bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the mental health of South African women living with comorbid HIV and breast cancer.
Authors: O'Neil Daniel , Blanchard Charmaine , Joffe Maureen , Ream Molly , Tshabalala Gugulethu , Diaz Alain , Chen Wenlong Carl , Mkwanazi Nontlantla , Blomberg Bonnie , Antoni Michael 
Published: June 2023

e12549 Background: In South Africa’s public hospitals, 20% of new breast cancer (BC) diagnoses are in women living with HIV (WLWH). These women experience 49% higher mortality than BC patients without HIV. Mental health disorders are prevalent in both WLWH and women with BC. Symptoms of depression, anxiety, and acute stress are linked to increased circulating serum inflammatory markers, which may provide a pathophysiologic explanation for poorer outcomes. We aimed to explore whether South African BC patients living with HIV report more mental health symptoms than women with HIV alone, BC alone, or neither and to determine if comorbid HIV and BC is associated with greater systemic inflammation. Methods: We conducted a cross-sectional study of black South African women ≥18 years old. We enrolled four arms: newly diagnosed BC patients with HIV, newly diagnosed BC patients without HIV, WLWH without BC, and women with benign breast diagnoses. Participants were recruited from the breast clinic or HIV clinic at Chris Hani Baragwanath Academic Hospital. Consenting women completed the Center for Epidemiologic Studies Depression Scale (CES-D), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Perceived Stress Scale (PSS). Blood samples were tested for serum concentrations of inflammatory markers (c-reactive protein (CRP) and S100A8/A9), pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), and anti-inflammatory cytokines (IL-4, IL-5, and IL-10) via ELISA assays performed at the University of Miami. Results: The first three arms enrolled 25 women each and the benign arm enrolled 22 women. Participant scores on the CES-D, GAD-7, and PSS were higher than expected in all groups and seemed to be worse in participants with HIV alone. Scores consistent with clinical depression, moderate to severe anxiety, and moderate to severe stress were reported by 68-88%, 28-76%, and 72-94% of participants, respectively. We found trends towards higher concentrations of CRP, TNF-α, IL-6, and IL-8 in participants with co-morbid BC and HIV versus benign breast disease but no pattern of increased inflammatory marker concentrations in participants with dual diagnoses versus either diagnosis alone. Conclusions: Our pilot study did not find evidence of increased mental health symptom burden or systemic inflammation in South African women with comorbid breast cancer and HIV, versus either diagnosis alone. Increased mental health symptoms in women with HIV alone may reflect reduced access to supportive service available at the HIV clinic compared to the breast clinic. [Table: see text]
Fatty acid desaturase activity and single nucleotide polymorphism of fatty acid desaturase gene and breast cancer risk in estrogen receptor subtype.
Authors: Sonkusare Shipra 
Published: June 2023

e12551 Background: Breast cancer (BC) is the most common cancer in women. Various mechanisms are known to promote tumourogenesis. Arachidonic acid and its metabolites are one such pathway which promote tumorigenesis by inflammation and angiogenesis. It can be hypothesized that fatty acid metabolism is dysregulated in women with BC. We compared the fatty acid desaturases activity in women with BC and the control women. Breast cancer, which is a diet-related inflammatory disease, is also associated with the plasma concentration of omega fatty acids (n-3 and n-6), and can have an impact of its genetic variants. We studied the association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and the estrogen receptor positive BC. Methods: Sixty women diagnosed with BC and 40 control women without BC between the age group of 25-60years of age were recruited for comparing the fatty acid desaturases activity. The tumors were classified by Estrogen Receptor (ER) status. Fatty acid Desaturases activities (D5, D6 and D9) were estimated as the ratio of product to precursor of individual fatty acids in plasma lipids. To study the association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and the estrogen receptor positive BC, we recruited 102 (ER +ve, n = 53; ER -ve,n = 49) women with proven BC, prior to therapy. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing. Results: Decreased levels of delta 5 and delta 9 desaturases activity and increased delta 6 desaturase activity were associated with the adverse profile of BC than the control group. Estrogen Receptor status also showed variation in desaturase activity. The highest tertile of Alphalinolenic acid (ALA) showed a significantly reduced association with BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1–1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and Docosapentaenoic acid (DPA) was higher in GG genotype of ER -ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced association with BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2–0.9). Conclusions: We conclude that unbalanced polyunsaturated fatty acids and impaired fatty acid desaturation plays a role in the pathogenesis of BC. The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu which might contribute to the pathogenesis of BC. We also conclude that the individuals with genetically determined lower activity of FADS1 (minor allele T) will derive greater advantage from n-3 fatty acids than those with higher FADS1 activity (G allele).
Incidental discovery of second primary malignancies in patients diagnosed with breast cancer: An institutional case series.
Authors: Iancu Alexandra , Manohar Poorni , Vinayak Shaveta , Gwin William R. , Linden Hannah M. , Specht Jennifer M. , Symonds Lynn Katherine , Davidson Nancy E. , Hunter Natasha 
Published: June 2023

