Adherence to tamoxifen in Mexican young women with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12003-e12003
Author(s):  
Cynthia Mayte Villarreal-Garza ◽  
Bertha Alejandra Martinez-Cannon ◽  
Andrea Castro-Sanchez ◽  
Alejandra Platas ◽  
Alan Fonseca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Significant Proportion ◽  
Medication Possession Ratio ◽  
Hormonal Treatment ◽  
Recurrence Risk ◽  
Young Group ◽  
Long Term Effects ◽  
Increased Risk ◽  
Adherence Data

e12003 Background: Young age has been associated with significantly increased risk of breast cancer (BC) death among women with luminal BC. One contributing factor might be the low rate of tamoxifen (TMX) adherence previously reported in this young group. Given that in Mexico a disproportionate rate of BC is diagnosed among YW, information regarding TMX adherence is particularly relevant. Our study's aim was to report TMX adherence in Mexican YW and its associated determinants. Methods: Consecutive patients ≤40y at diagnosis at the National Cancer Institute in Mexico City, under TMX treatment, completed a multiple-choice survey regarding the use and attitudes about hormonal therapy and adherence. Data of TMX disposal was collected from the pharmacy’s records, and the medication possession ratio (MPR) was calculated; an MPR ≥80% was considered adherent. Results: 135 YW with a median age at diagnosis of 35.7y (24-40) were included. 77% were undergraduate, 28% unpaired and 33% childless. Median follow-up was 26 months. 95% of patients reported a regular TMX intake: 70% did not miss any doses, while 25% missed 1-6 doses a month. Only 45% considered that the information received regarding TMX therapy was sufficient and for 37% was incomprehensive. 43% thought TMX significantly reduced their recurrence-risk and 60% strongly believed that they needed to be on TMX treatment. 73% of women reported adverse effects, being menopausal symptoms the most frequent, but only 27% were worried about the treatment long-term effects. From the 99 patients with a pharmacy record, 73% had an MPR > 80%. No significant factor was statistically associated with TMX adherence. Conclusions: Although Mexican YW and pharmacy data surprisingly sustained higher rates of TMX adherence compared to previous data, still a significant proportion of patients were non-adherent. Two-thirds of our patients reported having adverse effects, which might contribute to late TMX discontinuation. Since the newer recommendations of double hormonal blockade could lead to higher withdrawal rates of endocrine therapy in YW, adherence should be emphasized and closely monitored. Accordingly, hormonal treatment adherence should be a key component in the medical assessment of young luminal BC patients.

scholarly journals Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2415 ◽  
Author(s):  
Daniele Fanale ◽  
Lorena Incorvaia ◽  
Clarissa Filorizzo ◽  
Marco Bono ◽  
Alessia Fiorino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Bilateral Breast Cancer ◽  
Significant Proportion ◽  
Susceptibility Genes ◽  
Gene Panel ◽  
Panel Testing ◽  
Cancer Susceptibility Genes ◽  
Gene Panel Testing ◽  
Increased Risk

Patients with unilateral breast cancer (UBC) have an increased risk of developing bilateral breast cancer (BBC). The annual risk of contralateral BC is about 0.5%, but increases by up to 3% in BRCA1 or BRCA2 pathogenic variant (PV) carriers. Our study was aimed to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless their cancer family history and age at diagnosis. We retrospectively collected all clinical information of 139 BBC patients genetically tested for germline PVs in different cancer susceptibility genes by NGS-based multi-gene panel testing. Our investigation revealed that 52 (37.4%) out of 139 BBC patients harbored germline PVs in high- and intermediate-penetrance breast cancer (BC) susceptibility genes including BRCA1, BRCA2, PTEN, PALB2, CHEK2, ATM, RAD51C. Nineteen out of 53 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.4%) of PVs would have been lost. Therefore, offering a NGS-based multi-gene panel testing to all BBC patients may significantly increase the detection rates of germline PVs in other cancer susceptibility genes beyond BRCA1/2, avoiding underestimation of the number of individuals affected by a hereditary tumor syndrome.

