Effect of the third generation selective estrogen receptor modulator arzoxifene on mammographic breast density

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 562-562
Author(s):  
B. F. Kimler ◽  
G. Ursin ◽  
C. J. Fabian ◽  
J. R. Anderson ◽  
C. Chamberlain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
High Risk ◽  
Phase Ii ◽  
Breast Density ◽  
Receptor Expression ◽  
Mammographic Breast Density ◽  
Computer Assisted ◽  
Breast Cancer Patients ◽  
Dense Area

562 Background: Arzoxifene (ARZ) is currently being studied for treatment of breast cancer patients in a Phase II trial because of tamoxifen-like efficacy but lack of uterine agonist effect. We conducted a Phase II chemoprevention trial in women at high risk for development of breast cancer on the basis of personal or family history. Methods: Potential subjects had multiple biomarkers assessed, including random periareolar fine needle aspiration (RPFNA) with breast epithelial cells processed for cytomorphology and immunocytochemistry. Women who exhibited cytologic hyperplasia ± atypia were eligible for enrollment. Subjects were stratified on the basis of atypia, estrogen receptor expression, menopause status, germline BrCa1/2 mutation status, and accrual site. Subjects were randomized (double-blind) between placebo and ARZ (LY353381.HCI, 20 mg daily) for 6 mo, with an option to continue on study for another 6 mo while receiving open-label ARZ. Assessments conducted at baseline, 6 mo, and 12 mo included mammographic breast density. Mammograms were digitized to image files which were cropped to remove labels and dates, and then identified by a study subject ID number and a random coding for baseline, 6 or 12 mo. This allowed the reader (GU) to view the three files for a subject, but to remain blinded as to the sequence of the films or the study agent. The files were assessed for mammographic density using the Madena computer-assisted system. Results: Of 199 subjects enrolled on the study, 52% were pre-menopausal; with 101 women randomized to placebo and 98 to ARZ. At baseline, mean values were comparable for placebo and ARZ groups for breast area (∼244 cm2), total dense area (∼100 cm2), and the percent of the breast at increased density (41.3% vs 46.2%). After 6 mo, there were minimal changes in total breast area (P=0.13); but statistically significant decreases (P<0.001) for the comparison of placebo vs ARZ (2-sided T-test) for change in both dense area (+3.8 vs −12.9 cm2) and percent breast density (+0.8% vs −4.6%). Conclusions: The 3rd generation SERM arzoxifene administered for 6 mo produces statistically significant decreases in mammographic breast density relative to placebo in women at high risk for development of breast cancer. No significant financial relationships to disclose.

scholarly journals Benign breast disease and changes in mammographic breast density

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Laura L. Reimers ◽  
Mandy Goldberg ◽  
Parisa Tehranifar ◽  
Karin B. Michels ◽  
Barbara A. Cohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Benign Breast Disease ◽  
Breast Disease ◽  
Mammographic Breast Density ◽  
Computer Assisted ◽  
First Birth ◽  
Dense Area ◽  
Nulliparous Women ◽  
Using Data

Abstract Background Mammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer. Methods Using data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959–1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method. Results A prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1–27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7–8% higher percent MBD (β = 7.25, SE = 2.43, p-value< 0.01 and β = 7.84, SE = 2.98, p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (β = −0.22, SE = 2.40, p-value = 0.93). Conclusion Women with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.

scholarly journals Tumour Size at Detection According to Different Measures of Mammographic Breast Density

2009 ◽  
Vol 16 (3) ◽  
pp. 140-146 ◽  
Author(s):  
Carolyn Nickson ◽  
Anne M Kavanagh
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Tumour Size ◽  
Mammographic Screening ◽  
Cancer Prognosis ◽  
Mammographic Breast Density ◽  
Interval Cancers ◽  
Dense Area ◽  
Screening Strategies ◽  
Continuous Measures

Objectives Breast cancer prognosis is better for smaller tumours. Women with high breast density are at higher risk of breast cancer and have larger screen-detected and interval cancers in mammographic screening programmes. We assess which continuous measures of breast density are the strongest predictors of breast tumour size at detection and therefore the best measures to identify women who might benefit from more intensive mammographic screening or alternative screening strategies. Setting and methods We compared the association between breast density and tumour size for 1007 screen-detected and 341 interval cancers diagnosed in an Australian mammographic screening programme between 1994 and 1996, for three semi-automated continuous measures of breast density: per cent density, dense area and dense area adjusted for non-dense area. Results After adjustment for age, hormone therapy use, family history of breast cancer and mode of detection (screen-detected or interval cancers), all measures of breast density shared a similar positive and significant association with tumour size. For example, tumours increased in size with dense area from an estimated mean 2.2 mm larger in the second quintile (β = 2.2; 95% Cl 0.4–3.9, P < 0.001) to mean 6.6 mm larger in the highest decile of dense area (β = 6.6; 95% Cl 4.4–8.9, P < 0.001), when compared with first quintile of breast density. Conclusions Of the breast density measures assessed, either dense area or per cent density are suitable measures for identifying women who might benefit from more intensive mammographic screening or alternative screening strategies.

