Stage Breast Cancer Research Articles

Diagnostic value of salivary tumor markers in breast, lung and ovarian cancer

Background: Breast and ovarian cancers, the most common cancers in women are expected to rise in the next decade. Ovarian cancer is a "silent killer" because of its heterogeneity and asymptomatic early stage. It is currently the fifth most common cause of cancer-related deaths in women, making it the most deadly gynecological malignancy. Objective: To determine the diagnostic value of salivary tumor markers in breast, Lung and Ovarian cancer Methods: A cross-sectional study was conducted at General Hospital Lahore, Pakistan, which was performed between September 2023 to July 2024, The total number of patients in our study were 120. The number of female patients in our study were 120. For all patients, we did diagnostic tests, blood test and Biopsies. We also took the stages of cancer for breast, lung and ovary. We took the symptoms and causes for all patients. We excluded children and pregnant women in our study. Data was tabulated and analyzed by SPSS version 27. Result: In a current study total 120 patients were enrolled. The minimum age of patients were 47 years and the maximum age of the patients were 63 years. The mean age were 54.15±5.354 years. The minimum BMI (Kg/m2) of patients were 31 years and the maximum BMI of the patients were 39 years. The mean BMI were 34.60±2.468 (Kg/m2). The frequency of breast cancer in situ were 3 patients and nill patients were 75 and its percentage were 62%. The breast cancer stage I were present in 12 patients , stage II were 24 patients and Stage III were 6 Patients. P-value were less than 0.04. The frequency of nil patients number in lung cancer were 90 and its percentage were 75%. The frequency of stage I lung cancer were 6 , stage II were 12, stage III were 6 and stage IV were 6 and its percentage were 5%. P-value were <0.02. The frequency of metastasis PM1 in the lung were 5 and in the ovary were 2. Over all P-Value in our study were < 0.05. Conclusion: Saliva would be an excellent diagnostic tool to help cancer patients live longer and with better quality of life. Saliva-omics prove to be a good diagnostic tool for ovarian cancer at early stage. In our study Metastasis PM1 were more in lung as compared to breast and ovary

Hematologic Predictors of Chemotherapy-Induced Neutropenia in Breast Cancer Patients Receiving Anthracycline- or Taxane-Based Chemotherapy

Background: Chemotherapy-induced neutropenia (CIN) is a common and serious complication of chemotherapy in breast cancer patients, leading to increased morbidity, mortality, and treatment disruptions. This study aimed to investigate the association between hematologic profiles and the occurrence of CIN in breast cancer patients receiving anthracycline-based or taxane-based chemotherapy. Methods: A retrospective observational analytic study with a cross-sectional design was conducted using medical records of breast cancer patients treated at the Oncology Surgery Clinic between 2022 and 2023. Sixty patients were included in the study. Hematologic profiles, including hemoglobin and leukocyte counts, were analyzed to assess their association with CIN in both anthracycline- and taxane-based chemotherapy groups. Results: The majority of patients were aged 15-64 years (86.67%), normoweight (65%), had luminal B subtype (63.3%), and were in the locally advanced breast cancer (LABC) stage (45%). Most patients were non-anemic (Hb ≥12 mg/dL) and leukopenic (71.7% and 80%, respectively). No significant association was found between age, nutritional status, or breast cancer stage and CIN (p > 0.05). However, hemoglobin and leukocyte profiles were significantly associated with CIN in both chemotherapy groups (p < 0.05). No association was found between the type of chemotherapy (anthracycline- or taxane-based) and CIN occurrence. Conclusion: Anemia (Hb <12 g/dL) and leukopenia are significant predictors of CIN in breast cancer patients, regardless of the chemotherapy regimen. These findings highlight the importance of monitoring hematologic profiles in these patients to identify those at higher risk of CIN and implement appropriate preventive and management strategies.

The Influence of Physical Training on Breast Cancer: The Role of Exercise-Induced Myokines in Regulating Breast Cancer Cell Growth and Survival