e12552 Background: National guidelines recommend tissue biopsy of suspected recurrent breast cancer, to confirm diagnosis and to characterize disease phenotype, receptor status, and molecular markers. Despite this, clinicians frequently rely on imaging alone to diagnose recurrent breast cancer; indeed, our group recently published data revealing that only half of patients in Washington state diagnosed with metastatic breast cancer between 2008 and 2017 underwent confirmatory biopsies for suspected metastatic disease on imaging. Here we present evidence of how this failure to fully evaluate suspected breast cancer recurrence could potentially lead to misdiagnosis. Methods: We surveyed our breast medical oncology faculty to identify patients treated at Fred Hutchinson Cancer Center (FHCC) from 2018 to 2022 in which a second primary carcinoma (not including non-melanoma skin cancers) was discovered as part of breast cancer workup and treatment. Results: We identified 10 cases of second primary diagnoses. Of these, the majority (7/10) were lung cancer; other diagnoses included neuroendocrine tumors (1), chronic lymphocytic leukemia (1), and thyroid cancer (1). In the case of lung cancers, patients were typically diagnosed during staging or CT evaluation for radiation or reconstruction, in which a pulmonary nodule raised suspicion for malignancy. In five cases, patients were treated with curative intent for both of their early-stage primary malignancies, and remain disease-free on endocrine therapy alone. In two cases, patients with biopsy-proven metastatic breast cancer were found to have new suspicious lung lesions, which on biopsy were found to represent lung adenocarcinoma; these patients were treated surgically for their lung cancer and continued long-term therapy for metastatic breast cancer. Conclusions: While imaging can raise strong suspicion for metastatic recurrence of breast cancer, the assumption that an apparently metastatic lesion 1) indeed represents metastasis and 2) represents metastatic spread of the known primary rather than another malignancy, risks treating both the primary tumor and the newly detected condition inappropriately. Biopsy is critical for confirmation of metastatic disease vs second primary or other etiology. As patients with metastatic breast cancer are surviving longer as our cancer-directed therapies improve, appropriate diagnostic measures for a suspicious non-breast malignancy are recommended for optimal care. Novel imaging modalities such as 18F-fluoroestradiol (FES) PET and others could be explored in discriminating between metastatic lesions and unrelated conditions.
In search for new targets: Differences of HER2 receptor expression between CNB and synchronous axillary lymph node metastases in 205 patients.
Authors: Weydandt Laura , Dogan Senol , Nel Ivonne , Horn Lars-Christian , Aktas Bahriye 
Published: June 2023

e12559 Background: Lately large clinical trials have provided new treatment options for patients with metastatic HER2-low breast cancer. Studies have shown that there may be change in the expression of HER2 during disease progression. Yet, it is rarely considered that there can be already differences between primary tumor and synchronous lymph node metastases (LMN) in the primary setting. The aim of the present study was to analyze different HER2 expression profiles between primary tumor and synchronous LNM. Methods: We included 205 patients with primary breast cancer and LNM who underwent oncologic surgery between 2008 and 2021. Formalin-fixed and paraffin-embedded (FFPE) material were routinely examined immunohistochemically according to the ASCO guidelines. Membranous HER2-staining was scored as follows: zero = 0, low = 1+, equivocal = 2+ and positive = 3+. Results: 205 patients were either HER2 low or HER2 zero in CNB. When comparing CNB and LNM 5 (2,4%) patients were HER2 zero in CNB and HER2 low in LNM. 161 (78.5%) patients were HER2 zero in both CNB and LNM. 21 (10.2%) patients had a shift from HER2 low to HER2 zero in LNM. 18 (8,8%) patients had a HER2 low expression in CNB and HER2 zero expression in LNM. Conclusions: There seems to be a high frequency of HER2 heterogeneity between primary tumor and LNM in the primary setting. Different HER2 expression profiles should be considered for an optimal and individual treatment.
Prevalence and patterns of breast white adipose tissue inflammation among American Black women and indigenous Nigerian women with early-stage breast cancer.
Authors: Liu Bethina , Shen Sherry , Omoyiola Oluwatosin Zainab , Odujoko Oluwole O. , Sharma Avinash , Ogunleye Gbenga Samson , Owoade Israel Adeyemi , Olasehinde Olalekan , Wuraola Funmilola Olanike , Ntiamoah Peter , Flynn Jessica , Chen Yuan , Giri Dilip D. , Carpio Andrea , Kahn Rivka , Chang Cassandra , Morrow Monica , Alatise Olusegun Isaac , Kingham T. Peter , Iyengar Neil M. 
Published: June 2023

