Proportion Of Breast Cancer Patients Research Articles

Abstract PO4-18-12: MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411)

Abstract Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support will be provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Nina Ditsch, Antonio Esgueva, Neslihan Cabıoğlu, Dawid Murawa, Nuh Zafer Canturk, Isabel Rubio, Jana de Boniface, Andreas Karakatsanis, Rajiv Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael P. Lux, Tove Tvedskov, Lina Pankratjevaite, Michalis Kontos, Florentia Peintinger, Aoife Lowery, Marjolein Smidt, Lia Rebaza, Maria Vasconcelos, Bahadir M. Gulluoglu, Bilge Aktas Sezen, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Maria Luisa Gasparri, Séverine Alran, SVS Deo, Mah Muneer Khan, James Harvey. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-12.

Abstract PO2-27-07: The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients

Abstract Human Cytomegalovirus (HCMV) infection has emerged as a noteworthy factor in breast cancer patients, particularly those experiencing brain metastasis. Despite being prevalent and often asymptomatic, HCMV's contribution to tumor progression remains enigmatic. Notably, a high proportion of breast cancer patients with brain metastasis exhibit HCMV positivity in both primary tumors and metastatic lesions. This study aims to elucidate the influence of HCMV infection on brain metastasis by investigating its impact on the tumor microenvironment. Our findings reveal a distinctive immune suppressive tumor microenvironment in HCMV-positive breast cancer patients. This environment is characterized by impaired NK cell function and an elevated accumulation of TH2 cells. To comprehend the role of HCMV in promoting brain metastasis, we have developed a murine breast tumor model using MCMV, enabling us to mirror the clinical trajectory of tumor progression and metastasis. The integration of a GFP reporter gene into the MCMV genome facilitates the tracking of infected cancer cells. Within this model, we observe a significant increase in brain metastasis coupled with reduced survival rates. Single-cell sequencing analysis uncovers diminished NK cell presence and activation, along with heightened TH2 cell accumulation within the tumor microenvironment—results that parallel the clinical observations in breast cancer patients. GSEA analysis underscores the secretion of inhibitory cytokines by MCMV-infected cancer cells, contrasting with their non-infected counterparts. Collectively, our study reveals that CMV infection contributes to brain metastasis in breast cancer by generating inhibitory cytokines. This hampers the recruitment and proliferation of immune cells within the tumor microenvironment and concurrently impairs the cytotoxic capabilities of NK cells. These insights shed light on the intricate interplay between viral infection and tumor progression, offering potential avenues for therapeutic exploration. Citation Format: Wenjuan Dong, Xin Wang, Kun Han, Akshjot Puri, Amna Irfan, Wei Qian, Liliana Guzman, Roberto Rosato, Jianting Sheng, Hong Zhao, Jenny Chang, Stephen Wong. The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-07.

Avoidable emergency department visits among palliative care cancer patients: novel insights from Saudi Arabia and the Middle East

BackgroundSeveral studies emerging from developed countries have highlighted a significant number of potentially avoidable emergency department (ED) visits by cancer patients during the end-of-life period. However, there is a paucity of information from developing nations regarding palliative care practices and the utilization of the ED by palliative care patients. Herein, we aim to characterize ED admissions among patients receiving palliative care at our tertiary center in Saudi Arabia.MethodsThis is a retrospective, cross-sectional study evaluating ED visits amongst adult patients with advanced cancer who were receiving treatment under the palliative care department. This study took place over a period of 12 months from July 2021 through to July 2022. Three palliative care specialist physicians independently and blindly reviewed each patient’s ED visits and determined whether the visit was avoidable or unavoidable.ResultsA total of 243 patients were included in the final analysis, of which 189 (78.1%) patients had unavoidable visits and 53 (21.9%) patient visits were classified as avoidable. A significantly higher proportion of breast cancer patients presented with unavoidable admissions (14.3% vs. 3.8%, P = 0.037) compared to other cancer types. The incidence of dyspnea (23.8% vs. 5.7%, P < 0.001) and fevers/chills (23.3% vs. 5.7%, P = 0.005) was significantly higher in patients with unavoidable visits. Patients with avoidable visits had a significantly greater proportion of visits for dehydration (13.2% vs. 2.1%, P = 0.002). Notably, although hospital stay was significantly longer in the unavoidable group (P = 0.045), mortality for palliative care patients—regardless of whether their ED visit was avoidable or unavoidable—was not statistically different (P=-0.069).ConclusionTo our knowledge, this is the largest and most comprehensive study from Saudi Arabia and the Middle East providing insights into the utilization of palliative care services in the region and the propensity of advanced cancer patients towards visiting the ED. Future studies ought to explore interventions to reduce the frequency of avoidable ED visits.