The beneficial impact of physical training in lowering cancer risk is well known. However, the precise mechanisms linking physical training and cancer are not fully understood. Skeletal muscle releases various myokines that seem to possess a direct anti-tumor effect. Although breast cancer (BC) is the prevalent form of cancer among women on a global scale, only limited data are available about the secretion of myokines following exercise in patients with BC. To study the effects of exercise on BC, the blood samples of patients with varied stages of BC were analyzed after 12 weeks of resistance training with whole-body electromyostimulation (WB-EMS). Following the training period, we observed that resistance training helps these patients to improve their physical characteristics and performance function by increasing skeletal muscle mass and strengthening their hand grip. Notably, the patient’s serum was found to inhibit the growth and promote the apoptosis of BC cells in vitro. Moreover, the conditioned medium collected from in vitro stimulated human myotubes using electric pulse stimulation (EPS), an in vitro simulation of WB-EMS training, induced the cell death of BC cells. These results highlighted the direct cancer-protective effects of activated skeletal muscle. In line with our observed effects of serum from exercise-trained pancreatic and prostate cancer patients, the growth of BC cells was notably inhibited when supplemented directly with recombinant myokines C-X-C motif ligand 1 (CXCL1), Interleukin 10 (IL10), and C-C motif chemokine ligand 4 (CCL4). Notably, treatment with these myokines also increased the expression of caspase 3/7 (Casp3/7), resulting in enhanced BC cell death. Our data strongly suggest that physical exercise has a positive impact on skeletal muscle mass and hand grip strength in BC patients, along with a significant anti-tumor effect in BC cells. This shows promising potential for considering sports and physical training as supportive therapies for achieving more impactful cancer treatment.

Investigating the interplay between the mir-183/182/96 cluster and the adherens junction pathway in early-stage breast cancer.

Although the miR-183/182/96 cluster is overexpressed in breast cancer (BC), little is known about its role in the development of pre-carcinogenic lesions which harbor disrupted adherens junctions (AJ) and may promote BC. Here, we used microRNA and RNA sequencing data from The Cancer Genome Atlas (TCGA) Breast Cancer project to investigate the relationship between the miR-183/182/96 cluster and AJ signaling in early-stage BC. We found that all members of the cluster are significantly overexpressed in early-stage BC, the AJ signaling pathway is enriched for genes down-regulated in early-stage BC, and the AJ signaling pathway is enriched for experimentally validated targets of the miR-183/182/96 cluster. The expression of hsa-miR-182 correlates inversely with the mRNA expression of four of its target genes belonging to the AJ signaling pathway: WASF3, EGFR, MET, and CTNNA3. However, the correlations between hsa-miR-182 and AJ gene expression did not differ significantly between targets and non-targets of hsa-miR-182. This suggests that regulatory effects of microRNAs are less pronounced in cancer, as has been shown by other studies. Furthermore, WASF3, EGFR, and MET are oncogenes that tend to be upregulated in later BC stages, implying that the role of some AJ genes changes with different BC stages.

AI Survival Prediction Modeling: The Importance of Considering Treatments and Changes in Health Status over Time

Background and objectives: Deep learning (DL)-based models for predicting the survival of patients with local stages of breast cancer only use time-fixed covariates, i.e., patient and cancer data at the time of diagnosis. These predictions are inherently error-prone because they do not consider time-varying events that occur after initial diagnosis. Our objective is to improve the predictive modeling of survival of patients with localized breast cancer to consider both time-fixed and time-varying events; thus, we take into account the progression of a patient’s health status over time. Methods: We extended four DL-based predictive survival models (DeepSurv, DeepHit, Nnet-survival, and Cox-Time) that deal with right-censored time-to-event data to consider not only a patient’s time-fixed covariates (patient and cancer data at diagnosis) but also a patient’s time-varying covariates (e.g., treatments, comorbidities, progressive age, frailty index, adverse events from treatment). We utilized, as our study data, the SEER-Medicare linked dataset from 1991 to 2016 to study a population of women diagnosed with stage I–III breast cancer (BC) enrolled in Medicare at 65 years or older as qualified by age. We delineated time-fixed variables recorded at the time of diagnosis, including age, race, marital status, breast cancer stage, tumor grade, laterality, estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (HER2) status, and comorbidity index. We analyzed six distinct prognostic categories, cancer stages I–III BC, and each stage’s ER/PR+ or ER/PR− status. At each visit, we delineated the time-varying covariates of administered treatments, induced adverse events, comorbidity index, and age. We predicted the survival of three hypothetical patients to demonstrate the model’s utility. Main Outcomes and Measures: The primary outcomes of the modeling were the measures of the model’s prediction error, as measured by the concordance index, the most commonly applied evaluation metric in survival analysis, and the integrated Brier score, a metric of the model’s discrimination and calibration. Results: The proposed extended patients’ covariates that include both time-fixed and time-varying covariates significantly improved the deep learning models’ prediction error and the discrimination and calibration of a model’s estimates. The prediction of the four DL models using time-fixed covariates in six different prognostic categories all resulted in approximately a 30% error in all six categories. When applying the proposed extension to include time-varying covariates, the accuracy of all four predictive models improved significantly, with the error decreasing to approximately 10%. The models’ predictive accuracy was independent of the differing published survival predictions from time-fixed covariates in the six prognostic categories. We demonstrate the utility of the model in three hypothetical patients with unique patient, cancer, and treatment variables. The model predicted survival based on the patient’s individual time-fixed and time-varying features, which varied considerably from Social Security age-based, and stage and race-based breast cancer survival predictions. Conclusions: The predictive modeling of the survival of patients with early-stage breast cancer using DL models has a prediction error of around 30% when considering only time-fixed covariates at the time of diagnosis and decreases to values under 10% when time-varying covariates are added as input to the models, regardless of the prognostic category of the patient groups. These models can be used to predict individual patients’ survival probabilities based on their unique repertoire of time-fixed and time-varying features. They will provide guidance for patients and their caregivers to assist in decision making.