e12560 Background: Racial disparities in breast cancer outcomes pose a major public health challenge. Complex interactions between social determinants of health and tumor biology, mediated by obesity and adiposity, may play an important role in these disparities. White adipose tissue inflammation (WATi) of the breast, which is histologically defined by the presence of crown-like structures (CLS-B), occurs in the setting of excess adiposity and promotes tumor growth via elevated levels of aromatase, proinflammatory growth factors, and metabolic dysregulation. Here we examined relationships between race, body mass index (BMI), and WATi in two cohorts of patients with early-stage breast cancer: 1) American Black women and 2) indigenous Nigerian women. Methods: Non-tumor breast WAT specimens were collected from patients undergoing mastectomy for treatment or prevention of breast cancer at Memorial Sloan Kettering Cancer Center (MSK) in the US and Obafemi Awolowo University Teaching Hospital (OAUTH) in Nigeria. WATi was defined by the presence of CLS-B as detected by CD68 immunostaining. All tissue analyses were performed at MSK. Associations among BMI and WATi were tested within each cohort using Kendall’s tau rank correlation and compared between cohorts using Pearson's Chi-squared test. Results: A total of 224 American women were enrolled at MSK between 2011-2018, of whom 39 self-reported Black race. At OAUTH, 97 Nigerian women were enrolled between 2018-2022. Invasive carcinoma was present in 32 American Blacks and 97 Nigerians. Of those with invasive carcinoma, the prevalence of WATi among American Black women was 72% vs. 37% in the Nigerian cohort ( p<0.001). In the US cohort, there was no significant difference between the prevalence of WATi among Black vs. non-Black patients (72% vs. 62%; p=0.3). 44% of American Blacks were obese and 34% overweight compared with 27% and 39% of Nigerians, respectively (p=0.07). The prevalence of WATi varied by BMI category within each cohort, as shown. Overweight/obesity was associated with WATi in the Nigerian (p=0.009) and American cohorts (p<0.001); a trend was observed in the American Black subgroup (p=0.13). Conclusions: Breast WATi and obesity were more prevalent among American Black women with breast cancer compared with Nigerian women. These findings highlight the need for further investigation of environment, lifestyle patterns, and body composition differences between indigenous and diaspora populations. [Table: see text]
Clinical subtypes and survival outcomes in invasive breast cancer with Paget’s disease: A SEER population-based study.
Authors: Bae Soo Youn , Lee Ji Eun , Park Woo-Chan , Yoon Chang Ik , Kim Dooreh , Shin Kabsoo , Lee Youngjoo 
Published: June 2023

