Association between low levels of 1,25-dihydroxyvitamin D and breast cancer risk

AbstractObjectiveTo determine if blood levels of 25-hydroxyvitamin D (25-D) or its active metabolite, 1,25-dihydroxyvitamin D (1,25-D), are lower in women at the time of first diagnosis of breast cancer than in comparable women without breast cancer.DesignThis was a clinic-based case–control study with controls frequency-matched to cases on race, age, clinic and month of blood drawing.SettingUniversity-based breast referral clinics.SubjectsOne hundred and fifty-six women with histologically documented adenocarcinoma of the breast and 184 breast clinic controls.ResultsThere were significant mean differences in 1,25-D levels (pmol ml−1) between breast cancer cases and controls; white cases had lower 1,25-D levels than white controls (mean difference ± SE: −11.08 ± 0.76), and black cases had higher 1,25-D levels than black controls (mean difference ± SE: 4.54 ± 2.14), although the number of black women in the study was small. After adjustment for age, assay batch, month of blood draw, clinic and sample storage time, the odds ratio (95% confidence interval, CI) for lowest relative to highest quartile was 5.2 (95% CI 2.1, 12.8) for white cases and controls. The association in white women was stronger in women above the median age of 54 than in younger women, 4.7 (95% CI 2.1, 10.2) vs. 1.5 (95% CI 0.7, 3.0). There were no case–control differences in 25-D levels in either group.ConclusionsThese data are consistent with a protective effect of 1,25-D for breast cancer in white women.

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Prospective study of pain outcomes associated with contralateral prophylactic mastectomy in women with nonhereditary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6587 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6587-6587

Author(s):

Demetria Joy Smith-Graziani ◽

Patricia A. Parker ◽

Susan K. Peterson ◽

Isabelle Bedrosian ◽

Yu Shen ◽

...

Keyword(s):

Breast Cancer ◽

Black Women ◽

Repeated Measures ◽

White Women ◽

Prophylactic Mastectomy ◽

Contralateral Prophylactic Mastectomy ◽

Mean Difference ◽

Pain Severity ◽

Pain Outcomes ◽

Race Ethnicity

6587 Background: Women with nonhereditary breast cancer are increasingly undergoing contralateral prophylactic mastectomy (CPM). We examined pain severity and the impact of pain on the lives of women who underwent CPM compared to those who did not. We also examined the associations between age, race/ethnicity, reconstruction and pain outcomes. Methods: Between 2012 and 2015, we recruited women with newly diagnosed nonhereditary breast cancer who were planned for surgery. We assessed pain with the Brief Pain Inventory at initial surgical consultation and at 1, 6, 12, and 18 months after surgery. The repeated measures model was used to assess the association between pain severity or interference and CPM status over different time points adjusting for other covariates. Results: Of 288 women enrolled (mean age 56 years, 58% non-Hispanic White, 17% non-Hispanic Black), 50 underwent CPM, 163 had unilateral mastectomy, and 75 had breast conserving surgery. Mean pain severity was higher at 1 month (2.78 vs 1.9, p = .01) and 6 months (2.79 vs 1.96, p = .03) after surgery in women with CPM versus those without. In the multivariable repeated measures model adjusted for time, age, race/ethnicity and reconstruction status, there was a significant interaction between time and CPM for pain severity (p < .01) but not interference (p = .13). This suggests that CPM patients had higher pain severity in the first 6 months after surgery, but their pain scores decreased by 12 months becoming similar to women without CPM. Black women had higher pain severity (mean difference 1.35, standard error [SE] 0.35; p < .01) and interference (mean difference 0.91, SE 0.32; p < .01) compared to White women with or without CPM. There was no association between age or reconstruction status and pain severity or interference. Conclusions: Pain severity in patients undergoing CPM is highest during the first 6 months after surgery. Women considering CPM should be counseled about this potential outcome. Race/ethnic disparities exist in pain management, pain perceptions and communication of pain. Black women undergoing breast surgery report worse pain outcomes than White women regardless of CPM status.

