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.

Predictors of Tamoxifen Discontinuation Among Older Women With Estrogen Receptor–Positive Breast Cancer

2008 ◽  
Vol 26 (4) ◽  
pp. 549-555 ◽  
Author(s):  
Cynthia Owusu ◽  
Diana S.M. Buist ◽  
Terry S. Field ◽  
Timothy L. Lash ◽  
Soe Soe Thwin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Older Women ◽  
Proportional Hazards ◽  
Care Delivery ◽  
Breast Conserving Surgery ◽  
Cox Proportional Hazards ◽  
Adjuvant Tamoxifen ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) –positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Patients and Methods Within six health care delivery systems, we identified women ≥ 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Results Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged ≥ 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Conclusion Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

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.

Breast cancers with stem cell-like features delineate endocrine responsiveness

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10517-10517
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
R. Gaetje ◽  
R. Diallo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Lymph Node ◽  
Survival Rates ◽  
Disease Recurrence ◽  
Normal Breast ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Er Positive ◽  
Er Status

10517 Background: Endocrine responsiveness is one of the most important characteristics of breast cancer. The negative association between expression of the estrogen receptor (ER) and proliferation detected in normal breast is frequently lost in breast cancers leading to receptor independent growth and poor patients’ prognosis. Methods: Microarray analysis of 171 breast cancer samples allowed the discrimination of a KIT+ tumor group by using a set of genes coregulated with the “stem cell factor” receptor KIT. Validation was performed on three independent datasets encompassing 637 samples. Furthermore the response to endocrine treatment only was analyzed in a dataset of 700 patients. Results: KIT+ tumors are transcriptionally related to proposed mammary stem cells. Two types of KIT+ tumors were identified which are characterized by their positive and negative ER status, respectively. The inverse link of ER expression and proliferation is perfectly conserved within the KIT+ tumor groups, while it is uncoupled among half of the KIT-Low ER positive tumors. Those “uncoupled” ER positive tumors with altered ER response are characterized by a prognosis inferior to the ER negative cancers despite an apparent positive ER status (hazard ratio for disease recurrence, 2.07; 95% CI 1.53–2.81; P<0.001). Moreover, the 5 and 10 year survival rates of lymph node negative “uncoupled” tumors are even worse than those of lymph node positive “normal” ER positive cancers. While all ER positive patients seem to profit from endocrine treatment the relative benefit was reduced in uncoupled tumors (21.2 % vs. 31.7 %). Conclusions: The classification of breast cancers according to this biologically based model identified clinical relevant tumor groups whose further characterization will have important implications. Moreover, since the ability to recognize malfunctions in ER pathways largely depends on an appropriate reference system, the KIT+ tumors could allow a dissection of estrogen responsiveness giving crucial insights for prediction of response to endocrine therapy. No significant financial relationships to disclose.

Role of clinical and histologic factors in decision making on adjuvant therapy of small HER2-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11053-e11053
Author(s):  
Faisal Azam ◽  
Saif Yousif ◽  
Aarifah Aaseem ◽  
Eliyaz Ahmed
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Tumour Size ◽  
Screening Mammography ◽  
Her2 Positive ◽  
Node Negative ◽  
Er Positive ◽  
Her 2 ◽  
Er Status

e11053 Background: With increased use of screening mammography for breast cancer (BC), the incidence of small (T1a, b), node negative BC has increased. These cancers are considered low-risk and hence not offered adjuvant (adj) chemotherapy (CT). However, increasing retrospective studies suggest that outcomes in small node negative HER-2 positive BC might be worse than the HER-2 negative tumours of similar size. Current guidelines generally do not recommend adj CT and Trastuzumab (T) for small (T1 a, b) HER-2 positive tumours. As a part of our ongoing audit on the outcome of small HER -2 positive BC, we wished to determine the factors that oncologists consider in decision making on adj treatment of these tumours in the absence of clear guidelines. Methods: Patients (pts) with a diagnosis of node negative T1a, b, HER-2 positive BC treated across our cancer network, between Jan 2008 and Dec 2011, were identified from our electronic database. Results: A total 230 pts had stage T1, HER 2 +ve BC. Out of those 41(17%) pts had tumour size of < 1cm (13, 31%pts were T1a and 28, 74%pts wereT1b) and node negative disease. Median age was 55 years (29-84yrs). 33 Pts had BCS and 8 pts had mastectomy. All pts with BCS received adj radiotherapy and all pts who were ER positive received adj endocrine therapy. 21(51%) out of 41pts received adjuvant CT and T. All pts had anthracycline based CT. The clinical and pathological characteristics of pts who received adj CT and T were as follows; Median age- 50 (33-64years), grade 1- 1(4%), grade 2 – 9(43%), grade 3- 11(53%), LVI present- 2(9%), LVI absent- 7(34%), LVI unknown – 12(57%), ER positive- 16(76%), ER negative – 5(24%). None of the pts had recurred or died at the time of analysis of the data and longer follow up is needed for survival analysis. Conclusions: In the absence of clear guidelines on adj CT and T in node negative small HER-2 positive BC, the oncologists relied on the traditional factors such as grade, ER status in risk stratification and decision on adj therapy. Tumour grade was the most important factor but age and ER status were not discriminating factors in this study. Prospective randomised trials needed to clearly define the role of adj systemic therapy in this group of pts.