e12564 Background: The objective of this study was to investigate the clinicopathological characteristics, especially subtypes and survival outcomes of Invasive breast cancer with Paget's disease. Methods: 4930 patients were identified using the histopathology codes from the International Classification of Disease for Oncology third edition (ICD-O-3), from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. Excluding 787 patients whose ICD-O-3 and TNM stages did not match, there were 663 patients with '8540/3, Paget disease, mammary', 976 patients with ‘8543/3, Paget disease and intraductal carcinoma(DCIS)’ and 2540 patients with ‘8541/3, and ‘8541/3, Paget disease and infiltrating ductal carcinoma (IDC) of breast’. ER and PR status have been available since 1990, and HER2 status since 2010. Results: Among patients with IDC and Paget's disease, 24.6% were under the age of 50 and 2.7% were male, which was higher than the other two groups. Expressions of ER and PR were higher than both groups, and HER2 expression was lower. The ratio of HR-/HER2+ subtype was also lower than the other two groups at 29.6%. ER+, Paget 43.7%, DCIS with Paget 36.4%, IDC with Paget 53.6%. PR+ Paget 21.6%, DCIS with Paget 21.7%, IDC with Paget 40.1%. HER2+ Paget 69.2%, DCIS with Paget 83.1 %, IDC with Paget 58.3%. HR-/HER2+subtype, Paget 40.7%, DCIS with Paget 49.2%, IDC with Paget 29.6%. As a result of survival analysis in patients with IDC and Paget's disease, the HR-/HER2+ subtype had shown the best prognosis in Overall Survival (OS) analysis (5year OS, HR+/HER2- 70.8%, HR+/HER2+ 74.9%, HR-/HER2- 63.7%, HR-/HER2+ 80.7% P=0.010) In the BCSS analysis, the 5-year BCSS was the best at 87.0% in the HR-HER2+ subtype, but there was no statistically significant difference. Conclusions: In IDC with Paget's disease, the distribution of subtypes is different from that of DCIS with Paget's, and HER2 expression can be considered as a favor prognostic factor. It is considered necessary to study the relationship between the loss of HER2 overexpression and invasion/progression in invasive breast cancer with Paget's disease.
Are we using the right cut-offs to obtain maximum information from Ki-67 in patients with early breast cancer?
Authors: Trifanescu Oana Gabriela , Bilteanu Liviu , Ilie Silvia , Bran Diana Maria , Safta Inga , Gales Laurentia Minea , Anghel Rodica Maricela 
Published: June 2023

e12567 Background: Ki-67 is one of the most critical prognostic proliferation markers in breast cancer, used on a large scale by oncologists to select treatment options. This study aimed to validate Ki-67 as a prognostic marker and establish the optimal Ki67 cut-offs for stratifying patient prognosis and treatment decisions. Methods: Medical files of 582 consecutive patients with early breast cancer (stage IB-IIIA) who underwent surgery as a first treatment in our institution between 2005-2019 were retrospectively reviewed. Values of Ki-67 were divided into 5 categories: 0-9%, 10-19%, 20-29%, 30-39%, and more than 40%. Results: Kolmogorov-Smirnov and Shapiro-Wilk tests showed that the patient’s age (yrs) at diagnostic, Ki-67 (in %), tumor size (in mm), estrogen and progesterone receptors abundance (%), exhibit normal distributions (p < 0.05). Median age at diagnosis was 54.8 (± 11.5) years and mean Ki-67 of 25.5 ± 16.5 and a median value of 20. Stage distribution was: stage IB 5.5%, IC 12%, IIA 46.6%, IIB 20.4%, IIIA 15.5%. The mean tumor dimension at diagnosis was 21.3 mm. After a median follow-up of 48 months (6-118), estimated disease-free survival rates (DFS) for all patients at 3 and 5 years were 92% and 79%. Disease-free survival rates at 5 years was 96% for patients with Ki-67 0-9%, 90% for patients with Ki-67 10-19%, 80% for patients with Ki-67 20-29%, 75% for patients with Ki-67 30-39%, and 72% for patients with Ki-67 more than 40%. The difference between the median DFS and each ki67 category was statistically significant (p < 0.0001). Using the fit of mixture method, we identify a new cut-off of 29% that negatively predicts DSF for patients (HR = 4.51 95% CI = 1.69-12.04, p = 0.001). Pearson correlation coefficients (p < 0.05) for Ki-67 and DFS, age, ER%, PR%, p53, and tumor size were -0.110, -0.096, -0.139, -0.136, 0.301, and 0.175, respectively. Moreover, DFS was also negatively correlated (p < 0.01) with the patient’s age (-0.106) and tumor size (-0.180). Though the correlation coefficients were small, they oriented the creation of linear models of DFS as a dependent variable and Ki-67, tumor size, and age. DFS has a statistically significant dependence only on the first two variables (standardized coefficients -0.103, p = 0.045 and -0.161, p = 0.02). Conclusions: Ki-67 is a strong prognostic factor in early breast cancer patients. New Ki-67 cut-off levels that may be used in clinical practice were identified. In addition, multivariate analysis showed a significant statistical influence of other factors, such as Ki67 and tumor size. Such correlations can be the basis of a scoring system for progression risk.
Clinicopathological characteristics and outcome of very young breast cancer patients at a referral center in Iran.
Authors: Malekzadeh Moghani Mona , Hashemi Atieh Sadat , Bazgir Narges 
Published: June 2023