Breast cancer diagnosis and staging in Chile: A non-randomized survey-based study to assess frequency and delays.

Breast cancer progression involves physiological mechanisms such as metastasis. Delays in diagnosis and treatment increase the risk of mortality and are associated with barriers to healthcare access. In Chile, breast cancer is highly prevalent, and early diagnosis has improved, although disparities in the disease evolution persist. This study characterized diagnostic and staging tests, waiting times, and sociodemographic profiles to identify delays and inequities in care. Survey study. Using a non-probabilistic sample, a questionnaire was applied in an encrypted platform with prior informed consent. The instrument collected data on requested tests, associated times, staging, and sociodemographic characteristics. These variables were analyzed using descriptive statistics, tests of association, confidence intervals, and comparison tests using bootstrapping. A sample of 263 persons was obtained. The most requested tests were biopsy (99.62%) and blood tests (80.23%). The median number of tests requested was six (Q1:4, Q3:8), with a mean of 5.87 (standard deviation: 2.24). No significant differences were observed in the percentage of persons from whom the total number of examinations were requested according to the studied variables. The day-hour-result intervals ranged from 1 to 365 days. The median day-hour-result of the biopsy was 15 days (Q1:10, Q3:30). People between 40 and 49 years old, non-residents of the capital city, belonging to income quintile I, with high school education, from the public health system, with late-stage diagnosis had higher median day-hour-result in biopsy. There was no significant difference in the number of requested tests according to staging (I and II, or III and IV). Biopsy in Chile is the test of choice for diagnostic confirmation in breast cancer. Other tests are requested regardless of the diagnosis stage, contrary to the recommendations of clinical guidelines. Cancer prognosis is crucial, especially in countries with greater inequalities.

De-escalation of Radiation Therapy in the Treatment Plan of Patients with Stage I-IIV Breast Cancer after Subcutaneous/Skin-Sparing Mastectomies with Immediate Reconstruction

Introduction. Indications for radiation therapy after mastectomies with/without reconstruction at T1­2N0­1M0 remain unclear; treatment standards contain references to the possible administration of radiation therapy for factors that increase breast cancer recurrence. Materials and methods. A retrospective single­center, non­randomized study enrolled 984 breast cancer patients treated at P.A. Gertsen Moscow Cancer Research Institute from 2014 to 2022. Patients were divided into 2 groups: a radiotherapy group and a non­radiotherapy group. Results and discussion. The paper presents an analysis of patients’ age, the histological structure of the tumor, immunohistochemical characteristics, tumor grade, multicentricity, presence of lymphovascular invasion, tumor cells, the state of R1 and R0 margins, and the tumor stage at risk of recurrence. Overall survival in the recurrence group accounted for 95.1%, in the non­recurrence group – 98.4%. In the radiotherapy group (group I), the overall survival comprised 98.4%; metastases were diagnosed in 4.9% of cases. In thenon­radiotherapy group (group II), the overall survival amounted to 98.2%; metastases were revealed in 5.9% of cases. Conclusion. Univariate analysis in the study groups showed that radiation therapy reduced the risk of relapse by 3.5%. In case of positive R1 margin, radiotherapy is recommended, which was confirmed in our study, the difference accounted for 14.5%, and in the presence of R1, radiotherapy is claimed to be necessary in the postoperative period. When analyzing the stage of breast cancer and the risk of recurrence, the statistical difference was revealed only at stage IIA (T1N1M0); radiation therapy reduced the risk of breast cancer recurrence. The statistical difference in groups I and II was detected at Grade 2 tumor, Ki­67 level less than 50%, presence of tumor embolism and age of patients under 40 years. Radiation therapy after subcutaneous/skin­sparing mastectomy reduces the recurrence risk by 3.2%; however, the overall survival in group I and group II accounted for 98.4 and 98.2%, respectively; the difference is not statistically significant. In our study, the criteria for prescribing radiation therapy in the postoperative period include: young age of the patients, R1 resection margin, luminal/non­luminal HER2 positive type, cN1, presence of tumor embolism.

