addition, IL-33 expression was linked to triple-negative BC, distant metastasis, Tumor-Node-Metastasis (TNM) stage, status of estrogen and progesterone receptors, and human epidermal growth factor receptor 2. IL-31 concentrations showed no significant differences between BC, BBL, and healthy women, but were greater in patients with distant metastasis and those who were negative for estrogen and progesterone receptors. In conclusion, IL-33 and to a lesser extent IL-31 can be used as biomarkers associated with BC risk and to identify patients with a poor prognosis especially those with triple-negative BC. Furthermore, understanding the connection between IL-33 and BC progression may aid in the development of safe and effective therapy.

The effect of total size, area, and volume of lesions in multifocal/multicentric breast cancers and unifocal breast cancers on survival: An observational study.

In this study, we aimed to investigate the prognostic effect of the classifications made according to the stage of the largest lesion diameter (T-max stage) and of the sum of the longest diameters of the lesions (T-sum stage), the largest area stage (A-max stage), the sum of the largest areas (A-sum stage), the highest volume stage (V-max stage), the sum of the highest volume (V-sum stage) on disease-free survival, and overall survival (OS) in multifocal/multicentric breast cancers (MMBCs) and unifocal breast cancers (UBCs). The study included a total of 769 patients either with MMBC (n = 128) or UBC (n = 641) who underwent surgery between 2006 and 2015. In the analysis, the median age of 769 patients was 53.0 (20.0-94.0) years, and 16.6% of these 769 patients were MMBC and 83.4% were UBC. In multivariate analysis, lymphovascular invasion (LVİ), estrogen receptor, and nodal status were common independent prognostic factors, whereas T-max stage [(HR: 1.17) (CI 95%: 1.03-1.33) (P = .018)] was a prognostic factor for OS. In multivariate analysis, the T-max stage is an independent risk factor for OS. Therefore, T-max should be continued to be used for measurement and T-stage should be used for classification in MMBCs/UBCs.

The Predictive Role of Mammography, Dynamic Contrast-Enhanced Breast Magnetic Resonance Imaging and Diffusion-Weighted Imaging in Hormone Receptor Status of Pure Ductal Carcinoma In Situ Lesions.

The aim of this retrospective study was to analyze the predictive capabilities of preoperative mammography, dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) in determining hormone receptor (HRc) status for pure ductal carcinoma in situ (DCIS) lesions. The study included a total of 79 patients who underwent preoperative mammography (MG) and MRI between December 2018 and December 2023 and were subsequently diagnosed with pure DCIS after surgery. The correlation between MG, DCE-MRI, and DWI features and estrogen receptor (ER) and progesterone receptor (PR) status was examined. Among the lesions, 44 were double HRc-positive (ER and PR-positive), 13 were single HRc-positive (ER-positive and PR-negative or ER-negative and PR-positive) and 22 were double HRc-negative (ER and PR-negative). The presence of symptom (p = 0.029), the presence of comedo necrosis (p = 0.005) and high histological grade (p<0.001) were found to be associated with ER and PR negativity. Amorphous microcalcifications were more commonly observed in the double HRc-negative group, while linear calcifications were more prevalent in both double and single HRc-positive groups (p = 0.020). Non-mass enhancement (NME) with a linear distribution was significantly more common in double HRc-negative lesions (38%), and NME with a segmental distribution in both double (43%) and single (50%) receptor-positive lesions (p = 0.042). Evaluation of DWI findings revealed that a higher lesion-to-normal breast parenchyma apparent diffusion coefficient (ADC) ratio statistically increased the probability of HRc positivity (p = 0.033). Certain clinicopathological, mammography, and MRI features, along with the lesion-to-normal breast parenchyma ADC ratio, can serve as predictors for HRc status in DCIS lesions.

Abstract A036: Hair relaxers use and breast cancer risk by tumor estrogen receptor status: Results from the Ghana Breast Health study