Tumor Ki-67, ER and PR, and antibodies against estradiol and progesterone in breast cancer patients

Aim. To investigate the associations of cell proliferation marker Ki-67 in estrogen receptor (ER) and progesterone receptor (PR) positive (ER+/ PR+) and negative (ER-/PR-) tumors with the ratio of antibodies against estradiol and progesterone (IgA1-E2/IgA1-Pg) in the serum of breast cancer (BC) patients.Materials and Methods. Antibodies against steroid hormones were analyzed by ELISA in the serum of 432 healthy women and 1212 patients with BC (573 patients with I stage and 639 patients with II–IV stages). Expression of Ki-67, ER and PR in tumors was determined by immunohistochemical staining. Serum estradiol and progesterone were measured by enzyme-linked immunosorbent assay.Results. In total, low IgA1-E2/IgA1-Pg (≤ 1) and high IgA1-E2/IgA1-Pg (&gt; 1) ratio were revealed in 49.3% and 50.7% of healthy women; in 25.7% and 74.3% of stage I BC patients with tumor Ki-67 &lt; 14 (р &lt; 0.001; OR = 0.4 and OR = 2.8, respectively), and in 17.1% and 82.9% of stage I BC patients with tumor Ki-67 &gt; 30 (р &lt; 0.001; OR = 0.2 and OR = 4.7, respectively). The differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA1-E2/IgA1-Pg ratio were statistically significant (p = 0.03). In stage I BC patients with ER+/PR+ and tumors with Ki-67 &lt; 14, low and high IgA1-E2/IgA1-Pg ratio were found in 25.0% and 75.0% cases (р &lt; 0.001; OR = 0.3 and OR = 2.9, respectively). In stage I BC patients with ER+/PR+ and tumors with Ki-67 &gt; 30, low and high IgA1-E2/IgA1-Pg ratio were found in 12.9% and 87.1% cases (р &lt; 0.001; OR = 0.2 and OR = 6.6, respectively). In patients with ER+/PR+ tumors, the differences between patients with low and high tumor Ki-67 levels in relation to low and high IgA1-E2/IgA1-Pg ratio were also statistically significant (p = 0.009). In patients with ER-/PR- tumors, the differences between patients with low and high Ki-67 levels in relation to low and high IgA1-E2/IgA1-Pg ratio were not revealed. The proportion of breast cancer patients with tumor Ki-67 &gt; 30 increased from I to II–IV BC stages regardless of IgA1-E2/IgA1-Pg ratio.Conclusion. IgA1-E2/IgA1-Pg ratio may serve as a predictor of tumor proliferative activity in stage I BC patients with ER+/PR+ tumors.

Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls.

Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown. Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants. Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes. Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical implications for women who undergo genetic testing and be pivotal for a substantial proportion of breast cancer patients in Cyprus.

Sociodemographic disparities associated with advanced stages and distant metastatic breast cancers at diagnosis in Indonesia: a cross-sectional study.

The global health burden of breast cancer is increasing with 5-year survival rates being much shorter in low-income and middle-income countries. Sociodemographic and clinical disparities in early cancer detection affect long-term outcome. The authors compared social, demographic, and pathological characteristics associated with metastatic and late stages of breast cancer diagnosis using data collected from a special registry developed by Perhimpunan Bedah Onkologi Indonesia (PERABOI) in 2015. Of 4959 patients recruited in this study, 995 women (20.1%) were diagnosed with metastatic breast cancer. Lower education status and living in rural areas were significantly associated with Stage IV at diagnosis [odds ratio (OR)=1.256, 95% CI=1.093-1.445, P=0.001; and OR=1.197, 95% CI=1.042-1.377, P=0.012; respectively). Main complaints other than lump (ulceration, breast pain, and discharge) and occupation as a housewife were also associated with the presentation of metastatic diseases (OR=2.598, 95% CI=2.538-3.448, P<0.001 and OR=1.264, 95% CI=1.056-1.567, P=0.030, respectively). Having lower education and living outside Java and Bali islands were associated with the diagnosis of late-stage breast cancers (OR=1.908, 95% CI=1.629-2.232, P<0.001 and OR=3.039, 95% CI=2.238-4.126, P<0.001; respectively). A higher proportion of breast cancer patients were relatively younger with bigger tumour size, positive axillary nodal involvement, and more frequent Human epidermal growth factor receptor 2 overexpression. The authors identified sociodemographic disparities in the metastatic and late-stage diagnosis of breast cancers among Indonesian women. The subsequent action is required to reduce disparities faced by women with lower social and educational levels for early diagnosis and better healthcare access.