[18F]FDG whole-body PET-MR including an integrated breast MR protocol for locoregional and distant staging in breast cancer patients—a feasibility study

PurposeTo investigate in a feasibility study the combination of [18F]FDG whole-body (WB) positron emission tomography-magnetic resonance (PET-MR), including an integrated breast MR within a single protocol for locoregional and distant staging in breast cancer patients.MethodsConsecutive patients with breast cancer diagnoses according to conventional imaging modalities (full-field digital mammography (FFDM) and ultrasound (US)) were prospectively included. All patients underwent [18F]FDG WB PET-MR, including an integrated dedicated breast MR (prone position) and WB PET-MR (supine position) protocol. Results of [18F]FDG WB PET-MR, including integrated breast MR, versus conventional imaging modalities were compared.ResultsFrom April 2021–April 2022, 28 patients were included. On conventional imaging, cT1-2 breast cancer was present in 22 (FFDM) and 23 (US) out of 28 patients. With regard to clinical nodal status, eight patients were considered cN0, eighteen cN1 (1-3 suspicious lymph nodes), and two patients were cN2 (four suspicious axillary lymph nodes/internal mammary lymph node metastasis). [18F]FDG WB PET-MR, including an integrated breast MR protocol, upstaged clinical tumor status in two patients and clinical nodal status in nine patients according to both [18F]FDG WB PET-MR and breast MR findings. In addition, distant metastases were detected in three patients (liver/bone), and another patient was diagnosed with a synchronous primary tumor (lung cancer).Conclusion[18F]FDG WB PET-MR, including an integrated breast MR within a single protocol in breast cancer patients, is feasible and provides a promising new approach in breast cancer patients with regard to locoregional and distant staging.Critical relevance statement[18F]FDG whole-body PET-MR, including an integrated breast MR protocol, is feasible and allows locoregional and distant staging within a single imaging exam in breast cancer patients.Key Points[18F]FDG PET-MR allows the combination of breast MR and whole-body staging.Therefore, a single protocol of whole-body [18F]FDG PET-MR, including an integrated breast MRI, is investigated.[18F]FDG PET-MR, including an integrated breast MR is feasible and can be considered in daily clinical practice.Graphical

Transcriptomic markers of biological aging in breast cancer survivors: a longitudinal study.

The purpose of this study was to examine the impact of breast cancer therapy on biological aging as measured by expression of genes for cellular senescence (p16INK4a, SenMayo), DNA damage response, and proinflammatory senescence-associated secretory phenotype. This longitudinal, observational study evaluated women diagnosed with breast cancer (stage 0-III) prior to radiation therapy (RT) and/or chemotherapy (CT) and at repeated visits out to 2 years. Peripheral blood mononuclear cell gene expression was assessed using RNA sequencing on quality-verified RNA. Longitudinal data were analyzed using mixed linear models and a zero-inflated 2-part model. Women (mean age = 55.5 years) receiving CT with or without RT (n = 73) had higher odds (odds ratio = 2.97, 95% confidence interval = 1.52 to 5.8) of having detectable p16INK4a following treatment compared with RT (n = 76) or surgery alone (n = 37). The proportion of women expressing 16INK4a over the follow-up period increased in all treatment groups (P < .001), with no interaction by treatment. All groups also increased over time in DNA damage response (P < .001), SenMayo (P < .001), and senescence-associated secretory phenotype (P < .001). Groups differed in the pattern of increase over time with statistically significant quadratic time by group differences for CT with or without RT compared with RT alone for DNA damage response (P = .05), SenMayo (P = .006), and the senescence-associated secretory phenotype (P = .02). Results revealed activation of genes associated with biological aging in women with breast cancer from diagnosis through early survivorship, including DNA damage response, cell senescence, and the inflammatory secretome. Increases were evident across cancer treatments, although women receiving CT showed sustained increases, whereas RT exhibited slowing at later time points. Overall, findings suggest that women treated for breast cancer are aging within their immune cells.

Role of bone scan for investigation of breast cancer and its applicability in future management.

