scholarly journals CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Siker Kimbung ◽  
Maria Inasu ◽  
Tor Stålhammar ◽  
Björn Nodin ◽  
Karin Elebro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Proportional Hazards ◽  
Tumor Biology ◽  
Cox Proportional Hazards ◽  
Receptor Expression ◽  
Cancer Specific Survival ◽  
Swedish Population ◽  
Estrogen Receptor Positive

Abstract Background 27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. Methods Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis. Results CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HRadjusted = 1.93, 95%CI = 1.26–2.97, P = 0.003; breast cancer-specific survival (BCSS), HRadjusted = 2.33, 95%CI = 1.28–4.23, P = 0.006] and among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 1.99, 95%CI = 1.24–3.21, P = 0.004; BCSS, HRadjusted = 2.78, 95%CI = 1.41–5.51, P = 0.003]. Among all patients in cohort 2 (median follow-up of 7.0 years), CYP27A1 expression was significantly associated with shorter OS and RFS in univariable analyses across the full follow-up period. However after adjusting for tumor characteristics and treatments, the association with survival after 5 years from diagnosis was non-significant among all patients [OS, HRadjusted = 1.08, 95%CI = 0.05–2.35, P = 0.83 and RFS, HRadjusted = 1.22, 95%CI = 0.68–2.18, P = 0.50] as well as among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 0.46 95% CI = 0.11–1.98, P = 0.30 and RFS, HRadjusted = 0.97 95% CI = 0.44–2.10, P = 0.93]. Conclusion CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.

scholarly journals Prognostic and predictive value of low estrogen receptor expression in breast cancer

2017 ◽  
Vol 24 (2) ◽  
pp. 106 ◽  
Author(s):  
A. Bouchard-Fortier ◽  
L. Provencher ◽  
C. Blanchette ◽  
C. Diorio
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hormonal Therapy ◽  
Proportional Hazards ◽  
Tumour Size ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Receptor Expression ◽  
Er Positive ◽  
Er Status

Purpose Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor (er)–positive breast cancer (bca); however, its effect on low-receptor cancers is unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in patients with weakly er-positive bca.Methods We identified 2221 bca patients who had been er-tested by ligand-based assay (lba) during 1976–1995 and who had been treated and followed until 2008. Cox proportional hazards models adjusted for age, body mass index, tumour size, nodal status, surgery, and chemotherapy were used to assess the effect of er level on bca survival in patients who received tamoxifen.Results Overall, 17% (383) of patients were within 0–3 fmol/mg cytosol protein, and 12% (266) were within 4–9 fmol/mg cytosol protein. Patients with er levels of 0–3, 4–9, 10–19, 20–49, and 50 fmol/mg or more cytosol protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60% respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal therapy. Within the latter group, er levels of 0–3, 4–9, 10–19, 20–49, and 50 fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001), 0.26 (p < 0.0001), and 0.31 (p < 0.0001)—the risk reduction being significant only for er levels of 10 fmol/mg or more cytosol protein.Conclusions Tamoxifen use in bca patients with a weakly positive er status (4–9 fmol/mg cytosol protein), compared with those having higher er levels (≥10 fmol/mg cytosol protein), is not associated with a significantly lower bca-specific mortality. Our results do not support treatment with anti-hormonal therapy for bca patients with a weakly positive er status as identified by lba.

scholarly journals Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satu Männistö ◽  
Kennet Harald ◽  
Tommi Härkänen ◽  
Mirkka Maukonen ◽  
Johan G. Eriksson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diet Quality ◽  
Proportional Hazards ◽  
Postmenopausal Breast Cancer ◽  
Healthy Eating Index ◽  
Cox Proportional Hazards ◽  
Healthy Diet ◽  
Food Culture ◽  
Alternative Healthy Eating Index

AbstractThere is limited evidence for any dietary factor, except alcohol, in breast cancer (BC) risk. Therefore, studies on a whole diet, using diet quality indices, can broaden our insight. We examined associations of the Nordic Diet (mNDI), Mediterranean diet (mMEDI) and Alternative Healthy Eating Index (mAHEI) with postmenopausal BC risk. Five Finnish cohorts were combined including 6374 postmenopausal women with dietary information. In all, 8–9 dietary components were aggregated in each index, higher total score indicating higher adherence to a healthy diet. Cox proportional hazards regression was used to estimate the combined hazard ratio (HR) and 95% confidence interval (CI) for BC risk. During an average 10-year follow-up period, 274 incident postmenopausal BC cases were diagnosed. In multivariable models, the HR for highest vs. lowest quintile of index was 0.67 (95 %CI 0.48–1.01) for mNDI, 0.88 (0.59–1.30) for mMEDI and 0.89 (0.60–1.32) for mAHEI. In this combined dataset, a borderline preventive finding of high adherence to mNDI on postmenopausal BC risk was found. Of the indices, mNDI was more based on the local food culture than the others. Although a healthy diet has beneficially been related to several chronic diseases, the link with the etiology of postmenopausal BC does not seem to be that obvious.