Abstract Submission

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Free Survival ◽  
Increased Risk

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]

Direct and indirect economic evaluation of upfront and sequential adjuvant treatment in postmenopausal women with breast cancer based on the BIG 1–98 trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6594-6594
Author(s):  
C. Skedgel ◽  
D. Rayson ◽  
T. Younis
Keyword(s):  
Breast Cancer ◽  
Economic Evaluation ◽  
Postmenopausal Women ◽  
Indirect Comparison ◽  
Cost Savings ◽  
Hormonal Treatment ◽  
Recurrence Risk ◽  
Quality Adjusted Life Year ◽  
Sensitivity Analyses ◽  
Carry Over

6594 Background: The monotherapy arms of the BIG 1–98 trial established the clinical superiority of upfront letrozole (LET) relative to tamoxifen alone (TAM) but direct comparison of sequential TAM-LET, LET-TAM and upfront LET did not establish a clinically superior strategy. We undertook an economic evaluation to identify an economically preferred strategy based on the relative cost-effectiveness (CE) of TAM, LET, TAM-LET, and LET-TAM in terms of cost per quality-adjusted life year gained (QALYG). Methods: A state-transition model was developed to calculate cumulative costs and QALYs over a 25yr horizon for hypothetical cohorts of postmenopausal women with HR+ breast cancer undergoing adjuvant hormonal treatment. As the sequential arms were not directly compared to TAM alone, it was not possible to directly compare all strategies. As such, the analysis conducted direct within-arm comparisons and an indirect between-arm comparison. DFS endpoints and relative DFS benefit were derived from the monotherapy and sequential arms of BIG 1–98. Adverse events were not included as these have not yet been reported. Sensitivity analyses were conducted for the key parameters and assumptions, including the baseline recurrence risk and the duration of carry-over benefit. Costs and utility weights were derived from the literature. The analysis took a Canadian direct payer perspective and drug costs were based on 2008 Canadian average wholesale prices. Costs and outcomes were discounted at 3%. Results: In the monotherapy arms LET had a CE of $16,650 relative to TAM. In the sequential arms LET-TAM had superior QALYGs and cost savings relative to LET and TAM-LET. In economic terms, LET-TAM dominated LET and TAM-LET. In the indirect comparison, LET-TAM dominated LET and TAM-LET and had superior QALYGs at increased cost relative to TAM for a CE of $178. Conclusions: Direct comparisons confirm the economic favourability of LET relative to TAM and establish the dominance of LET-TAM over LET and TAM-LET. These indirect comparisons support the strong economic favourability of LET-TAM relative to TAM in the indirect comparison. In the absence of superior clinical outcomes, economic evaluation is a useful in suggesting a preferred strategy. No significant financial relationships to disclose.

scholarly journals Germline APOBEC3B deletion in Asian women increases somatic hypermutation in breast cancer that is associated with Her2 subtype, PIK3CA mutations, immune activation, and increased survival

2020 ◽  
Author(s):  
Jia-Wern Pan ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Boon-Keat Chong ◽  
Mei-Yee Meng ◽  
Pei-Sze Ng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Activation ◽  
Somatic Hypermutation ◽  
Molecular Subtype ◽  
Significant Proportion ◽  
Asian Women ◽  
Breast Cancers ◽  
Coding Region ◽  
Deletion Polymorphism ◽  
Increased Risk

AbstractA 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian compared to European descent. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3’UTR, and is associated with an increased risk for breast cancer in Asian women. Here, we explored the relationship between the A3B deletion polymorphism with tumour characteristics in Asian women. Using whole exome and whole transcriptome sequencing data of 527 breast tumours, we report that germline A3B deletion polymorphism leads to expression of the A3A-B hybrid isoform and increased APOBEC-associated somatic hypermutation. Hypermutated tumours, regardless of A3B germline status, were associated with the Her2 molecular subtype and PIK3CA mutations. Compared to non-hypermutated tumours, hypermutated tumours also had higher neoantigen burden, tumour heterogeneity and immune activation. Taken together, our results suggest that the germline A3B deletion polymorphism, via the A3A-B hybrid isoform, contributes to APOBEC-mutagenesis in a significant proportion of Asian breast cancers. In addition, APOBEC somatic hypermutation, regardless of A3B background, may be an important clinical biomarker for Asian breast cancers.Graphical Abstract

scholarly journals Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer

2015 ◽  
Vol 33 (20) ◽  
pp. 2262-2269 ◽  
Author(s):  
Wei He ◽  
Fang Fang ◽  
Catherine Varnum ◽  
Mikael Eriksson ◽  
Per Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Replacement ◽  
Hormonal Treatment ◽  
Linkage Study ◽  
Adjuvant Hormone Therapy ◽  
Breast Cancer Outcomes ◽  
Drug Register ◽  
Increased Risk