Objective: To find out the usefulness of bone scan in all stages of breast cancer. Study Design: Prospective Observation Study. Setting: Surgical Unit I &amp; III Ghulam Muhammad Mahar Medical College Hospital, Sukkur. Period: October 2020 till September 2022. Methods: A total of 300 patients were selected who were newly diagnosed with breast cancer (Biopsy Proven). Data was collected for all these patients which included age, risk factors for breast cancer, findings on local examination, histopathology findings, stage of the cancer and result of the bone scan. Results: In our study, 78% patients were in 4th and 5th decade of life with mean age of 53.46±7.66 years. ‘Age above 40’ was the commonest risk factor for breast cancer followed by positive family history for breast cancer. Tumor size ranged from 2 to 13.2 cm with mean size of 6.06±1.92 cm. In our study, most common type of carcinoma was invasive ductal carcinoma (71.3%) followed by invasive lobar carcinoma (50%). Only 32 (10.67%) out of 300 patients had positive bone scan. Majority of the bone scan positive cases belonged to the Stage IIIB, IIIC and IV. Conclusion: It is concluded in our study that routine use of bone scan in cases of stage 1 and 2 breast cancer is not recommended; only stage 3A or advances cases should undergo bone scan.

Decision tree insights analytics (DTIA) tool: an analytic framework to identify insights from large data records across fields of science

Abstract Supervised machine learning (SML) techniques have been developed since the 1960s. Most of their applications were oriented towards developing models capable of predicting numerical values or categorical output based on a set of input variables (input features). Recently, SML models’ interpretability and explainability were extensively studied to have confidence in the models’ decisions. In this work, we propose a new deployment method named Decision Tree Insights Analytics (DTIA) that shifts the purpose of using decision tree classification from having a model capable of differentiating the different categorical outputs based on the input features to systematically finding the associations between inputs and outputs. DTIA can reveal interesting areas in the feature space, leading to the development of research questions and the discovery of new associations that might have been overlooked earlier. We applied the method to three case studies: (1) nuclear reactor accident propagation, (2) single-cell RNA sequencing of Niemann-Pick disease type C1 in mice, and (3) bulk RNA sequencing for breast cancer staging in humans. The developed method provided insights into the first two. On the other hand, it showed some of the method’s limitations in the third case study. Finally, we presented how the DTIA’s insights are more agreeable with the abstract information gain calculations and provide more in-depth information that can help derive more profound physical meaning compared to the random forest’s feature importance attribute and K-means clustering for feature ranking.

6550 National Statin Prescription Trends in Patients With Breast Cancer and Diabetes for Primary Cardiovascular Disease Prevention

Abstract Disclosure: A.B. Yang: None. G. Mhango: None. C. Kong: None. J.J. Lin: None. J.P. Wisnivesky: Consulting Fee; Self; Sanofi, Banook, PPD. Grant Recipient; Self; Sanofi, Regeneron Pharmaceuticals, Axella, Arnold Consultants. A. Leiter: None. Background: Cardiovascular disease (CVD) is the leading cause of death in older early-stage breast cancer (BC) survivors. Due to cardiotoxic BC treatments such as chemotherapy and radiation, patients with BC and diabetes (DM) are at increased risk of CVD. In patients with BC and DM, statins decrease CVD mortality. Since 2013, many clinical guidelines broadened statin indications for primary CVD prevention in patients with DM, making &amp;gt;85% of patients eligible. Little is known about statin prescription (Rx) patterns in older BC survivors with DM, a group at high risk of CVD. Hypothesis: We hypothesized that statin Rxs increased over time, but were less likely in BC survivors with more advanced locoregional BC and lower comorbidity burden. Methods: A population-based, retrospective cohort study was conducted using Surveillance, Epidemiology and End Results (SEER) cancer registry data linked to Medicare claims. We identified women with preexisting DM who were diagnosed with stage 0-III primary BC between 2008-17. We excluded patients with prior CVD who died &amp;lt;1 year after BC diagnosis. Statin Rx (atorvastatin, pravastatin, rosuvastatin, simvastatin, fluvastatin, lovastatin) was defined as ≥1 statin pharmacy claim &amp;lt;1 year after BC diagnosis. Comorbidity burden was assessed with a modified Charlson Comorbidity Index (CCI). We compared patient demographic and clinical characteristics by statin Rx status using the chi-square test. Using a multivariate logistic regression adjusting for age, race, CCI, BC stage, and diagnosis year, independent predictors of statin Rx were identified. Results: Of 8,423 BC patients with pre-existing DM, 5,698 (68%) had a statin Rx. Statin Rx increased over time (BC diagnosis year 2008-10: 66%, 2011-13: 66%, 2014-15: 69%, 2016-17: 70%; p=0.01) and differed by age (66-69: 66%, 70-74: 70%, 75-79: 69%, ≥80: 65%; p&amp;lt;0.01) and race (White: 68%, Black: 62%, Latinx: 66%, Other: 72%; p&amp;lt;0.01). Statin Rx did not differ by comorbidity burden (CCI 0: 68%, 1-2: 67%, ≥3: 67%; p=0.87) and declined with higher BC stage (0: 73%, I: 70%, II: 65%, III: 63%; p&amp;lt;0.01). In adjusted analyses, more recent BC diagnosis (2016-17 vs. 2008-10: odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.04-1.38), age group (70-74 vs. 66-69: OR: 1.24, 95% CI: 1.09-1.41), race (Black vs. White: OR 0.77, 95% CI: 0.66-0.89) and higher BC stages (II vs. 0: OR: 0.76, 95% CI: 0.58-1.00; III vs. 0: OR: 0.72, 95% CI: 0.54-0.97) remained predictors of statin Rx. Conclusions: In a nationally representative cohort analysis of older early-stage BC patients, statin Rx increased between 2008-17 and varied by age, race, and BC stage. Elucidating gaps in statin Rx can potentially improve guideline-concordant Rx in a group at high risk for CVD and reduce disparities. Presentation: 6/2/2024