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Distant metastases after diagnosis: Racial disparities in breast cancer outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.1084 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 1084-1084

Author(s):

Julia Blanter ◽

Ilana Ramer ◽

Justina Ray ◽

Emily J. Gallagher ◽

Nina A. Bickell ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Black Women ◽

Racial Disparities ◽

Late Stage ◽

White Women ◽

Univariate Analysis ◽

Distant Metastases ◽

Stage At Diagnosis

1084 Background: Black women diagnosed with breast cancer are more likely to have a poor prognosis, regardless of breast cancer subtype. Despite having a lower incidence rate of breast cancer when compared to white women, black women have the highest breast cancer death rate of all racial and ethnic groups, a characteristic often attributed to late stage at diagnosis. Distant metastases are considered the leading cause of death from breast cancer. We performed a follow up study of women with breast cancer in the Mount Sinai Health System (MSHS) to determine differences in distant metastases rates among black versus white women. Methods: Women were initially recruited as part of an NIH funded cross-sectional study from 2013-2020 to examine the link between insulin resistance (IR) and breast cancer prognosis. Women self-identified as black or white race. Data was collected via retrospective analysis of electronic medical records (EMR) between September 2020-January 2021. Distant metastases at diagnosis was defined as evidence of metastases in a secondary organ (not lymph node). Stage at diagnosis was recorded for all patients. Distant metastases after diagnosis was defined as evidence of metastases at any time after initiation of treatment. Univariate analysis was performed using Fisher’s exact test, multivariate analysis was performed by binary logistic regression, and results expressed as odds ratio (OR) and 95% confidence interval (CI). A p value <0.05 was considered statistically significant. Results: We identified 441 women enrolled in the IR study within the MSHS (340 white women, 101 black women). Median follow up time for all women was 2.95 years (median = 3.12 years for white and 2.51 years for black women (p=0.017)). Among these patients, 11 developed distant metastases after diagnosis: 4 (1.2%) white and 7 (6.9%) black (p=0.004). Multivariate analysis adjusting for age, race and stage at diagnosis revealed that black women were more likely to have distant metastasis (OR 5.8, CI 1.3-25.2), as were younger women (OR for age (years) 0.9, CI 0.9-1.0), and those with more advanced stage at diagnosis. Conclusions: Black women demonstrated a far higher percentage of distant metastases after diagnosis even when accounting for age and stage. These findings suggest that racial disparities still exist in the development of distant metastases, independent from a late-stage diagnosis. The source of existing disparities needs to be further understood and may be found in surveillance, treatment differences, or follow up.

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Geographical disparities of incidence and prevalence of triple-negative breast cancers: Multistate study data analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12599 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12599-e12599

Author(s):

Hyein Jeon ◽

Myeong Lee ◽

Mohammed Jaloudi

Keyword(s):

Breast Cancer ◽

Black Women ◽

Significant Relationship ◽

White Women ◽

Triple Negative ◽

The State ◽

Luminal A ◽

Black Females ◽

Black And White ◽

State Effect

e12599 Background: Higher prevalence of triple negative breast cancer (TNBC) in black women with associated poor outcomes due to various disparities is well documented within a single state. We examine multiple states to better understand the state effect on such differences in incidence and prevalence of TNBC in black women. Methods: Female patients of ages 19 years old and above with breast cancer from the Surveillance, Epidemiology and End Results (SEER) Program across 13 states (608 counties) from 2015 (n = 66,444) and 2016 (n = 66,122) were examined. The relationships between the proportion of black and white women and the rate of patients with different tumor subtypes (luminal A, luminal B, HR-HER2+, and triple negative) were examined at the county level using ordinary least-square regression models. In parallel, due to consideration of various state-specific healthcare policies, socio-cultural norms, and socio-economic disparities, multi-level regression models were applied to examine the nested, random effect of each state on TNBC prevalence in each county. Bonferroni correction was applied to reduce the Type I error caused by repeated use of the same variables in multiple tests. Results: The baseline breast cancer rates between black and white women were similar in the population (0.171% for black and 0.168% for white). Consistent to previous studies, we demonstrate a significant positive correlation (p < 0.001) in TNBC in black females in both years. Surprisingly, when accounted for the random effects on states, 38.2% (2015) and 34.3% (2016) increase in incidence of TNBC in black females were seen, suggestive of state-specific disparity affecting race-specific health. In 2015, other subtypes of breast cancer in both black and white females did not result in significant relationship. Interestingly, in 2016, there was a significant relationship seen between the TNBC rate in white females and the white female population rate only after adjusting for the state effect (p = 0.026). This indicates the impact of non-biological factors such as state-wide health policies. Additionally, HR-HER2+ black females had a significant relationship against respective population rate only after adjusting for the state effect as well (p = 0.0394). For luminal A white females, a 15% decrease in incidence was seen after adjusting for state effect (p = 0.0424). Conclusions: This is the first known across-state examination of breast cancer subtypes by race with random effects on state. This study shows the role of state-specific factors affecting incidence in black and white females and potentially indicates the importance of state-level management for breast cancer on health disparities in addition to race-driven effects. Further studies are needed to elucidate comparable differences between states affecting the rates of various subtypes of breast cancer and thus health outcomes.

