Effect of celecoxib, a specific cyclooxygenase 2 inhibitor, on the apoptotic and mitotic indexes of breast cancer in patients with early stage disease

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14132-14132
Author(s):  
A. H. Tfayli ◽  
M. Cherry ◽  
J. Yang ◽  
K. Kojouri ◽  
M. Jafari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Metastatic Breast ◽  
Surgical Excision ◽  
Small Sample ◽  
Matched Pair ◽  
Ki 67 ◽  
Early Stage Disease ◽  
Days Of Therapy ◽  
Cox 2

14132 Background: To assess whether the administration of celecoxib, a specific cyclooxegenease-2 (COX-2) inhibitor, to patients with breast cancer alters the proliferative and apoptotic indexes of their tumors. Methods: Women newly diagnosed with non metastatic breast cancer were enrolled into the study after undergoing a diagnostic core needle biopsy. Patients received celecoxib treatment at 400 mg orally twice a day for 14 days, and then underwent surgical excision of their tumor. Core biopsies obtained at the time of initial diagnostic procedure and surgical excision specimens were stained for Ki-67, as well as COX-2 and cleaved poly (ADP-ribose) polymerase (PARP) expression (as an apoptosis marker). Appropriate negative and positive controls were included. We assessed the difference in Ki- 67, COX-2 and cleaved PARP expression levels, before and after treatment using the Wilcoxon’s matched-pair ranks test and the McNemar’s test. Results: 16 patients were enrolled. The median age was 54.6 years. ER and/or PR expression was present in 81% of tumors; Her-2 neu overexpression was present in 25%. No significant change in COX-2 or cleaved PARP expression was noticed in the post intervention specimen compared to the core biopsies. Surprisingly, there was a significant increase in the Ki-67 expression (p < 0.009). Conclusions: we have conducted a short term prospective study to assess the effects of celecoxib, on the proliferative and apoptotic indexes in patients with early stage breast cancer. We have found an increase in the Ki-67 activity, with no significant down regulation of COX-2 or increase in cleaved PARP expression with 14 days of therapy. This could be partly due to the small sample size. [Table: see text]

Use of comprehensive next-generation sequencing to identify pathogenic germline variants with therapeutic relevance in metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
Nicole Margo Grogan ◽  
Yi-Mi Wu ◽  
Dan R. Robinson ◽  
James M. Rae ◽  
Norah Lynn Henry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Testing ◽  
Early Stage ◽  
Metastatic Breast ◽  
Exome Capture ◽  
Sample Collection ◽  
Direct Role ◽  
Early Stage Disease ◽  
Therapeutic Relevance