e12568 Background: Although breast cancer (BC) is the most common type of cancer in women worldwide, in women younger than 35 years old is uncommon and only accounts for 2% of breast cancer diagnosed in western countries. However, there is insufficient data on breast cancer in women younger than 35 years old in Iran. The aim of this study was to assess clinicopathological parameters in these very young breast cancer patients. Methods: In this retrospective cohort study, we have collected the demographic, clinical and histopathological data of women younger than 35 years diagnosed with BC who presented to our tertiary center from 2011 to 2017. Patients were followed at least for four years and the diseases-free survival (DFS) and overall survival (OS) were assessed. Chi-square and multivariate regression tests were conducted to assess the association of mentioned variables. A P-value less than 0.05 was considered to be statistically significant. Results: A total of 334 women with Breast Cancer younger than 35 years old were included in this study, of which 219 patients were between 31 to 35. The most common histopathologic type was hormone receptor positive, HER2 negative 41.6 %. HER2 positive (regardless of hormone receptor status) and triple negative were 30.1% and 24.6% of cases respectively. Grade1 was reported in 5% of cases, grade 2 and 3 were 50.9 % and 43.6% respectively. 16.9% of patients were presented in stage I, 44.4% stage II, 30.5% stage III and 8.2% had de novo metastatic disease. Of 68 patients who received neoadjuvant chemotherapy, 29.4% had complete pathological response. Sixty five percent of 199 patients with hormone positive had received Luteinizing hormone-releasing hormone (LHRH) agonist, this type of treatment significantly improved 4-year OS regardless of HER2 expression. Mean follow up was 71.5±26.6 months, 4-year DFS and OS were 66% and 80% respectively. Four-year overall survival was analyzed by stage, it was 100% for stage I, 89% stage II, 79% stage III, and 11% stage IV. The four-year OS corresponding to the subtypes was as follows; HR+/HER2- (89.5%), HR+/HER2+ (76.9%), HR-/HER2+ (73.3%) and TNBC (75.4%). Conclusions: Breast cancer occurring in very young women constituted 9.5% of all breast cancer cases treated at Shohada Hospital, Iran, and this high rate shows a significant correlation with unpublished data by Health ministry in 2016-2017. This high percentage is an alarm not only in breast clinics but also in early detection of breast cancer. In according to other published data, clinicopathological subtypes in our center was similar to other papers. The associations of subtypes with stage and grade, were significant.
Incidence of hypomagnesemia in patients with HER2+ breast cancer treated with pertuzumab.
Authors: Shah Nirja , Daily Karen Colleen 
Published: June 2023

e12569 Background: Breast cancer is the most common cancer diagnosed in women. HER2 gene amplification/protein overexpression is seen in about 20% of breast cancer cases. Pertuzumab (P), an EGFR inhibitor, is a monoclonal antibody administered with Trastuzumab in the treatment of HER2-positive breast cancer. Breast oncologists across multiple institutions have noted hypomagnesemia in patients receiving P-containing regimens. Retrospective data from Memorial Sloan Kettering Cancer Center and University of Florida Health have reported the incidence of hypomagnesemia in patients treated with P neoadjuvantly (8/90 and 7/25, respectively). Cetuximab and Panitumumab, also EGFR inhibitors, are well known to cause hypomagnesemia. Hypomagnesemia can be clinically associated with convulsions, atrial tachycardias, hypocalcemia and hypokalemia. This prospective study details the incidence, severity, and timeline of hypomagnesemia in HER2-positive breast cancer patients treated with P. Methods: 27 eligible patients were identified at two institutions through medical oncology clinic visits and weekly tumor board screenings. Inclusion criteria was HER2+ breast cancer patients initiating treatment with P. Patients receiving platinum agents were excluded (8/27). Following informed consent, magnesium levels were obtained along with standard of care comprehensive metabolic panels at the first four P infusions (19/27). Results: A one-sample binomial test was used to compare the proportion of hypomagnesemia at 3 months among subjects who receive P with 2% (historical control). Results demonstrated that only one patient developed a magnesium level below normal range, resulting in no significant difference with historical control (P = 0.291) This patient’s magnesium level was low at baseline and did not significantly improve or worsen throughout treatment with P. Conclusions: There was no significant incidence of hypomagnesemia noted in HER2+ breast cancer patients treated with P. This emphasizes the safety of P in patient populations prone to developing hypomagnesemia such as those receiving concurrent Carboplatin. Our results do not indicate clinical monitoring of hypomagnesemia is necessary for patients receiving P. [Table: see text]