Abstract Background: Hair relaxer use is highly prevalent among women of African descent world-wide and in previous analyses within the Ghana Breast Health Study (GBHS) ever use was associated with a 60% elevated risk of breast cancer. Subsequent studies in the GBHS showed selected alterations in estrogen metabolites with hair relaxer use among controls, suggesting a possible hormonal mechanism may underlie the relation of hair relaxers to breast cancer risk. We investigated if the association between relaxer use and breast cancer risk differed by tumor estrogen-receptor (ER) status and hypothesized ever-users would be at a higher risk of ER+ tumors. Methods: The GBHS is a population-based case-control study conducted between 2013– 2015 in Accra and Kumasi of 1,071 cases with pathologically confirmed invasive breast cancer and 2,106 controls, aged 18-74 years. A standardized interview-based questionnaire collected information on currency and duration of use of hair relaxers and whether products used were lye or non-lye formulations. ER status was available for 915 cases, determined using either mRNA expression data from nCounter® Breast Cancer 360™ Panel (65% of 915 cases) or immunohistochemistry. We used multivariable multinomial logistic regression models to estimate odds ratios (OR) with 95% confidence intervals (CI) for ER+ vs. ER- breast cancers. Models were adjusted for age, hospital site, education, body size, age at menarche, parity, age at first birth, median breastfeeding months/child, menopausal status. To determine if risk related to exposure to relaxers differed by ER status, we used logistic regression analyses with ER+ tumors as the reference and calculated heterogeneity p-values (p-het). Results: The majority of women reported ever use of relaxers (96% of cases and 94% of controls). Of the 1,071 cases included in analyses, 422 (44%) were ER+, 438 (41%) ER-, and 156 (15%) unknown for ER. Elevated risk did not differ by ER status for ever compared to never use (OR ER+ =1.67, 95% CI [0.95–2.93]; OR ER - =1.59, 95% CI [0.92–2.76], p-het=0.90). Risks were highest among former users (OR ER+ =2.19, 95% CI [1.21–3.95]; OR ER- =2.21, 95% CI [1.24–3.93], p-het=0.98. Additional analyses showed elevated risk for those with long durations of use, and those who predominantly used non-lye products, but associations did not differ according to ER tumor status. Conclusion: Our analysis of relaxer use in Ghanaian women showed elevated breast cancer risk, particularly for former, long-term users of non-lye formulations, irrespective of tumor ER status. Additional analyses by tumor and other characteristics related to biologically aggressive tumor types needed to determine if associations differ beyond ER consistent with disparities seen in African ancestry women. Further, future research is warranted regarding specific products used that may provide insights into hormonal and non-hormonal mechanisms underlying observed associations. Citation Format: Kaitlin E. White, Quiera Booker, Nicholas Titiloye, Lawrence Edusei, Louise Brinton, Beatrice Wiafe, Ernest Adjei, Jonine Figueroa, On behalf of the Ghana Breast Health Study Team. Hair relaxers use and breast cancer risk by tumor estrogen receptor status: Results from the Ghana Breast Health study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A036.

Abstract A050: The impact of air pollution on aggressive breast cancer prognoses in women of African descent

Abstract Significance. Breast cancer (BC) is the most diagnosed cancer among women in the US. Though highly heterogeneous, different subtypes can be characterized by the expression of membrane receptors on the cell surface: ER+, HER2+, PR+, or basal-like which does not express any of the three receptors. Basal-like triple-negative breast cancer (TNBC) is a highly aggressive subtype of BC that represents about 15% of overall BC cases. Black women disproportionately experience higher rates of early-onset TNBC phenotypes and worse prognoses when compared to White women. Though genetics is a key factor in oncogenesis and cancer progression, it is now widely recognized that differences in cancer outcomes are influenced, also, by various environmental, social, and lifestyle factors known collectively as the social determinants of health (SDOH). For example, air pollution has consistently been shown to be associated with an increased risk of breast cancer, however, little is known about how air pollution alters biological and molecular mechanisms impacting breast cancer progression. Elucidating these influential factors is critical to understanding and addressing disparate outcomes. We are interested in understanding how air pollution impacts immune-oncology related proteins in breast cancer, specifically for Black and White women living in Baltimore City, Maryland. Methods. In a cohort of 217 women (142 Black, 75 White), we performed statistical analyses to determine the correlation between particulate matter 2.5 (PM2.5) with breast cancer subtype and oncogenic molecular drivers within the tumor and its microenvironment. PM2.5 concentration for Census year 2000 was measured using the EPA Downscale Model. Concentrations at the census-tract level were then linked to each participant's geocoded residential address at study baseline. Results. [BJ1] Our data reveal that a higher exposure to PM2.5 is correlated with breast cancer subtypes incidences[BJ2] (p- value[BJ3] =0.051), specifically for hormone receptor positive (ER+ and/or PR+) and TNBC subtypes (p-value=0.035). Elevated air pollution is also associated with estrogen-receptor status overall (p-value=0.002) and in Black (p-value=0.043) and White (p-value=0.008) women in the stratified analysis. Serum protein measurements in this cohort also revealed significant relationships between elevated air pollution and immune-oncology related proteins, including PD-L1, CAIX, CXCL9, and MCP-2.Discussion. Our preliminary evidence reveals an association between air pollution, breast cancer subtypes, and immune-oncology related proteins, with some of these relationships affecting Black and White populations differently. We will continue to interrogate these differences and begin to reveal the underlying mechanisms exacerbating breast cancer disparities. Citation Format: Kayla S. Ingram, Brittany Jenkins-Lord. The impact of air pollution on aggressive breast cancer prognoses in women of African descent [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A050.