6931 Weight Trends and Predictors of Weight Gain in Breast Cancer Survivors

Abstract Disclosure: M.D. Hurtado: None. E. Tama: None. D. Hodge: None. A. Weston: None. S. Fahad: None. K. Ruddy: None. J. Olson: None. F. Coach: None. R. Carter: None. S. D'Andre: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. Background: Breast cancer (BC) is the most common cancer in women. Weight gain after treatment for early-stage BC is associated with a higher risk of recurrence. Excess adiposity is also a major risk factor for cardiovascular disease, the leading cause of non-BC related death in BC survivors. This study aimed to describe weight trends in a large cohort of BC survivors and to identify predictors of weight gain after BC diagnosis. Methods: This was a retrospective study of BC survivors from the prospectively consented Mayo Clinic Breast Cancer Registry, which has enrolled &amp;gt;10,000 patients seen at least once at Mayo Clinic Rochester for a BC diagnosed within the prior year. We extracted data on weights at baseline, and years 1, 4, and 6 after BC diagnosis to generate longitudinal weight trajectory curves on the change from baseline. Weights were either reported by patients in the registry questionnaires or extracted from the electronic health records. We identified BC survivors with weight gain &amp;gt;10% from baseline weight at years 1, 4, and 6. We then conducted univariable logistic regression analyses to identify predictors of &amp;gt;10% weight gain. Variables considered included: demographics, anthropometrics, BC clinical and pathologic characteristics, BRCA 1 and 2 genetic mutation status, and treatment (surgery, neoadjuvant or adjuvant chemotherapy, and/or radiotherapy). Results: We included 4744 BC survivors, mostly white (95%) and non-Hispanic (91%), with a mean age and weight at BC diagnosis of 58 ± 13 years and 76 ± 18 kg. Most patients had clinical stage I (43%) and ER+ and PR+ BC (83% and 76%, respectively). Most patients underwent breast preserving surgery (62%), half received radiation (54%), one third (36%) received systemic chemotherapy, and two thirds (61%) received endocrine therapy. At one year after BC diagnosis the average weight change was negligible compared to baseline (mean difference -0.2 ± 8 kg), but there were small but significant average increases by years 4 and 6 (0.5 ± 9 kg, p=0.002; and 0.8 ± 10 kg, p&amp;lt;0.001; respectively). At years 1, 4, and 6, the percentage of BC survivors gaining &amp;gt;10% of their baseline weight was 10%, 15%, and 18%, respectively. Baseline characteristics associated with &amp;gt;10% weight gain at 6 years included lower baseline weight (p&amp;lt;0.001), younger age at BC diagnosis (p&amp;lt;0.001), more advanced clinical and pathologic BC stage (p=0.008), ER+ and PR+ tumor biology (p=0.02 for both), BRCA2 mutation (p&amp;lt;0.001), mastectomy (compared to breast preserving surgeries, p=0.008), the use of systemic chemotherapy treatment (p&amp;lt;0.001), and the use of endocrine therapy (p=0.03). Conclusion: While most BC survivors do not experience weight gain after survivorship, 1 out 5 may experience excessive weight gain of more than 10%. Baseline anthropometric and BC-related variables are associated with excessive weight gain and could be used as predictors of weight gain in this population. Presentation: 6/3/2024

Single-cell transcriptome analysis reveals immune microenvironment changes and insights into the transition from DCIS to IDC with associated prognostic genes

BackgroundDuctal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood.ResultsWe identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers.ConclusionsWe identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

Race/ethnicity and human epidermal growth hormone receptor 2–targeted therapy for breast cancer.