scholarly journals Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Young-Joon Kang ◽  
Han-Byoel Lee ◽  
Yun Gyoung Kim ◽  
JaiHong Han ◽  
Yumi Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Progesterone Receptor ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Receptor Expression ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
End Point

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

Correlation of mammographic breast density with Ki-67 expression in benign breast epithelial cells obtained by random periareolar fine needle aspiration of high risk women

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1011-1011
Author(s):  
Q. J. Khan ◽  
B. F. Kimler ◽  
E. J. Smith ◽  
A. P. O’Dea ◽  
P. Sharma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Mammographic Density ◽  
Breast Density ◽  
Fine Needle Aspiration ◽  
Needle Aspiration ◽  
Mammographic Breast Density ◽  
Ki 67 ◽  
Fine Needle ◽  
Cytologic Atypia

1011 
 >Background: Known risk factors for breast cancer development include elements incorporated into the Gail risk model, mammographic breast density and cytologic atypia detected by Random Periareolar Fine Needle Aspiration (RPFNA). Ki-67 expression is a possible risk biomarker and is currently being used as a response biomarker in chemoprevention trials. We have previously shown that Ki-67 expression is higher in RPFNA specimens of benign breast cells exhibiting cytologic atypia. It is not known whether there is a correlation between mammographic density and Ki-67 expression in benign breast ductal cells obtained by RPFNA. Methods: 344 women at high risk of developing breast cancer (based on personal or family history) seen at The University of Kansas Medical Center high risk breast clinic, who underwent RPFNA with cytomorphology and Ki-67 assessment, plus a mammogram were included in the study. Mammographic breast density was assessed using the Cumulus program. Categorical variables were analyzed by Chi-square test and continuous variables were analyzed by non-parametric test and linear regression. Results: 40% of women were premenopausal, 7% perimenopausal and 53% were postmenopausal. Median age was 49 years, median 5 year Gail Risk was 2.2%, and median Ki-67 was 1.9%. Median mammographic breast density was 37%. Ki-67 expression increased with cytologic abnormality and number of cells collected, but was unrelated to Gail risk (as observed previously). Breast density was higher in pre-menopausal women (p=0.001), those with lower BMI (p< 0.001), and lower 5-year Gail risk (p=0.012); Breast density showed no correlation with Ki-67 expression or cytomorphology. Conclusion: Given the lack of correlation of mammographic breast density with either cytomorphology or Ki-67 expression in RPFNA specimens, mammographic density and Ki-67 expression should be considered as potentially complementary response biomarkers for breast cancer chemoprevention trials. No significant financial relationships to disclose.

COX-2 expression and clinical outcome in early-stage breast cancer patients treated with adjuvant chemotherapy: A prospective study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22165-e22165
Author(s):  
A. Kargi ◽  
M. Ozdogan ◽  
H. Bozcuk ◽  
E. Pestereli ◽  
M. Artac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Menopausal Status ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Breast Cancer Patients ◽  
Cox 2 ◽  
A Prospective Study

e22165 Background: To evaluate the association of cox-2 expression with the outcome after adjuvant chemotherapy in patients with early breast cancer. Methods: This was planned as a prospective study recruiting consecutive patients receiving adjuvant anthracycline based chemotherapy and with available tissue blocks permitting all immunohistochemical analyses. Cox-2 expression, in addition to other classical biological factors, was evaluated with immunohistochemistry. Disease and patient related, and biological predictors of both overall survival (OAS) and relapse free survival (RFS) were analyzed by Cox regression analysis. Median and mean survival times were calculated according to the Kaplan Meier method. Results: A total of 88 patients were recruited over a period of 24 months. Median age was 45 (29 to 70), and 60% of subjects were premenapausal. Median tumour diameter and number of axillary lymph nodes involved were 2 cm (1 to 6 cm), and 2 (0 to 15), respectively. Median follow up is 74.2 months. Univariate analysis revealed menopausal status and estrogen receptor expression as predictors of OAS, and menopausal status as the correlate of RFS. Multivariate analysis confirmed the independent predictive value of both menopausal status and estrogen receptor expression for OAS (P=0.009, HR=4.18, and P=0.014, HR=0.20, respectively). No multivariate analysis could be performed for RFS. Cox-2 expression was not associated with OAS or RFS (P=0.208, HR=1.92, and P=0.132, HR=1.89, respectively). Interestingly, Cox-2 expression was correlated with Estrogen receptor (ER) and Progesteron receptor (PR) expression (P=0.006, R=-0.303, and P=0.004, R=-0.312, respectively). Conclusions: Cox-2 expression fails to predict clinical outcome of early breast cancer patients treated with adjuvant chemotherapy. However, Cox-2 expression seems to negatively correlate with ER and PR expression. It should be tested in this patient population whether Cox-2 may play a part in hormonal resistance. No significant financial relationships to disclose.

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