A retrospective analysis suggests PTEN expression is associated with favorable clinicopathological features of breast cancer

The phosphatase and tensin homolog (PTEN) gene acts as a tumor suppressor by regulating the PI3K/AKT pathway, crucial for cell growth and survival. Mutations or loss of PTEN are common in breast cancer, leading to uncontrolled cell growth. Understanding PTEN’s role is vital for targeted therapies. 276 formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks from 2012 to 2016 were analyzed for PTEN expression. Immunohistochemistry was performed to identify and assess tumor related clinicopathological characteristics as well as patient demographics. These were statistically matched with PTEN expression. Only 27.5% of the breast cancer tumors were PTEN-positive. PTEN expression correlated significantly with smaller tumor size, lower tumor grade, positive estrogen and progesterone receptor status, and favorable/unfavorable Ki67 status (p < 0.001). No significant association was found with vascular invasion, histologic type, age, HER2 status, staging, or lymph node involvement (p > 0.05). The study confirms PTEN's association with favorable clinicopathological features in breast cancer, supporting its role as a prognostic marker. These findings underscore the importance of PTEN in breast cancer biology and its potential as a therapeutic target. Furthermore these findings confirm the prevalence of advanced stage and aggressive breast cancer tumors in Ghana.

Tumor enhancement and shrinkage pattern in dynamic contrast-enhanced magnetic resonance imaging for predicting pathologic complete response after human epidermal growth factor receptor 2 (HER2)-targeted therapy in breast cancer.

Targeted therapy with neoadjuvant chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer has increased the rates of pathological complete response (pCR) and breast preservation surgery and improved the overall disease-free survival rate. This study aimed to determine whether tumor enhancement and shrinkage patterns in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict the efficacy of targeted therapy in patients with HER2-positive breast cancer and differentiate pCR from non-pCR. The data of 64 patients with HER2-positive breast cancer who received targeted therapy prior to surgery were retrospectively collected. All patients had complete postoperative pathological data. The pretreatment evaluation of the tumor enhancement pattern and the shrinkage pattern after two treatment cycles were assessed. The difference in the enhancement and shrinkage patterns between the pCR and non-pCR groups was evaluated via the χ2 test. Logistic regression analysis was used to assess the value of enhancement and shrinkage patterns for predicting pCR in patients with HER2-positive breast cancer. There were statistically significant differences in tumor size, estrogen receptor (ER) status, lymph node metastasis, enhancement pattern, and shrinkage pattern between the pCR and non-pCR cases. Patients with a tumor size ≤20 mm were likely to achieve pCR. ER status, lymph node metastasis, and enhancement and shrinkage patterns each had good precision for predicting pCR, and the combination of enhancement and shrinkage patterns had the highest prediction accuracy. Multivariate logistic regression analysis indicated that only enhancement pattern had a significant predictive value. Among patients with HER2-positive breast cancer, those with tumor size ≤20 mm, ER-negative status, no lymph node metastases, and mass enhancement and concentric shrinkage patterns are more likely to achieve pCR. Mass enhancement combined with concentric shrinkage had the highest accuracy in predicting pCR, indicating that preoperative imaging may be useful for guiding clinical decisions regarding targeted treatments.

Analysis of HER2 expression changes from breast primary to brain metastases and the impact of HER2-low expression on overall survival.