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Insulin Resistance and Inflammation in Black Women with and without Breast Cancer: Cause for Concern

Ethnicity & Disease ◽

10.18865/ed.26.4.513 ◽

2016 ◽

Vol 26 (4) ◽

pp. 513 ◽

Cited By ~ 2

Author(s):

Kathleen A. Griffith ◽

Seon Yoon Chung ◽

Shijun Zhu ◽

Alice S. Ryan

Keyword(s):

Breast Cancer ◽

Insulin Resistance ◽

Black Women ◽

White Women ◽

Cancer Recurrence ◽

Control Group ◽

Study Objective ◽

Increased Risk ◽

Tnf Α ◽

History Of

Objective: After chemotherapy for breast cancer, Black women gain more weight and have an increased mortality rate compared with White women. Our study objective was to compare biomarkers associated with obesity in Black women with and without a history of breast cancer.Design: Case-controlSetting: Academic/federal institutionParticipants: Black women with a history of breast cancer (cases) and age-matched controls.Methods: We compared insulin resistance, inflammation, and lipids in overweight and obese Black women with a history of breast cancer (n=19), age similar controls (n=25), and older controls (n=32). Groups did not differ on mean body mass index (BMI), which was 35.4 kg/m2, 36.0 kg/m2, and 33.0 kg/m2, respectively.Main Outcome Measures: Insulin resistance (HOMA-IR); inflammation (TNF-α, IL-1b, IL-6, IL-8, CRP); lipids (cholesterol, triglycerides).Results: Cases had 1.6 and 1.38 times higher HOMA-IR values compared with age similar and older controls, respectively (P≤.001 for both). TNF-α and IL-1b were significantly higher in cases compared with both control groups (P<.001 for both). IL-6 was also higher in cases compared with age-similar controls (P=.007), and IL-8 was lower in cases compared with older controls (P<.05). Lipids did not differ between cases and either control group.Conclusions: Black women with breast cancer were significantly more insulin resistant with increased inflammation compared not only with age similar controls but with women who were, on average, a decade older. These biomarkers of insulin resistance and inflammation may be associated with increased risk of breast cancer recurrence and require ongoing evaluation, especially given the relatively abnormal findings compared with the controls in this underserved group. Ethn Dis. 2016;26(4):513-520; doi:10.18865/ed.26.4.513

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Lifetime Recreational Exercise Activity and Breast Cancer Risk Among Black Women and White Women

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/dji374 ◽

2005 ◽

Vol 97 (22) ◽

pp. 1671-1679 ◽

Cited By ~ 116

Author(s):

Leslie Bernstein ◽

Alpa V. Patel ◽

Giske Ursin ◽

Jane Sullivan-Halley ◽

Michael F. Press ◽

...

Keyword(s):

Breast Cancer ◽

Black Women ◽

Breast Cancer Risk ◽

Cancer Risk ◽

White Women ◽

Recreational Exercise ◽

Exercise Activity

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Investigating survivin as a novel target in black women with breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.594 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 594-594

Author(s):

Andrea Walens ◽

Linnea T Olsson ◽

Sarah Van Alsten ◽

Lisa A. Carey ◽

Melissa A. Troester ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Black Women ◽