EVALUATION OF THE ACTIVITY OF PERIPHERAL BLOOD NATURAL KILLER CELLS IN HEALTHY SUBJECTS AND BREAST CANCER PATIENTS

Objectives: To study Natural Killer (NK) cell activity (NK-IFNg) and some indicators related to immunological characteristics of peripheral blood NK cells in healthy people and breast cancer patients. Methods: We evaluated NK cell activity through its secretory characteristics (NK-IFNg) using ATGen's commercial NK VUE TestÒ (ATGen kit) on 35 healthy subjects (medical staff) and 132 cancer patients treated at Vietnam National Cancer Hospital from August 2020 to February 2023. At the same time, we collected peripheral blood samples to conduct immunological characterization of peripheral blood NK cells based on the flow cytometer system (number, expression of the activation and inhibitory receptors such as NKG2A, NKG2D), and some other biomarkers (CEA, CA 15.3). Results: The secretory activity of peripheral blood NK cells (NKA-IFNγ) in breast cancer patients (1,013.46 ± 1,115.87 pg/mL) was statistically significantly lower than that in the healthy group ( 2,571.38 ± 827.52 pg/mL) ( ± SD) (p &lt; 0.001). The proportion of breast cancer patients with NKA-IFNγ activity of a very low level (≤ 200 pg/mL) was 40.9% and that of the healthy subjects was 0%. There was no relationship between NKA-IFNγ and peripheral blood NK cell count, and the expression levels of the activating receptor NKG2D and the inhibitory receptor NKG2A. Patients with CEA and CA 15.3 serum levels above the normal limits accounted for relatively low percentages (10.6% and 6.1%). Conclusion: Breast cancer patients with very low NK cell activity accounted for a significant proportion (40.9%). NKA-IFNγ activity could be used as a potential tool for monitoring the immune system health status of breast cancer patients before and after receiving treatment interventions.

Multifaceted Networking of The Orphan Receptor Estrogen-Related Receptor Β in Breast Cancer Progression

Breast cancer death polls are rising at an alarming rate in females globally. It is a hormone-dependent disease that is majorly regulated by estrogen. Several genetic and environmental factors are the primary attributes of breast cancer growth and development. A higher proportion of breast cancer patients harbor estrogen receptor-positive (ER+ve) status. Estrogen related receptors are orphan nuclear receptors which include ERRα, ERRβ, and ERRϒ that exhibit a sequence similarity with ERα. ERRα and ERRϒ act as activators in cancer. ERRβ expression is downregulated in breast cancer cells and patient samples, compared to healthy breast cells. The decreased expression of ERRβ is primarily mediated by the proteasomal pathway at the protein level. ERRβ restricts cell cycle progression in breast cancer cells, thereby impeding breast cancer proliferation. Neddylation of ERRβ mediates its downregulation which triggers the oncogenic signalling in breast cancer. Our study showed employing MLN4924, an NAE inhibitor to restore the expressivity of ERRβ could provide a successful and cutting-edge therapeutic method. This review article illustrates the regulatory role of ERRβ in the formation and evolution of breast cancer, making it an effective therapeutic candidate.

Exploring the unmet needs of Mexican women living with metastatic breast cancer: A patient survey.