Impact of race and socioeconomic status on breast cancer outcomes within the AJCC staging system.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18565-e18565
Author(s):  
Olga Kantor ◽  
Monica L. Wang ◽  
Kimberly Bertrand ◽  
Mariana Chavez-MacGregor ◽  
Rachel A. Freedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Socioeconomic Status ◽  
Proportional Hazards ◽  
Census Data ◽  
Tumor Biology ◽  
Staging System ◽  
Cox Proportional Hazards ◽  
Cancer Outcomes ◽  
Black Race ◽  
Breast Cancer Outcomes

e18565 Background: The persistent racial and socioeconomic status (SES) disparities in breast cancer outcomes are partially attributed to propensity towards more aggressive cancers or presentation at higher stages among these groups. Chronic stressors related to race and SES are another major mechanism underlying these inequities. This study aims to examine the effect of race and SES within the AJCC 8th-edition staging system, which incorporates anatomic extent of disease and tumor biology. Methods: The SEER breast cancer database linked with county-level census data was used to identify patients with invasive breast cancer from 2010-2015. The database includes a composite SES-index which was analyzed in quintiles. Cox proportional-hazards regression was used to estimate disease-specific survival (DSS). Results: 259,852 patients were included: 176,369 (67.9%) non-Hispanic white, 28,510 (11.0%) Black, 29,737 (11.4%) Hispanic, and 22,887 (8.8%) Asian. Black race, lower SES, public insurance, lower education, and increased poverty were associated with decreased DSS. Adjusted survival analysis for patient, SES, tumor, and treatment characteristics demonstrated that patients of black race had inferior DSS within each stage. Fully adjusted models also showed patients residing in lower SES counties had inferior DSS [Table]. Conclusions: Racial and SES disparities in breast cancer-specific mortality were evident across all stages of disease. Future efforts to improve breast cancer outcomes should systematically assess and address racial and socioeconomic factors as fundamental drivers of inequitable outcomes. Adjusted 5-year DSS Estimates, Stratified by Race and SES.[Table: see text]

scholarly journals Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 684 ◽  
Author(s):  
Nadiia Lypova ◽  
Lilibeth Lanceta ◽  
Alana Gipson ◽  
Stephanie Vega ◽  
Rodolfo Garza-Morales ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Viral Entry ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Type I ◽  
Development Of Resistance ◽  
Estrogen Receptor Positive ◽  
Entry Receptor ◽  
Resistant Cells

While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolytic adenovirus (OAd) known as Ad5/3-delta24. Analysis of ER+ and ER− palbociclib-resistant cells revealed two clearly distinguishable responses to the OAd. While ER+ palbociclib-resistant cells displayed a hypersensitive phenotype to the effects of the OAd, ER− palbociclib-resistant cells showed a resistant phenotype to the OAd. Hypersensitivity to the OAd in ER+ palbociclib-resistant cells correlated with a decrease in type I interferon (IFN) signaling, an increase in viral entry receptor expression, and an increase in cyclin E expression. OAd resistance in ER− palbociclib-resistant cells correlated with an increase in type I IFN signaling and a marked decrease in viral entry receptor. Using the OAd as monotherapy caused significant cytotoxicity to both ER+ and ER− palbociclib-sensitive cell lines. However, the addition of palbociclib increased the oncolytic activity of the OAd only in ER+ palbociclib-sensitive cells. Our studies provide a mechanistic base for a novel anti-cancer regimen composed of an OAd in combination with palbociclib for the treatment of ER+ breast cancer.

scholarly journals Factors associated with prolonged overall survival in patients with postmenopausal estrogen receptor-positive advanced breast cancer using real-world data: a follow-up analysis of the JBCRG-C06 Safari study

Breast Cancer ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 389-398
Author(s):  
Hidetoshi Kawaguchi ◽  
Norikazu Masuda ◽  
Takahiro Nakayama ◽  
Kenjiro Aogi ◽  
Keisei Anan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Palliative Chemotherapy ◽  
Nuclear Grade ◽  
Younger Age ◽  
Estrogen Receptor Positive ◽  
Survival Risk

Abstract Background Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients. Methods OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study. Results A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age (< 60 years), longer time from ABC diagnosis to fulvestrant use (≥ 3 years), no prior palliative chemotherapy before fulvestrant use, and progesterone receptor (PgR) negativity (PgR−) were significantly correlated with prolonged OS (median 7.0 years). For cases with histological or nuclear grade data, lower histological or nuclear grades were also correlated with longer OS. In recurrent metastatic cases, long disease-free interval (DFI) was not correlated with longer OS. Conclusions In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR−, and lower histological or nuclear grade correlated positively with prolonged OS.