There are limited data regarding HER2-low expression dynamics between matched primary tumors and brain metastases (BrMs) in breast cancer. HER2-low expression has emerged as a new therapeutic biomarker for highly active antibody-drug conjugates with emerging intracranial activity. Patients with metastatic breast cancer (MBC) and BrMs seen at an NCI-designated center between 2003-2023 were identified. HER2 expression was defined as HER2-positive (3+,2+/ISH amplified), HER2-low (1+,2+/ISH negative), or HER2-0 by ASCO-CAP guidelines. Estrogen receptor (ER) status was defined as ER≥1%. Multivariate survival analyses by Cox proportional hazard models were determined from time of BrM resection to death or last follow-up between the 3 subtypes, controlling for ER and age. Among 197 matched primary and resected BrMs, 81% exhibited HER2 expression in the brain:61% HER2-positive, 20% HER2-low, and 19% HER2-0. Concordance was high in HER2-positive primary tumors with 100% retaining HER2 expression (97% retained HER2+ expression and 2.7% switched to HER2-low). HER2-0 primaries frequently showed HER2 gain in BrMs to HER2-low (35%) or HER2-positive (5.4%) status. Among 48 HER2-low primary tumors, 52% were discordant for HER2 status in the brain with 21% testing HER2-positive and 31% testing HER2-0. In adjusted analyses, patients with HER2-positive BrMs had significantly lower death risk than patients with HER2-low BrMs (HR=0.41, P=0.0006); no difference was observed between HER2-0 and HER2-low. In this retrospective analysis, HER2 expression is common in breast cancer BrMs, emphasizing the need for improved, non-invasive diagnostics. Patients with HER2-low and HER2-0 BrMs face inferior survival, presenting an unmet clinical need.

Prediction of disease-free survival using strain elastography and diffuse optical tomography in patients with T1 breast cancer: a 10-year follow-up study

BackgroundEarly-stage breast cancer (BC) presents a certain risk of recurrence, leading to variable prognoses and complicating individualized management. Yet, preoperative noninvasive tools for accurate prediction of disease-free survival (DFS) are lacking. This study assessed the potential of strain elastography (SE) and diffuse optical tomography (DOT) for non-invasive preoperative prediction of recurrence in T1 BC and developed a prediction model for estimating the probability of DFS.MethodsA total of 565 eligible patients with T1 invasive BC were enrolled prospectively and followed to investigate the recurrence. The associations between imaging features and DFS were evaluated and a best-prediction model for DFS was developed and validated.ResultsDuring the median follow-up period of 10.8 years, 77 patients (13.6%) developed recurrences. The fully adjusted Cox proportional hazards model showed a significant trend between an increasing strain ratio (SR) (P < 0.001 for trend) and the total hemoglobin concentration (TTHC) (P = 0.001 for trend) and DFS. In the subgroup analysis, an intensified association between SR and DFS was observed among women who were progesterone receptor (PR)-positive, lower Ki-67 expression, HER2 negative, and without adjuvant chemotherapy and without Herceptin treatment (all P < 0.05 for interaction). Significant interactions between TTHC status and the lymphovascular invasion, estrogen receptor (ER) status, PR status, HER2 status, and Herceptin treatment were found for DFS(P < 0.05).The imaging–clinical combined model (TTHC + SR + clinicopathological variables) proved to be the best prediction model (AUC = 0.829, 95% CI = 0.786–0.872) and was identified as a potential risk stratification tool to discriminate the risk probability of recurrence.ConclusionThe combined imaging-clinical model we developed outperformed traditional clinical prognostic indicators, providing a non-invasive, reliable tool for preoperative DFS risk stratification and personalized therapeutic strategies in T1 BC. These findings underscore the importance of integrating advanced imaging techniques into clinical practice and offer support for future research to validate and expand on these predictive methodologies.

Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study

BackgroundChemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. cohort. MethodsWe used the U.S. Environmental Protection Agency’s Toxics Release Inventory to estimate historical airborne emissions (1987–1995) of 19 known and probable carcinogens for participants enrolled (1995–1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. ResultsWe observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34–3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92–1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94–1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89–1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01–1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. ConclusionsAn increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.

Characterization of SUSD3 as a novel prognostic biomarker and therapeutic target for breast cancer.

Breast cancer (BC) remains a significant global health challenge, contributing substantially to cancer-related deaths worldwide. Its prevalence and associated death rates remain alarmingly high, highlighting the persistent public health burden. The objective of this study was to systematically examine the involvement of SUSD3 (Sushi Domain-Containing 3) in BC, highlighting its crucial role in the pathogenesis and progression of this disease. BC-related gene microarray data, along with corresponding clinicopathological information, were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Leveraging TIMER and HPA databases, we conducted comparative analyses to evaluate SUSD3 expression in BC. We then analyzed the association between SUSD3 and clinical traits, as well as the prognostic value of SUSD3. SUSD3-related differential expression genes (DEGs) were sent for analysis utilizing GO, KEGG, and GSEA. We utilized SUSD3 mRNA expression to assess immune cells' scores in BC tissues calculated by single-sample enrichment analyses based on "CIBERSORT" R package. Drug sensitivity analysis was used to screen potential drugs sensitive to SUSD3. R software was used for statistical analyses and graphical representation of the data. Our findings confirmed a significant upregulation of SUSD3 expression in BC, which correlated with a favorable prognosis. Clinical correlation analysis further emphasized the strong association between SUSD3 expression and key clinical parameters like estrogen receptor (ER) status, progesterone receptor (PR) status, stage, and T classification in breast cancer. Univariate and multivariate Cox regression analyses showed that SUSD3 could be used as an independent prognostic factor for BC. Differentially expressed genes (DEGs) co-expressed with SUSD3 were significantly associated with various biological processes, such as the cell cycle, DNA replication, p53 signaling pathway, cancer-related pathways, and Wnt signaling pathway, as indicated by gene set enrichment analysis (GSEA). Furthermore, our analysis demonstrated that SUSD3 generally exhibited negative associations with immune modulators. Drug sensitivity analysis revealed positive correlations between SUSD3 and the efficacy of Fulvestrant, Raloxifene, and Fluphenazine. The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.