e24223 Background: Breast cancer is the most prevalent form of cancer among women worldwide and the top cause of cancer-related fatalities. In Mexico, delayed diagnosis and referral contribute to a significant proportion of breast cancer patients being diagnosed with metastatic breast cancer (mBC) or experiencing distant recurrences. Patients with mBC face unique needs and concerns for their illness, which are frequently not attended to or covered. Gaining insight into their diagnostic experiences is crucial for enhancing the standard of care. The aim of this study is to explore the unmet needs of Mexican women living with mBC. Methods: An anonymous and voluntary survey was distributed to women diagnosed with mBC. The instrument employed was drawn from the European "Being There" study and underwent translation into Spanish in accordance with the current best practices for the translation and cultural adaptation of health measurement tools. The survey addressed various subjects including patient’s personal experiences concerning diagnosis and treatment, attitudes of healthcare providers toward cancer services, information available to patients, and patients' views on enhancing future care. Results: A total of 29 responses were received from women ranging in age from 26 - 74 years. Despite generally positive feedback on the care received (42% as excellent/very good, 55% as good/acceptable, and only 3% as bad), these women identified areas for improvement. Regarding their personal experience receiving information about their diagnosis and treatment, 86% reported receiving medical attention that helped them cope with their illness and 80% reported being convinced that the medical team was highly qualified and coordinated. However, only 55% of physicians and 44% of nursing staff displayed interest in the patients' goals and wishes after they received their diagnosis. Regarding the attitudes of healthcare providers in cancer services, 62% of the women believed that they should be more empathetic, 65% would like to see the same doctor/nurse/specialist on every visit, and 69% indicated that they would like them to show more interest in the challenges they face on a day-to-day basis. Table 1 summarizes the information that these women would like to receive about their treatment. Conclusions: In conclusion, this study provides insight into the experiences and unmet needs of women living with mBC in Mexico. While the care received by the women was generally positive, the study highlights the need for improvement in certain areas to address their unmet needs. The findings can be used to enhance the standard of care for women with mBC. [Table: see text]

MELODY (Methods for Localization of Different Types of Breast Lesions): A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).

TPS626 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com ). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 20 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Clinical trial information: NCT05559411 .

Abstract P4-07-62: Real-World, Single-Center Experience on the Outcomes of Neoadjuvant Chemotherapy and Trastuzumab alone or in Combination with Pertuzumab in Human Epidermal Growth Factor Receptor 2 Breast Cancer Patients

Abstract Background: Neoadjuvant chemotherapy is the standard of care for early stage breast cancer. Human epidermal growth factor receptor 2 (HER2) positive disease constitutes a large proportion of breast cancer patients, and HER2 overexpression is associated with poor prognosis. The induction of HER2+ targeted therapies, such as trastuzumab and pertuzumab, has resulted in improved outcomes in HER2+ breast cancers. Neoadjuvant chemotherapy in combination with HER2 targeted therapies aims at achieving pathological complete response (pCR) and an improved survival. Methods: We performed a retrospective review of HER2+ breast cancer patients who were treated at Medanta – The Medicity Hospital, Gurugram, Haryana, India, between 2011 and 2021. A total of 108 HER2+ breast cancer patients who received neoadjuvant chemotherapy with platinum, anthracycline or taxane-based regimens, along with trastuzumab alone or in combination with pertuzumab, were included. Results: Of 108 enrolled patients, 66 and 42 patients received single-blockade (trastuzumab) and dual-blockade (trastuzumab and pertuzumab) neoadjuvant anti-HER2 therapy, respectively. The majority of patients were aged &amp;lt; 60 years. The patient populations were comparable in terms of clinical stage, hormone receptor status, histopathology category (IDC being most common) and Ki67 status for single- and dual-blockade groups. All patients had IHC3+/FISH+ HER2 expression. No significant (p=0.896) difference was observed for breast conserving surgery between the groups. A higher pCR rate after surgery was reported in the dual-blockade group versus single-blockade group (50% vs. 39.2%; p=0.271). The median follow-up duration was 21.9 and 15.2 months in the single-blockade and dual-blockade groups, respectively. For dual- vs. single- blockade groups, the 1-year OS rates were 100% vs. 100%, and 3-year OS rates were 100% vs. 98.48%. For dual- vs. single- blockade groups, the 1-year DFS rates were 100% vs. 95.45%, and 3-year DFS rates were 92.85% vs. 80.3%. Conclusion: Neoadjuvant chemotherapy with dual HER2-blockade had higher pCR and survival rates compared with the single HER2-blockade strategy in HER2 positive breast cancer. Table. Patient characteristics BCS, breast conserving surgery; ER, estrogen receptor; PR, progesterone receptor; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma. Citation Format: Ashok K. Vaid, Devender Sharma, Jyoti Wadhwa, Rajeev Agarwal, Kanchan Kaur, Shina Goyal, Dheeraj Gautam, Jyoti Arora, Sabhyata Gupta, Ashok Sen, Ruchika K. Goel, Shagun Mahajan. Real-World, Single-Center Experience on the Outcomes of Neoadjuvant Chemotherapy and Trastuzumab alone or in Combination with Pertuzumab in Human Epidermal Growth Factor Receptor 2 Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-62.