White Women ◽

Tumor Biology ◽

Survivin Expression ◽

Breast Tumors ◽

The Cancer Genome Atlas ◽

Molecular Features ◽

Apoptosis Protein

594 Background: Black women with breast cancer have higher mortality than White women. Differences in tumor biology contribute to racial disparities in breast cancer outcomes. BIRC5 gene encodes survivin, an inhibitor of apoptosis protein, and an independent marker of poor prognosis in breast cancer. Cancer patients have anti-survivin antibodies and circulating survivin-specific T cells, suggesting that survivin may be targetable. Several ongoing antibody-mediated, vaccine strategies that target survivin are being developed. Nevertheless, most survivin studies were conducted in cohorts of White women. To date, the prevalence and/or role of survivin expression in breast tumors from Black women has not been studied. Methods: Associations between BIRC5 expression, clinicopathological and molecular features were measured in the population-based Carolina Breast Cancer Study (CBCS) and The Cancer Genome Atlas (TCGA) breast cancer cohort. Gene expression was measured by Nanostring RNA counting and split into BIRC5 high (4th quartile) and low categories based on log2 gene expression values. Relative frequency differences (RFD) for the association between BIRC5 high and clinicopathologic features were estimated. RNA based p53 mutant status and homologous recombination deficiency (HRD) status were included in RFD analysis. Receiver operating characteristic (ROC) curves were used to illustrate the potential of BIRC5 expression to distinguish patients who achieved pathological complete response (pCR) after receiving neoadjuvant chemotherapy in CBCS (133 Black, 49 non-Black). Results: BIRC5 gene expression was significantly increased in tumors from 966 Black patients compared to 1,497 non-Black (p < 0.00001), adjusting for stage and subtype. BIRC5 high tumors were significantly more expressed in higher stage and basal-like breast cancer subtypes. BIRC5 high tumors were also significantly enriched for expression of genes involved in p53 loss and HRD. Furthermore, in an analysis of 182 CBCS patients, BIRC5 gene expression alone predicted pCR with similar overall AUC to ROR-PT multigene signatures (AUC 0.62 vs 0.64). Conclusions: Our study shows that survivin expression is particularly high in breast tumors from Black women. This was associated with more aggressive clinicopathological features in addition to p53 mutant and HRD status. Black women with breast cancer represent an area of unmet clinical need and could potentially benefit from anti-survivin targetable treatment strategies. Further studies are needed to help close this gap which constitutes the largest disparity among cancer-specific diseases.[Table: see text]

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Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

BMC Infectious Diseases ◽

10.1186/s12879-019-4529-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Chih-Huang Li ◽

Xiaolei Tang ◽

Samiksha Wasnik ◽

Xiaohua Wang ◽

Jintao Zhang ◽

...

Keyword(s):

Growth Hormone ◽

Vitamin D ◽

Growth Factor ◽

Kidney Failure ◽

Mechanistic Study ◽

Blood Levels ◽

Biological Functions ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D ◽

Fgf 23

Abstract Background Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. Methods We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. Results We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. Conclusions Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

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Differential Response to 1,25-dihydroxyvitamin D in Metastatic and Non-Metastatic Breast Cancer Cell Lines in Hypoxia (P05-006-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz030.p05-006-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Cited By ~ 1

Author(s):

Violet Kiesel ◽

Stephen Hursting ◽

Dorothy Teegarden

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Mammary Cancer ◽

Metastatic Breast ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Dihydroxyvitamin D ◽

1,25 Dihydroxyvitamin D

Abstract Objectives Prevention of metastasis is of utmost importance for increasing survival in breast cancer patients. Oxygen tension is variable throughout tumors, creating regions of hypoxia that have been linked with poor cancer prognosis. Hypoxia increases glycolytic flux via hypoxia-inducible factor-1α (HIF1α), and can therefore alter growth and survival of cancer cells. Our objectives are to (1) characterize changes in metabolism and survival that occur when metastatic and non-metastatic mammary cancer cell lines are cultured in hypoxia, and (2) determine whether 1,25-dihydroxyvitamin D (1,25(OH)2D) reduces overall survival in hypoxia. Methods We utilized Wnt oncogene-driven murine mammary cancer cells that are non-metastatic (M-Wnt) or that preferentially metastasize to the lung in vivo (metM-Wntlung). Viability of M-Wnt and metM-Wntlung cells treated with 10 nM 1,25(OH)2D and/or 20 mM 2-deoxyglucose (2DG, an inhibitor of glycolysis) was measured with MTT. Expression of HIF1α protein was determined by Western blotting. Results We show that 1,25(OH)2D treatment significantly decreased viability of metastatic metM-Wntlung cells grown in hypoxia by 41%, whereas viability of M-Wnt cells was not significantly impacted by 1,25(OH)2D treatment. Furthermore, treating cells with 2DG significantly decreased viability of both cells lines in hypoxia, with metM-Wntlung cells being more sensitive to 2DG. Interestingly, 1,25(OH)2D treatment partially rescued M-Wnt cells by 22% and metM-Wntlung cells by 24% when treated with 2DG in hypoxia. Finally, we show that M-Wnt cells have 1.9-fold increased expression of HIF1α protein compared to metM-Wntlung cells when grown in hypoxia. Conclusions Our results collectively suggest that non-metastatic M-Wnt cells are less sensitive to treatment with 1,25(OH)2D and 2DG in hypoxia than metastatic metM-Wntlungcells. These data may be explained, in part, by elevated expression of HIF1α in M-Wnt cells, which may contribute to their improved survival in hypoxia. Funding Sources National Institute of Health and USDA.