Predicting the ER Status Using the Gene Expression Profiles

Breast cancer is the most frequently diagnosed malignancy among women globally, making it the leading cause of cancer incidence worldwide. This type of cancer is particularly challenging due to its high degree of molecular heterogeneity, with many different subtypes exhibiting distinct genetic and biological characteristics. Estrogen receptors (ERs) play a crucial role in breast cancer by acting as receptors for the hormone estrogen, often referred to as the hormone receptor (HR). The presence or absence of ERs, known as ER status, significantly impacts treatment decisions, making accurate prediction of ER status essential for personalized treatment plans. Various methods have been proposed in the literature to predict ER status based on gene expression profiles using microarray genome-wide gene expression profiling. The issue of class imbalance, indicated by a notable variation in the number of samples per class and the curse of dimensionality, is a significant concern with microarray datasets. This paper introduces a novel technique, Fuzzy XGBoost, to predict ER status in breast cancer cases while addressing the class imbalance problem. The proposed algorithm enhances the traditional XGBoost method by incorporating fuzzy logic principles, improving its robustness, computational power, and accuracy in handling imbalanced datasets. Our research demonstrates the effectiveness of the proposed Fuzzy XGBoost algorithm in accurately predicting ER status across multiple gene expression profile datasets. This approach not only contributes to advancements in breast cancer treatment but also showcases the power of computational methods in bioinformatics. We evaluate our method using four datasets: GSE2990, GSE3494, GSE6532, and GSE7390, achieving predictive accuracies of 100%, 92%, 100%, and 96%, respectively. The successful application of Fuzzy XGBoost in this context highlights its potential for broader use in bioinformatics, where leveraging computational power to address challenges such as imbalanced data is critical for predictive accuracy and personalized treatment. DOI: https://doi.org/10.52783/pst.619

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review.

Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations is needed to better characterize breast cancer etiologic heterogeneity.

Trends in breast cancer incidence by estrogen receptor status in the United States, 2004-2020.

Divergent trends of breast cancer incidence by subtype have been reported in the United States and elsewhere; however, it remains unknown whether this trend has continued until the era of the COVID-19 pandemic. Using high-quality population-based cancer registry data, representing 83% of the US population, this study examined breast cancer incidence rates by estrogen receptor (ER) status in women aged 20-84 years from 2004 to 2020. The incidence rate of ER-positive cancer increased by 1.75% per year from 2004 to 2009 (95% confidence interval [CI] = 1.26%-3.15%) and has slowed to a 0.87% annual increase (95% CI = 0.41%-1.03%) from 2009 to 2019, followed by a 10.2% reduction from 2019 to 2020. Trends were generally similar across race and ethnicity, although young women (20-49 years), Asian or Pacific Islander, and Hispanic women experienced steady increases until 2019. The incidence rate of ER-negative cancer decreased by 3.13% annually (95% CI = -4.2% to -2.55%) from 2004 to 2012, and the decrease stabilized from 2012 to 2019 (annual percent change: 0.55%; 95% CI = -1.30% to 0.92%), followed by a 6.0% reduction from 2019 to 2020, with trends generally consistent by age and across racial and ethnic groups. The stabilization of the steep decline in ER-negative cancer suggests a departure from the encouraging trajectories projected in earlier studies. Coupled with the deceleration in the rise of ER-positive cancer, the latest trend signals a potential stabilization in the previous rise of the proportional burden of ER-positive cancer. Understanding the impact of the pandemic on each subtype of breast cancer individually may provide a more comprehensive insight into its long-term sequelae on survival and mortality.

Clinicopathological features of breast cancer with HER2 low expression: a real-world retrospective study

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.