Is there an Association of Glycosylated Haemoglobin A1c and Anthropometric Measurements in Premenopausal and Postmenopausal Breast Cancer Patients?

Background: Breast cancer is the commonest malignancy among women globally. It is a leading cause of cancer death in less developed countries and the second leading cause of cancer death in developed countries. Diabetes and breast cancer are two conditions that frequently coexist, and menopause may be a metabolic watershed. The purpose of this study is to examine the relationship between glycosylated haemoglobin (HbA1c) and anthropometric measurements in premenopausal and postmenopausal breast cancer patients Methods: 100 patients diagnosed with breast cancer between December 2020 to November 2022 were evaluated and their HbA1c levels were correlated with anthropometric measurements and tumour characteristics Results: In our study mean age of the patients was 47.75 ±11.77 SD years. In patients with normal HbA1c 64% patients were pre-menopausal. In Pre-diabetic HbA1c group 70% were post-menopausal and in diabetic HbA1c group 93% were postmenopausal. Mean waist circumference was 84.56 ± 6.64 SD cms; more in pre-diabetic and diabetic patients; (p value 0.000). Most of the patients (71%) had waist to hip ratio ≥0.85 (p value 0.349). Pre-diabetic and diabetic patients were overweight (p value 0.000). 6 patients were known cases of type II diabetes mellitus and were on insulin/OHAs. T3 tumours were more common in both premenopausal and postmenopausal patients followed by T4 tumours. Stage IIB breast cancer was present in 39% of premenopausal and stage IIIA was seen in 30% of the postmenopausal patients. Grade II disease was more common in both premenopausal and postmenopausal (p value 0.858). Invasive ductal carcinoma-No special type (IDC-NST) was seen in 77% of the patients (p value 0.156). Estrogen Receptor (ER) positivity was seen in 42% of premenopausal and 33% of postmenopausal patients, negative Progesterone Receptor (PR) seen in 86% in premenopausal and 89% in postmenopausal patients and positive Her2 neu receptor was observed in 30% in premenopausal and 56% in postmenopausal patients. Conclusion: Our study demonstrated that a considerable proportion of breast cancer patients were prediabetic. Glycaemic status and HbA1c were clearly associated with measures of visceral obesity in carcinoma of breast patients. Postmenopausal patients had higher levels of HbA1c compared to premenopausal cases. However; clinicopathological and tumour characteristics in our study didn’t demonstrate any significant correlation with glycaemic status and need more research and randomized controlled trials. Collectively, findings from our study particularly emphasize the need to control hyperglycemia and identify vulnerable groups of breast cancer patients who might benefit from interventions to improve glycaemic control.

Risk factors for heightened COVID-19-Related anxiety among breast cancer patients.

BackgroundThe COVID‐19 pandemic has disrupted medical care, increased isolation, and exacerbated anxiety in breast cancer patients. Since March 2020, Breastcancer.org experienced a sustained surge in requested pandemic‐related information and support. To characterize the pandemic‐related experiences of breast cancer patients, we surveyed the Breastcancer.org Community early in the COVID‐19 era.Methods Breastcancer.org Community members were invited to complete an online questionnaire regarding their experience during the pandemic. Self‐reported data on demographics, comorbidities, care disruptions, anxiety, coping ability, telemedicine use, and satisfaction with care were collected. Results were analyzed using Stata 16.0 (Stata Corp., Inc).ResultsIncluded were 568 current and previous breast cancer patients, primarily with U.S. residence. Overall, 43.8% reported at least one comorbidity associated with severe COVID‐19 illness and 61.9% experienced care delays. Moderate to extreme anxiety about contracting COVID‐19 was reported by 36.5%, increasing with number of comorbidities (33.0% vs. 55.4%, p = 0.021), current breast cancer diagnosis (30.4% vs. 42.5%, p = 0.011), and poorer coping ability (15.5% vs. 53.9%, p < 0.0001). Moderate to extreme anxiety about cancer care disruptions was reported by 29.1%, increasing with current breast cancer diagnosis (19.1% vs. 38.9%, p < 0.0001), actual delayed care (18.9% vs. 35.3%, p < 0.0001), and poorer coping ability (13.1% vs. 57.7%, p < 0.0001). Most utilized telehealth and found it helpful, but also expressed increased anxiety and subjectively expressed that these were less preferable.ConclusionEarly in the COVID‐19 pandemic, anxiety was reported by a large proportion of breast cancer patients, with increased prevalence in those with risk factors. Attention to mental health is critical, as emotional distress not only harms quality of life but may also compromise outcomes.