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A Comparison of Clinicopathological Features and Molecular Markers in British and Nigerian Women with Breast Cancer

Clinical medicine Oncology ◽

10.4137/cmo.s474 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S474

Author(s):

Isaac D. Gukas ◽

Anne C. Girling ◽

Barnabas M. Mandong ◽

Wendy Prime ◽

Barbara A. Jennings ◽

...

Keyword(s):

Breast Cancer ◽

Black Women ◽

White Women ◽

Clinical Stage ◽

Poor Response ◽

Tissue Banks ◽

Breast Cancer Patients ◽

Tumour Grade ◽

Nigerian Women ◽

Immunohistochemical Markers

Background Some studies have suggested that breast cancer in black women is more aggressive than in white women. This study's aim was to look for evidence of differences in tumour biology between the two cohorts. Methods This study compared the stage, grade and pathological expression of five immunohistochemical markers (oestrogen receptor [ER], progesterone receptor [PR], ERBB2, P53 and cyclin D1 [CCND1]) in tumour biopsies from age-matched cohorts of patients from Nigeria and England. Sixty-eight suitable samples from Nigerian (n = 34) and British (n = 34) breast cancer patients were retrieved from histology tissue banks. Results There were significant differences between the two cohorts in the expression of ER and CCND1; and stark differences in the clinical stage at presentation. But no significant differences were observed for tumour grade. Conclusion There was a significantly, low ER expression in the Nigerian cases which also predicts a poor response to hormonal therapy as well as a poorer prognosis. Differences in clinical stage at presentation will most likely influence prognosis between Nigerian and British women with breast cancer.

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Triple-Negative Breast Cancer: A Comparison of Race and Survival

The American Surgeon ◽

10.1177/000313481808400636 ◽

2018 ◽

Vol 84 (6) ◽

pp. 881-888

Author(s):

Matthew P. Doepker ◽

Scott D. Holt ◽

Martin W. Durkin ◽

Christopher H. Chu ◽

James M. Nottingham

Keyword(s):

Breast Cancer ◽

South Carolina ◽

Black Women ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

White Women ◽

Triple Negative ◽

Early Stage ◽

Breast Cancer Patients ◽

Aggressive Subtype

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a high prevalence in blacks. South Carolina demographically has a high percentage of blacks. This study examines survival and recurrence associated with TNBC in black and white women. A retrospective review of breast cancer patients within the Palmetto Health Cancer Registry was performed from 1999 to 2015. Patient demographics and tumor characteristics were collected and correlated with outcomes. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed. The total number of breast cancer patients in the registry was 1723 (1085—white and 638—black). The median follow-up was 48.4 months. The majority of cancers diagnosed in both cohorts were early stage (I, IIA, IIB, 93.4% vs 90.4% P = NS). We identified 332 patients with TNBC. Of those 332 patients, 144 (43.4%) were whites and 188 (56.6%) were blacks. Older age (P = 0.01), high-grade (P < 0.001), and black race (P < 0.001) were significantly associated with TNBC on multivariate analysis. Five- and 10-year OS was significantly worse in blacks with TNBC (P < 0.001). There was no difference in DSS or RFS between the two cohorts. TNBC disproportionately affects black women and is an aggressive subtype of breast cancer with limited treatment options compared with receptor-positive breast cancer. Black patients with TNBC in our study had statistically worse OS. These findings are similar to what has been reported in the literature and prompts further research in newer targeted therapies.

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