10527 Background: Among patients with early-stage breast cancer, approximately 6-10% have a pathogenic germline variant (PGV) conferring inherited cancer predisposition. In contrast, few studies have explored the frequency and types of PGVs identified in patients with metastatic breast cancer (MBC); therefore, additional data is needed. Methods: From 2011-2020, 278 patients with MBC underwent fresh tumor biopsy and blood sample collection for paired tumor/normal DNA (targeted exome capture with analysis of 1700 genes) and RNA (tumor transcriptome) sequencing through the Michigan Oncology Sequencing (Mi-ONCOSEQ) program. Somatic and germline alterations were annotated and classified according to degree of clinical actionability with results returned to treating oncologists. Retrospective chart review was performed to determine if: 1) a PGV was identified prior to Mi-ONCOSEQ testing, 2) patients met National Comprehensive Cancer Network (NCCN) guideline criteria for genetic testing on the basis of personal or family cancer history and 3) patients received subsequent therapy informed by a PGV. Results: Forty-eight of the 278 patients (17.3%) had at least one PGV identified, with a total of 50 PGVs identified in this cohort. Only twelve of these PGVs (24%) had been identified prior to Mi-ONCOSEQ testing. The most frequent PGVs identified were in CHEK 2 (n = 9, 18%), MUTYH (n = 6, 12%), BRCA 1 (n = 5, 10%), BRCA2 (n = 5, 10%), ATM (n = 4, 8%) and PALB2 (n = 4, 8%). Somatic loss of heterozygosity events (LOH) occurred in 30 of the 50 cases with PGVs identified (60%). LOH events were observed in 83.3% of BRCA1, BRCA2, ATM and PALB2 PGVs, but were less frequently observed with CHEK2 (33.3%) and MUTYH (66.7%). Two hundred sixteen out of 278 patients (77.7%) in this cohort met NCCN criteria for genetic testing, although six patients with a PGV identified (CHEK2: n = 5; MUTYH: n = 1) did not meet NCCN criteria. Twenty-nine PGVs identified (58%) had potential therapeutic relevance and 11 patients (22.9%) received targeted therapy based on the PGV. Conclusions: The frequency of PGVs identified in this cohort is nearly double the frequency reported for patients with early-stage disease, suggesting that certain PGVs may confer worse prognosis. CHEK2, the most frequently identified PGV, was less likely to have an identifiable LOH event. The direct role of CHEK2 PGVs in tumor pathogenesis is uncertain, but other mechanisms of silencing the wild type allele must be considered. Despite the majority of patients meeting NCCN criteria for genetic testing, those with PGVs in CHEK2 were less reliably identified by this mechanism. The majority of PGVs identified were of potential therapeutic relevance, supporting the recommendation for genetic testing in all patients with MBC.

scholarly journals Among the Metavivors: Social Media and Illness Narratives of Stage IV Breast Cancer Patients

2018 ◽  
Vol 4 (1) ◽  
pp. 1-24
Author(s):  
Susan Jacobson
Keyword(s):  
Breast Cancer ◽  
Social Media ◽  
Metastatic Breast Cancer ◽  
Civil Rights ◽  
Early Stage ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Early Stage Disease ◽  
Stage Iv Breast Cancer

Dominant breast cancer narratives equate early detection and screening with “cure,” advocate for “awareness,” and identify women who undergo treatment for early stage disease as “survivors.” Left out of these narratives are the “metavivors”: women and men diagnosed with “incurable” metastatic breast cancer, also known as Stage IV. This article uses case studies to profile four women living with metastatic breast cancer who turn to social media to tell their stories: Sally, a former civil rights attorney turned breast cancer activist, who uses social media platforms to organize and mobilize Stage IV patients to advocate on their own behalf; Jane, who plows through databases of dense medical research to find treatments to save her own life; Jenny, a young mother dying of metastatic breast cancer who shares her experiences on a YouTube channel; and Grace, who participates in an early-stage clinical trial that she believes “cured” her, a term eschewed by both the medical establishment and fellow metavivors.

scholarly journals Among the Metavivors: Social Media and Illness Narratives of Stage IV Breast Cancer Patients

2018 ◽  
Vol 4 (1) ◽  
pp. 1-24
Author(s):  
Susan Jacobson
Keyword(s):  
Breast Cancer ◽  
Social Media ◽  
Metastatic Breast Cancer ◽  
Civil Rights ◽  
Early Stage ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Early Stage Disease ◽  
Stage Iv Breast Cancer

Dominant breast cancer narratives equate early detection and screening with “cure,” advocate for “awareness,” and identify women who undergo treatment for early stage disease as “survivors.” Left out of these narratives are the “metavivors”: women and men diagnosed with “incurable” metastatic breast cancer, also known as Stage IV. This article uses case studies to profile four women living with metastatic breast cancer who turn to social media to tell their stories: Sally, a former civil rights attorney turned breast cancer activist, who uses social media platforms to organize and mobilize Stage IV patients to advocate on their own behalf; Jane, who plows through databases of dense medical research to find treatments to save her own life; Jenny, a young mother dying of metastatic breast cancer who shares her experiences on a YouTube channel; and Grace, who participates in an early-stage clinical trial that she believes “cured” her, a term eschewed by both the medical establishment and fellow metavivors.