Radiomic Signatures for Predicting Receptor Status in Breast Cancer Brain Metastases.

BackgroundsA significant proportion of breast cancer patients showed receptor discordance between primary cancers and breast cancer brain metastases (BCBM), which significantly affected therapeutic decision-making. But it was not always feasible to obtain BCBM tissues. The aim of the present study was to analyze the receptor status of primary breast cancer and matched brain metastases and establish radiomic signatures to predict the receptor status of BCBM.MethodsThe receptor status of 80 matched primary breast cancers and resected brain metastases were retrospectively analyzed. Radiomic features were extracted using preoperative brain MRI (contrast-enhanced T1-weighted imaging, T2-weighted imaging, T2 fluid-attenuated inversion recovery, and combinations of these sequences) collected from 68 patients (45 and 23 for training and test sets, respectively) with BCBM excision. Using least absolute shrinkage selection operator and logistic regression model, the machine learning-based radiomic signatures were constructed to predict the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of BCBM.ResultsDiscordance between the primary cancer and BCBM was found in 51.3% of patients, with 27.5%, 27.5%, and 5.0% discordance for ER, PR, and HER2, respectively. Loss of receptor expression was more common (33.8%) than gain (18.8%). The radiomic signatures built using combination sequences had the best performance in the training and test sets. The combination model yielded AUCs of 0.89, 0.88, and 0.87, classification sensitivities of 71.4%, 90%, and 87.5%, specificities of 81.2%, 76.9%, and 71.4%, and accuracies of 78.3%, 82.6%, and 82.6% for ER, PR, and HER2, respectively, in the test set.ConclusionsReceptor conversion in BCBM was common, and radiomic signatures show potential for noninvasively predicting BCBM receptor status.

Impact of the COVID-19 Pandemic on Radiotherapy Patterns of Practice for Curative Intent Breast Cancer Patients

Purpose/Objective(s)In response to the COVID-19 pandemic, radiotherapy (RT) departments around the world created new policies as a means of reducing risk of exposure for patients and staff, while attempting to maintain high-quality RT. We aim to describe the impact of the pandemic on changes in breast cancer RT patterns of practice for new patient referrals at a tertiary cancer center.Materials/MethodsNewly diagnosed breast cancer patients referred to our department from March 17-June 30, 2020 were included. Referrals for palliative RT were excluded. Demographic characteristics, COVID-19 status (if available) and RT treatment information, including deviations from usual practice because of the pandemic, were extracted from medical records by independent reviewers, and validated by the treating radiation oncologist. Descriptive statistics were used to summarize the data. The results were compared to breast cancer patients treated from March 17-June 30, 2019.ResultsA total of 271 and 306 patients met selection criteria for the 2020 and 2019 cohorts, respectively. The majority of consultations in 2020 were virtual (96%), conducted via telephone or videoconference, whereas in 2019 all were conducted in-person. Median age of the cohorts was similar: 58 years (range: 24-86) in 2020 and 59 years (range: 26-88) in 2019. Of those treated with adjuvant RT (n = 209), 56% of patients received whole breast (WB), 36% regional nodal irradiation (RNI) and 8% partial breast (PB) RT in 2020, whereas in 2019 (n = 284), 60% received WB, 31% RNI and 9% PB (Chi-squared test P = 0.43). As a result of the pandemic, 78% of cases (n = 211) received one or more deviations in RT practice compared to pre-pandemic institutional policies. The most common was an “altered dose/fractionation protocol” (n = 197; 93%), such as use of hypofractionated RNI (2020: 97%, 74/76 cases vs. 2019: 3%, 3/87 cases) or the FAST Forward regimen (2020: 43%, 57/134 WB/PB cases vs. 2019: 0/197 cases). Other deviations included a delay in RT start (defined as > 12 weeks post-op) noted in 11% (n = 29) and omission of RT in only 8% (n = 17), both were recommended when the risks associated with COVID-19 were felt to outweigh the benefit of RT. One patient had a deviation in RT as a result of testing positive for COVID-19.ConclusionIn order to minimize hospital visits in response to the COVID-19 pandemic, a substantial proportion of breast cancer patients were seen virtually and treated with newer hypofractionated dose schedules, while total omission of adjuvant RT was infrequently observed. Continuously tracking patterns of practice provides an opportunity to evaluate the impact of the pandemic on clinical outcomes and help inform post-pandemic value-enhancing practices.