91 Background: Breast cancer is the most common cancer in the US. Up to 25% of breast cancers are classified as human epidermal growth factor receptor 2 (HER2)-positive and associated with an aggressive tumor burden. HER2-targeting monoclonal antibodies improves survival in patients with HER2-positive breast cancer. Prior work has demonstrated disparities in access to oncologic therapies among older women. Our study seeks to examine racial/ethnic disparities in receiving HER2-targeted therapies for patients with HER2-positive breast cancer and trends in use over time. Methods: In the Surveillance, Epidemiology and End Results (SEER) Medicare-linked database we identified women diagnosed with breast cancer from 2010 to 2019. We included those &gt;66 years old who survived 12 months after diagnosis, were enrolled in Medicare Parts A/B for 12 months pre and post-diagnosis, and had local or regional stage HER2-positive cancer. Our primary outcome was receipt of HER2-targeted therapies in the 12 months after diagnosis. Our independent variable was race/ethnicity as measured by the validated Research Triangle Institute race/ethnicity codes in Medicare. Due to small sample sizes, we focus our analysis on White, Black, or Hispanic women. We used multivariable Modified Poisson regression to evaluate changes in the probability of HER2-targeted therapy receipt by race/ethnicity over time, adjusted for sociodemographics, cancer factors, and medical comorbidities. Results: Our cohort comprised 13,887 patients including 8.7% Black, 7.5% Hispanic, and 83.8% White (mean age 74.9). Overall, 7,351 (52.9%) received HER2-targeted therapies in the 12 months post-diagnosis, with use increasing over time in all racial/ethnic groups (Table). Compared with White patients, Black and Hispanic patients had a 19% (adjusted risk ratio [aRR] 0.81, 95% CI:0.69-0.96) and 27% (aRR 0.73, 95% CI 0.61-0.89) lower likelihood, respectively, of receiving HER2-targeted therapies from 2010-2011 (Table). By 2018-2019, no significant differences in receiving HER2-targeted therapies were observed across racial/ethnic groups. Conclusions: In a national cohort of Medicare enrollees with HER2-positive breast cancer, we observed significant racial/ethnic disparities which narrowed over time. Overall utilization rates were low. Future work is needed to understand how improved access to breast cancer treatments impact downstream outcomes. Use of human epidermal growth hormone receptor 2–targeted therapy from 2010-2011 and 2018-2019 by race/ethnicity. Race and Ethnicity Unadjusted Rates Adjusted Risk Ratios (95% CI)* 2010-2011 2018-2019 2010-2011 2018-2019 Black 36% 62% 0.81 (0.69-0.96) 0.97 (0.87-1.08) Hispanic 31% 68% 0.73 (0.61-0.89) 1.01 (0.92-1.12) White 42% 64% Reference Reference *Adjusted for age, marital status, region, breast cancer stage and year of diagnosis, and medical comorbidities.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Breast cancer statistics 2024.

This is the American Cancer Society's biennial update of statistics on breast cancer among women based on high-quality incidence and mortality data from the National Cancer Institute and the Centers for Disease Control and Prevention. Breast cancer incidence continued an upward trend, rising by 1% annually during 2012-2021, largely confined to localized-stage and hormone receptor-positive disease. A steeper increase in women younger than 50 years (1.4% annually) versus 50 years and older (0.7%) overall was only significant among White women. Asian American/Pacific Islander women had the fastest increase in both age groups (2.7% and 2.5% per year, respectively); consequently, young Asian American/Pacific Islander women had the second lowest rate in 2000 (57.4 per 100,000) but the highest rate in 2021 (86.3 per 100,000) alongside White women (86.4 per 100,000), surpassing Black women (81.5 per 100,000). In contrast, the overall breast cancer death rate continuously declined during 1989-2022 by 44% overall, translating to 517,900 fewer breast cancer deaths during thistime. However, not all women have experienced this progress; mortality remained unchanged since 1990 in American Indian/Alaska Native women, and Black women have 38% higher mortality than White women despite 5% lower incidence. Although the Black-White disparity partly reflects more triple-negative cancers, Black women have the lowest survival for every breast cancer subtype and stage except localized disease, with which they are 10% less likely to be diagnosed than White women (58% vs. 68%), highlighting disadvantages in social determinants of health. Progress against breast cancer could be accelerated by mitigating racial, ethnic, and social disparities through improved clinical trial representation and access to high-quality screening and treatment.

The Social Reality of Meaning Making: The Dichotomy in the Illness Narratives of Women With Breast Cancer and Biomedical Practitioners in Nigeria.