Phase II trial of neoadjuvant exemestane [EXE] and celecoxib [CELE] in breast cancer: Results of biomarkers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11056-11056 ◽  
Author(s):  
C. L. Shapiro ◽  
S. P. Povoski ◽  
R. Jiminez ◽  
J. Dehart ◽  
S. Ottman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Core Biopsy ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Small Sample ◽  
Rank Test ◽  
Ki 67 ◽  
Cancer History ◽  
Cox 2 ◽  
Tumor Measurements

11056 Background: Aromatase [CYP19] activity and expression is increased by prostaglandin E2, thus providing a rational for combining the COX-2 inhibitor, CELE, with an aromatase inhibitor. To evaluate the effects of these drugs on proliferation and other biomarkers, we conducted a neoadjuvant trial of EXE alone followed by the combination of EXE and CELE. The primary endpoint was the assessment of biomarkers and the secondary endpoint was toxicity. Methods: Clinical stages II/III, postmenopausal, estrogen [ER] and/or progesterone receptor [PR] positive, previously untreated, ECOG 0–1 were eligible. Excluded were inflammatory breast cancer, history of myocardial infarction, and documented allergy to aspirin, NSAIDs, or sulfonamides. After initial core biopsy pts received 8 weeks (wks) of EXE 25 mg daily. They then received a second core biopsy followed by 8 wks of EXE and CELE 400 mg twice daily. After 16 wks, pts had definitive surgery. Compliance was assessed by pill counts at study visists every 4 wks. At baseline, 8, and 16 wks, pts had tumor measurements by physical exam, mammogram, and ultrasound. A tissue microarray [TMA] was contructed and immunohistochemical [IHC] staining with commercially available antibodies for Ki-67, COX-2, HER-2, ER, and PR was performed. Two independent pathologists scored intensity and percentage of cells staining and were blinded to treatment and the timimg of specimen acquistion. Statistical analyses were performed using Wilcoxon signed-rank test Results: Twenty pts with a median age 62 (range 56–87) were enrolled. CELE was discontinued in 3 (15%) pts for grade 1 rash-1 pt; grade 1 creatinine elevation-1 pt; and grade 1 melena-1 pt. Three (15%) pts-partial response, 16 (80%)-stable disease, and 1 (5%)-progressive disease. None of the differences in biomarkers between 0 and 8 wks and 8 and 16 wks were significant. A trend toward decreasing mean Ki 67 was observed from 0 to 8 wks (20% vs 9%, p=0.19) and 8 to 16 wks (9% vs 7%, p=0.7) Conclusions: Neoadjuvant EXE followed by EXE/CELE was well tolerated with anti-tumor activity. Tumor cell proliferation decreased by about 50% during EXE, but small sample size precluded reaching statistical significance. Frozen tissue was collected and the results of CYP 19 mRNA expression will be presented. [Table: see text]

scholarly journals Female Breast Cancer in Suriname: Pathways to Treatment—A Patient’s Perception

2020 ◽  
Vol 6 (Supplement_1) ◽  
pp. 49-49
Author(s):  
Euridice R. Irving ◽  
Dennis R. A. Mans ◽  
Els Th. M. Dams ◽  
Maureen Y. Lichtveld
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
Access To Health Care ◽  
Early Stage ◽  
Diagnosis And Treatment ◽  
Related Factors ◽  
Entire Interval ◽  
Early Stage Disease ◽  
Resource Setting ◽  
Stage Disease