Prevalence of HER2 low in breast cancer subtypes using the VENTANA anti-HER2/neu (4B5) assay.

1021 Background: Breast cancer patients with HER2 low expression by immunohistochemistry (IHC), defined as IHC1+ or IHC2+ without gene amplification (ISH-) do not respond to conventional anti-HER2 therapies such as trastuzumab or pertuzumab. The HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) showed efficacy in late line HER2-overexpressing patients, with some responses in patients with low HER2 expression. Two of the market leading IHC IVDs are Dako Herceptest and Ventana 4B5. T-DXd is being investigated in HER2 low patients as determined by the VENTANA anti-HER2/neu (4B5) assay in the phase III DESTINY-Breast04 study. There is a paucity of information on prevalence of IHC1+/2+ in different breast cancer subtypes, which this study aims to address. Methods: HER2 status was calculated from 3750 consecutive primary or metastatic breast cancer patient samples successfully stained using the 4B5 assay and scored locally according to ASCO/CAP 2018 guidelines. Samples were obtained from 3 anatomic pathology labs that support networks of US community hospitals. 500 additional breast cancer samples, pre-selected to include a range of IHC staining (concordance cohort), were stained with both 4B5 and HercepTest (Dako/Agilent) and scored (IHC0, IHC1+, IHC2+, IHC3+) at a central laboratory. Results: Prevalence of HER2 categories in 3750 consecutive breast cancer samples is presented in the table below. &gt;50% of estrogen-receptor positive (ER+ve) and progesterone receptor positive (PR+ve) subtypes are HER2 low. In the 500 sample concordance cohort, 28.0% were IHC1+/2+ using the 4B5 assay compared with 11.6% using HercepTest. HercepTest identified IHC1+/2+ staining in 21.6% [95%CI:15.1,29.4] of the patients classified as IHC1+/2+ by 4B5. 98.3% [95%CI: 96.2, 99.5] of samples IHC0 by 4B5 were also IHC0 by Herceptest. Conclusions: HER2 IHC1+/2+ (ISH-) by Ventana 4B5 represent a significant proportion of breast cancer patients and more than 50% of ER+ve and PR+ve subtypes. The 4B5 assay classed several patients as IHC1+/2+ that are IHC0 by Herceptest, but almost all patients IHC0 by 4B5 were also IHC0 by Herceptest.[Table: see text]

Screening of Human Epidermal Growth Factor Receptor 2 (HER2) Extracellular Domain for Potential Epitopes by Using Immuno-informatics Tools

The human epidermal growth factor receptor 2 (HER2) is a well-studied oncoprotein that is overexpressed in a considerable proportion of breast cancer patients. The increased expression of this tyrosine kinase receptor is usually associated with poor clinical prognosis in female patients with breast cancer. In these patients, specific response of immune system against HER2 had been observed. This suggests that immunotherapy approaches can be employed for enhancing the response of tumor infiltrating lymphocytes against HER2 in susceptible tumor microenvironment. In this regard, peptide vaccines are considered one of the most affordable immunotherapy modalities due to their low production cost and long-term effect. For this purpose, we have screened the extracellular domain of HER2 crystal for potential B-cells and T-cells epitopes by using different immuno-informatics tools. The output peptides were then refined and filtered according to their antigenicity, allergenicity and vulnerability to selected proteases. Here, we present multiple B-cells and T-cells epitope candidates against HER2 extracellular domain with high antigenicity, low allergenicity and good resistance for selected proteolytic enzymes. These filtered epitopes can be used for design and construction of anti-HER2 peptide vaccine for potential use in HER2 positive breast cancer patients. Additionally, the sequence of linear B-cells epitopes can be used for the design of monoclonal antibody variable region against HER2 extracellular domain.