scholarly journals Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

2013 ◽  
Vol 31 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Hatem A. Azim ◽  
Niels Kroman ◽  
Marianne Paesmans ◽  
Shari Gelber ◽  
Nicole Rotmensz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Pregnancy Outcome ◽  
Estrogen Receptor Status ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Er Positive ◽  
The Impact ◽  
Disease Free ◽  
Er Status

Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

Estrogen receptor expression and efficacy of docetaxel in early breast cancer: A pooled analysis of 3,490 patients included in two randomized trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 537-537 ◽  
Author(s):  
F. Andre ◽  
K. Broglio ◽  
H. Roche ◽  
M. Martin ◽  
F. Penault-Lorca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Randomized Trials ◽  
Pooled Analysis ◽  
Relative Effect ◽  
Risk Of Death ◽  
Er Positive ◽  
Er Expression ◽  
Er Status

537 Background: It has been suggested that estrogen receptor (ER) expression is associated with relative resistance to adjuvant chemotherapy. The efficacy of adjuvant chemotherapy is still matter of controversy in this subset of patients. The aim of the present study was to assess the efficacy of docetaxel according to ER expression in adjuvant treatment trials. Patients and Methods: The efficacy of docetaxel according to ER expression was assessed in a pooled analysis of two randomized studies (BCIRG001 and PACS01) that included overall 3,490 patients with axillary node positive breast cancer. These studies compared either 3 (PACS01) or 6 (BCIRG001) cycles of a docetaxel-containing regimen, to a chemotherapy that did not contain docetaxel. Hazard ratios (HR) for death were determined by a Cox model adjusted for clinical characteristics (age, T size and number of lymph node involved). Interaction between docetaxel efficacy and ER expression was tested. Results: ER status was assessable in 3,329 patients (95%). The median age was 49 years old (range, 23–70). ER was expressed in 2,493 tumors (74%). In patients with assessable ER status (n=3329), docetaxel was associated with a significant reduction in the risk of death (HR=0.69; 95%CI: 0.51–0.92, p=0.01). Docetaxel therapy was associated with a 30% reduction in the risk of death in ER-positive disease (HR=0.70; 95%CI: 0.54–0.91) and a 31% reduction in the risk of death in ER-negative disease (HR=0.69; 95% CI: 0.52–0.94). Test for interaction did not detect any statistically significant difference in the relative effect of docetaxel according to ER status (HR for interaction=1.03; p=0.87). Conclusion: In this pooled analysis of two randomized trials, the relative effect of docetaxel on overall survival in adjuvant setting was not different between ER-positive and ER-negative disease. Docetaxel was associated with a significant risk reduction of death in patients with ER-positive disease. No significant financial relationships to disclose.

Prognostic and predictive value of a low estrogen receptor expression in breast cancer: A retrospective study from a reference center.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 627-627
Author(s):  
Caroline Diorio ◽  
Antoine Bouchard-Fortier ◽  
Caty Blanchette ◽  
Louise Provencher
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Hormonal Therapy ◽  
Cancer Mortality ◽  
Proportional Hazards Model ◽  
Breast Cancer Mortality ◽  
Cox Proportional Hazards Model ◽  
Receptor Expression ◽  
P Value

627 Background: Threshold of estrogen receptors positivity in breast cancer has been lowered to ≥1% of stained cells by immunohistochemistry testing. This change was based on experts’ recommendations from the 2009 St Gallen International Expert Consensus and from the 2010 guidelines of the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP). However few studies support these guidelines and the benefit of treating weakly positive estrogen receptor tumors (1-9%) is unknown. Methods: We identified 2221 breast cancer patients with estrogen receptors tested by ligand-based assay, treated and followed in our institution between 1976 and 2008. Date and cause of death were identified through linkage to Quebec Mortality File. A multivariate Cox proportional-hazards model was used to assess the effect of estrogen receptor levels on breast cancer mortality in patients who received hormonal therapy (tamoxifen). Results: In patients with low estrogen receptors, 17% (383 patients) were within 0-3 fmol/mg of cytosol and 12% (266 patients) were within 4-9 fmol/mg of cytosol. Patients with estrogen receptor levels of 0-3, 4-9, 10-19, 20-49, and ≥50 fmol/mg of cytosol had a 20-year breast cancer survival rate of 56%, 56%, 63%, 71% and 60% respectively. From the 2221 patients, 661 (29.8%) received hormonal therapy. In these patients, estrogen receptor levels of 0-3, 4-9, 10-19, 20-49 and ≥50 fmol/mg of cytosol were associated with lower breast cancer mortality (HR (p-value) of 1.00 (reference), 0.59 (0.09), 0.19 (<0.0001), 0.26 (<0.0001) and 0.31 (<0.0001) respectively); with significant mortality reduction only for estrogen receptor levels ≥10 fmol/mg of cytosol. Conclusions: A weak expression of estrogen receptors (<10 fmol/mg) in breast cancer is associated with increase breast cancer mortality. Our results did not show a significant benefit to treat these patients with hormonal therapy as oppose to those with estrogen receptor levels ≥10 fmol/mg of cytosol. To further support these findings, a similar study should be repeated in patients with estrogen receptors tested by immunohistochemistry.

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