PURPOSE Delays across the entire cancer care continuum are not uncommon. This cross-sectional study explored the health care trajectories of Surinamese women with breast cancer and identified predictors of timely diagnosis and treatment initiation. METHODS One hundred women age 30 years or older who were newly diagnosed with breast cancer in 2017 to 2018 were recruited from all 4 hospitals in Paramaribo. Data on their demographics, lifestyle, reproductive and medical history, health status, and family history of breast cancer and other malignancies were collected using a validated semistructured questionnaire. Using Anderson’s Model of Pathways to Treatment, we defined a patient interval (from detection to first consultation), diagnostic interval (from consultation to histopathologic diagnosis), and treatment interval (from diagnosis to first treatment). Log-transformed data were analyzed using linear regression, and variables with P ≤ .05 were considered statistically significant predictors of intervals. RESULTS All participants had health insurance and access to health care. Eighty-five percent of patients presented with early-stage disease. Ninety percent of patients had self-detected their disease, with 70% finding a lump. Average age was 55.6 years (± 11.8 years). Median durations of patient, diagnostic, and treatment intervals were 13 days (interquartile, range, 4-63 days), 40 days (IQR, 21-57 days), and 18 days (IQR, 8-38 days), respectively. Median duration of the entire interval was 95 days (IQR, 59-272 days). Patient-related factors associated with the intervals were religion (β = −530; P = .003), being employed (β = 149.4; P = .007), and age 50 years and older (β = −195.8; P = .037). Disease-related factors were lump as first symptom (β = −175.6; P = .038) and late-stage disease at diagnosis (β = 213.5; P = .004). CONCLUSION Given the limited-resource setting, delays in Suriname’s health care can be minimized by programs aimed at increasing breast cancer awareness and education; however, delays may have been underestimated as a result of the over-representation of early-stage disease and recall bias regarding the first symptom detected.

scholarly journals Tumor Characteristics and Treatment Outcomes of Older Women with Breast Cancer in Jordan

2019 ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Fadwa Abdel Rahman ◽  
Hanan Al-Masri ◽  
Hazem Abdulelah ◽  
Mahmoud Abu Nasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Outcomes ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Early Stage ◽  
Poor Performance Status ◽  
Tumor Characteristics ◽  
Early Stage Disease ◽  
Node Positive ◽  
Stage Disease

Abstract Background : Less than 10% of newly diagnosed breast cancer in our region are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and have poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in such patients. Methods : Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients’ characteristics and treatment outcomes. Results : A total of 553 patients, median age 70 (range: 65-91) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), GIII in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P<0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P=0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P=0.048). Conclusions : Older Jordanian women with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Because of comorbidities and poor performance status, some patients were not aggressively treated.

Neuroendocrine differentiation in metastatic breast cancer following CDK 4/6 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13029-e13029
Author(s):  
Sakina Sekkate ◽  
Laure Ladrat ◽  
Christelle Pouliquen ◽  
Celine Callens ◽  
Jean Francois Geay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Aromatase Inhibitor ◽  
Neuroendocrine Differentiation ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Proliferation Index ◽  
Castration Resistant Prostate Cancer ◽  
Metastatic Tumors ◽  
Ki 67

e13029 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered as a standard of care based on the compelling data across all landmark trials. Methods: We report our experience about two cases with metastatic breast cancer treated by CDK4/6 inhibitor in combination with an aromatase inhibitor, which develop neuroendocrine differentiation. After observing an unusual massive progression, a biopsy of the metastasis was performed in both patients. Both histological analysis confirmed a lobular breast cancer with small cell neuroendocrine features and a high proliferation index (KI 67 90%). An NGS (Next generation sequencing) profile was realized on primary and metastatic tumors to detect new acquired genomic alterations. Results: The comparative analysis of the NGS results of primary and metastatic tumors revealed the occurrence of several events in both patients under treatment. For one patient, we identified new mutations in the genes CDH1, FANCG, PIK3CA, PTEN and TP53, which did not exist initially. For the second patient, we found an amplification of the segment containing FGFR1, CCND1, FGF4, FGF3, FADD genes and the deletion of the segment containing RB1 andTP53 genes. Such events were not observed on the primary tumor. Conclusions: Prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer but neuroendocrine differentiation is atypical in breast carcinoma. In case of unusual rapidly progressive disease after CDK4/6 inhibitor, biopsy of new metastases should be recommanded to search neuroendocrine differentiation, or druggable mutations to guide the treatment.

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