Impact of post-diagnosis weight change on survival outcomes in Black and White breast cancer patients

PurposeTo evaluate weight change patterns over time following the diagnosis of breast cancer and to examine the association of post-diagnosis weight change and survival outcomes in Black and White patients.MethodsThe study included 2888 women diagnosed with non-metastatic breast cancer in 2000–2017 in Chicago. Longitudinal repeated measures of weight and height were collected, along with a questionnaire survey including questions on body size. Multilevel mixed-effects models were used to examine changes in body mass index (BMI). Delayed entry Cox proportional hazards models were used to investigate the impacts of changing slope of BMI on survival outcomes.ResultsAt diagnosis, most patients were overweight or obese with a mean BMI of 27.5 kg/m2 and 31.5 kg/m2 for Blacks and Whites, respectively. Notably, about 45% of the patients had cachexia before death and substantial weight loss started about 30 months before death. In multivariable-adjusted analyses, compared to stable weight, BMI loss (> 0.5 kg/m2/year) showed greater than 2-fold increased risk in overall survival (hazard ratio [HR] = 2.60, 95% CI 1.88–3.59), breast cancer-specific survival (HR = 3.05, 95% CI 1.91–4.86), and disease-free survival (HR = 2.12, 95% CI 1.52–2.96). The associations were not modified by race, age at diagnosis, and pre-diagnostic weight. BMI gain (> 0.5 kg/m2/year) was also related to worse survival, but the effect was weak (HR = 1.60, 95% CI 1.10–2.33 for overall survival).ConclusionBMI loss is a strong predictor of worse breast cancer outcomes. Growing prevalence of obesity may hide diagnosis of cancer cachexia, which can occur in a large proportion of breast cancer patients long before death.

Impact of 18F-FDG PET, PET/CT, and PET/MRI on Staging and Management as an Initial Staging Modality in Breast Cancer: A Systematic Review and Meta-analysis.

We performed a systematic review and meta-analysis to evaluate the impact of 18F-FDG PET, PET/CT, and PET/MRI on staging and management during the initial staging of breast cancer. We searched the PubMed, Embase, Cochrane Library, and KoreaMed databases until March 2020 to identify studies that reported the proportion of breast cancer patients whose clinical stage or management were changed after PET scans. The proportion of changes was pooled using a random-effects model. Subgroup and metaregression analyses were performed to explore heterogeneity. We included 29 studies (4276 patients). The pooled proportions of changes in stage and management were 25% (95% confidence interval [CI], 21%-30%) and 18% (95% CI, 14%-23%), respectively. When stage changes were stratified according to initial stage, the pooled proportions were 11% (95% CI, 3%-22%) in stage I, 20% (95% CI, 16%-24%) in stage II, and 34% (95% CI, 27%-42%) in stage III. The relative proportions of intermodality and intention-to-treat changes were 74% and 70%, respectively. Using metaregression analyses, the mean age and the proportion of initial stage III to IV and histologic grade II to III were significant factors affecting the heterogeneity in changes in stage or management. Currently available literature suggests that the use of 18F-FDG PET, PET/CT, or PET/MRI leads to significant modification of staging and treatment in newly diagnosed breast cancer patients. Therefore, there may be a role for routine clinical use of PET imaging for the initial staging of breast cancer.

Women who undergo mastectomy for breast cancer are now offered reconstruction in line with national guidelines but the majority decline: A UK teaching hospital experience.

The aim of this study was to evaluate what proportion of breast cancer patients were offered reconstruction following mastectomy (to assess compliance with national guidelines) and to consider the reasoning if patients were not given this option. Records of all mastectomies were obtained from a prospectively maintained database (September 2018-October 2019). The following were collected: demographics, indication for surgery, tumour properties, and indication for mastectomy over breast-conserving surgery. Clinic letters were used to determine whether patients were offered reconstruction and whether they accepted. If a patient was not offered reconstruction, the rationale for this was recorded. 201 mastectomies were carried out on 179 patients. 77.3% of women were offered reconstruction following mastectomy for cancer and 92.9% of women were offered reconstruction following mastectomy for non-invasive disease. Patients were not offered reconstruction only if they had significant co-morbidities (ASA grade III or higher); no patients who expressed an interest in reconstruction were declined. The most common reasons reconstruction was not offered included: deemed too frail following surgeon assessment (29.7%), advanced cancer (16.2%), and deemed high-risk following anaesthetist assessment (16.2%). 59.1% of patients who were offered reconstruction declined. Mean age in those who declined was significantly higher (P > 0.001). Our unit now complies with national guidelines when offering reconstruction to mastectomy patients; this service was not previously offered. Further research into the reasons behind why women are declining reconstruction is necessary to ensure we are providing adequate information in an appropriate format.