Despite the increasing burden of breast cancer in the developing world, there is a misunderstanding of the complex and multifaceted relationship between culture and cancer, particularly breast cancer. Hence, a dichotomy of illness narratives exists due to differential meaning making concerning breast cancer. While clinicians always recommend biomedical treatment, women with breast cancer often seek alternative treatment pathways. To explore the experiences of women with breast cancer and clinicians in Nigeria on the dichotomy in the illness narratives. This qualitative study used in-depth interviews and focus group discussion to explore the experiences of 22 women with breast cancer and 7 clinicians in Nigeria on the dichotomy in the illness narratives using grounded theory method analysis. This study revealed that many women living with breast cancer (WLBC) hold health beliefs that are contradictory to the biomedical norm. They mostly sought treatment based on the perceived aetiology of breast cancer. The treatment pathway follows faith and traditional healing as alternatives or sometimes in combination with biomedicine. WLBC reported a constant fear of biomedical treatment, perceived to be harmful to women's sexuality, fertility and body image. Hence, after perceived treatment failure from alternative care, biomedical care becomes the last resort, usually at an advanced stage of breast cancer, often responsible for poor prognosis. There is a dichotomy of illness construction between sufferers and health practitioners. To guide women with breast cancer on the path of care, modern care practitioners should consider some cultural norms and practices without compromising professional ethos.

TRPV2 calcium channel promotes breast cancer progression potential by activating autophagy

Breast cancer, the most prevalent and aggressive tumor affecting women, requires identification of disease determinants to facilitate the development of effective therapeutic strategies. Transient receptor potential vanilloid 2 (TRPV2), an ion channel highly permeable for calcium (Ca2+), is implicated in physiological and pathological processes. Nevertheless, the role of TRPV2 in breast cancer remains poorly elucidated. In this study, we found high levels of TRPV2 expression associated with advanced malignancy, thereby suggesting its potential as a biomarker for breast cancer staging. We demonstrated that TRPV2 activation promotes breast cancer cell proliferation, migration, and invasion, while silencing of TRPV2 suppresses breast cancer progression, highlighting the oncogenic role of TRPV2. Moreover, we reveal that TRPV2 facilitates cancer progression by modulating the CaMKKβ/AMPK/ULK1-autophagic axis through mediating calcium influx, providing new insights into TRPV2 as a novel therapeutic target for breast cancer treatment.

The EORTC 22922/10925 trial investigating regional nodal irradiation in stage I-III breast cancer: Outcomes according to locoregional and systemic therapies

The EORTC 22922/10925 trial aimed to investigate the impact on overall survival (OS) of elective internal mammary and medial supraclavicular (IM-MS) radiation therapy (RT) in breast cancer stage I–III. Surgery for the primary tumour and axillary lymph nodes, chest wall RT, boost RT after whole breast RT in breast conserving therapy (BCT), RT to operated axilla, and systemic therapy were per physician’s preference. The aim of the current analysis is to assess breast cancer outcomes according to different locoregional and systemic therapy used in the trial. Material/MethodsData with a median follow-up of 15.7 years were extracted from the trial’s case report forms. Kaplan-Meier curves of disease-free and OS and cumulative incidence curves of breast cancer events were produced. An exploratory analysis of the effect of the type of locoregional and systemic therapy on breast cancer outcomes was conducted using the Cox model or the Fine & Gray model accounting for competing risks, both models being adjusted for baseline patient and disease characteristics and treatment. The significance level was set at 5 %, 2-sided. ResultsOf the 4,004 patients included, 625 (16%) did not receive any postoperative systemic therapy, 1,185 (30%) received endocrine therapy only, 994 (25%) chemotherapy only, and 1,200 (30%) both chemotherapy and endocrine therapy, without differences between the randomisation arms.Administration and type of therapy was associated with age, menopausal status, clinical T- and N-stage and ER status (p < 0.0001). Local control was better with mastectomy (with/without postmastectomy RT) as compared to BCT, but mastectomy was associated with more distant metastasis (DM) as first event. Similarly, DM as first event occurred more in the BCT group that received a boost as compared to no boost and in those who received RT to the lower axillary level. IM-MS RT reduced significantly regional recurrences and improved disease-free survival in a sensitivity stratified analysis. OS was worse with mastectomy as compared to BCT and with irradiation of the axilla but better with sentinel node dissection and adjuvant combined chemo and hormonal therapy. ConclusionDifferent components of therapy influenced the site of first event. IM-MS RT improved outcomes in different breast cancer outcomes were most probably related that the group were balanced due to the trial arms and stratification methods.