Does race affect outcomes in triple negative breast cancer (TNBC)?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17543-e17543
Author(s):  
S. Ahmed ◽  
M. M. Mirza ◽  
A. Farooq ◽  
L. Kronish ◽  
M. Jahanzeb ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Racial Differences ◽  
Statistical Significance ◽  
Menopausal Status ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Stage At Diagnosis ◽  
Cancer Specific Survival ◽  
The Impact

e17543 Background: TNBC is associated with a worse prognosis than luminal subtypes. There is discordance among studies assessing the impact of race on outcomes of TNBC. Our objective was to assess whether African American (AA) vs. Caucasian (CA) race predicted survival outcomes for women with TNBC treated at a single institution in Memphis, TN. Secondary objectives were to examine the association of race with patient and tumor characteristics. Methods: Patients with stage I-III TNBC were identified from our breast cancer database and confirmed by review of pathology reports. Event free survival (EFS) was measured from the date of surgery to the date of first recurrence (locoregional, distant, or contralateral), death from breast cancer or last follow-up. Breast cancer specific survival (BCSS) was measured from the date of surgery to the date of death from breast cancer or last follow-up. Fisher's exact test was used for association between variables, Kaplan Meier method for survival estimates, and log rank test for survival comparison between groups (p < 0.05: significant). Cox proportional hazards models with patient, tumor and treatment variables were fitted for EFS and BCSS. Results: Of the 105 patients with TNBC, 71% were AA. There was no significant association between race and stage at diagnosis (p = 0.68). 71% of AA women were < 55 years old and 43% were pre-menopausal vs. 50% and 23% of CA women respectively. There was a trend towards association of race with age and menopausal status (p = 0.08). Ninety three percent of the patients received neo/adjuvant chemotherapy. With a median follow up of 26 months, 26% of AA vs. 20% of CA women had an event (p = 0.62). Overall 3 year EFS and BCSS estimates were 69% and 82% respectively. Racial differences in EFS and BCSS for AA vs. CA (65% vs. 80% and 78% vs. 89%, respectively) did not achieve statistical significance (log rank p = 0.22 for EFS and 0.26 for BCSS). Race was not a significant predictor of EFS or BCSS on uni-variable or multi-variable analysis. Stage at diagnosis retained significance for EFS and BCSS on uni-variable and multi-variable testing. Conclusions: Race did not affect outcomes in our cohort of TNBC patients treated similarly. The high event rate underscores the poor prognosis of TNBC and the need for more effective therapies. No significant financial relationships to disclose.

Race as an independent factor for survival in breast cancer patients according to analysis of the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18155-e18155 ◽  
Author(s):  
Drew Carl Drennan Murray ◽  
Shruti Bhandari ◽  
Phuong Ngo ◽  
Sarah Mudra ◽  
Rachana Shirish Lele ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Early Stage ◽  
Tumor Biology ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Independent Factor ◽  
Breast Cancer Patients ◽  
Delayed Treatment

e18155 Background: Black (B) women after early stage of diagnosis have been shown to have double the risk of white (W) women for failing to receive adjuvant chemotherapy. Despite lower incidence of breast cancer in B patients, they are more likely to die of the disease. Worse outcomes in B populations have been related to clinical and socioeconomic factors. However, the determination of improved access and its effects on survival in black patients remains uncertain. Methods: 1042844 patients diagnosed between 2004 and 2014 with stage I-III breast cancer were identified in the NCDB. Only W and B races were analyzed with established risk factors of age, stage, comorbidity score, and insurance status. Data was analyzed using univariable and multivariable logistic and Cox proportional hazards regression models. Odds Ratio (OR) for binary outcome, Hazard Ratio (HR) for time-to-event (survival) outcome along with 95% confidence interval (95% CI) are reported. Results: Among the total population 85.5% were W, 10.6% B, and 3.9% other. B were more likely to be uninsured (OR: 1.66; 95% CI: 1.59 - 1.72; p < 0.0001), or have Medicaid (OR: 2.01; 95% CI: 1.96 - 2.07; p < 0.0001). B were also diagnosed at later stage (stage 3 OR: 1.59; 95% CI: 1.57 - 1.63; p < 0.0001) with higher co-morbidities (OR: 2.49; 95% CI: 2.34 - 2.67; p < 0.0001) consistent with prior studies. B were more likely to experience delayed treatment (OR: 2.15; 95% CI: 2.10 - 2.20; p < 0.0001). B race remained an independent factor associated with higher likelihood of death compared to W patients (HR: 1.32; 95% CI: 1.3 - 1.34; p < 0.0001) in multivariable analysis. Conclusions: This large database study demonstrates that even when controlling for established risk factors such lack of insurance or Medicaid, higher comorbidities, and later stage at diagnosis, B patients were more likely to experience delays in treatment initiation and worse overall survival. This suggests race remains an independent risk factor for poor outcome even when clinical factors are matched. Further analysis including tumor biology should be examined to better understand this persistent disparity.

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