Purpose To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. Patients and Methods We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395). Results Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (≥ 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (≥ 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years. Conclusion Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes.

Risk of gastrointestinal and hepatic toxicities in patients with hormone receptor-positive HER2-negative breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis of randomized controlled trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18284-e18284
Author(s):  
Aung Tun ◽  
Kyaw Zin Thein ◽  
Yu Yu Thar ◽  
Asha Nayak ◽  
Elizabeth Guevara
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
High Grade ◽  
Randomized Controlled ◽  
Hormone Receptor Positive ◽  
Relative Risks ◽  
Increased Risk

e18284 Background: CDK4/6 inhibitors are proven to be beneficial in patients with hormone receptor-positive HER2-negative breast cancer. Studies have suggested an increased risk of gastrointestinal (GI) events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the risk of GI and hepatic toxicities. Methods: We systematically conducted a comprehensive literature search using MEDLINE and EMBASE databases through January 1, 2017. RCTs that mention GI symptoms and/or elevation of liver enzymes as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% confidence interval (CI). Results: Five RCTs with a total of 2021 patients were eligible for analysis. The study arm used palbociclib-letrozole, palbociclib-fulvestrant, and ribociclib-letrozole while the control arm used placebo with letrozole or fulvestrant. The relative risks of all-grade elevated AST was 2.6 (95% CI: 1.15–5.86; p = 0.02); all-grade elevated ALT: 2.82 (95% CI: 1.25–6.36; p = 0.01); all-grade stomatitis: 3.32 (95% CI: 2.09-5.28; p < 0000.1); all-grade nausea: 1.79 (95%CI: 1.25-2.58; p = 0.002); all-grade vomiting:1.55 (95% CI: 0.92-2.63; p = 0.10); and all-grade diarrhea: 1.59 (95% CI 1.28-1.98; p < 0.0001). The relative risks of high-grade elevated AST was 3.08 (95% CI: 1.42–6.67; p = 0.004); high-grade elevated ALT: 7.2 (95% CI: 2.81–18.43; p < 0.0001); high-grade stomatitis: 2.01 (95% CI: 0.22-18.02; p = 0.53); high-grade nausea: 0.76 (95%CI: 0.12-4.78; p = 0.77); high-grade vomiting: 0.88 (95% CI: 0.19-4.13; p = 0.87); and high-grade diarrhea: 1.23 (95% CI 0.52-2.92; p = 0.64). Conclusions: Our meta-analysis demonstrated that CDK 4/6 inhibitor-based regimens are associated with a higher risk of all-grade and high-grade elevated AST and ALT. Moreover, the regimen is associated with increased risk of all-grade stomatitis, nausea and diarrhea. Recognizing these adverse effects may help clinicians in delivering proper supportive care and thereby enhancing patients’ quality of life.

scholarly journals Breast Cancer Recurrence Risk Assessment: Is Non-Invasive Monitoring an Option?

2018 ◽  
Vol 3 (3) ◽  
pp. 1-17 ◽  
Author(s):  
Elisa M. Schunkert ◽  
Wanzhou  Zhao ◽  
Kurt Zänker
Keyword(s):  
Breast Cancer ◽  
Risk Assessment ◽  
Locally Advanced ◽  
Cancer Recurrence ◽  
Recurrence Risk ◽  
Breast Cancer Recurrence ◽  
Invasive Monitoring ◽  
Non Invasive ◽  
Increased Risk

Background: Metastatic breast cancer (MBC) represents a life-threatening disease with a median survival time of 18–24 months that often can only be treated palliatively. The majority of women suffering from MBC are those who had been previously diagnosed with locally advanced disease and subsequently experienced cancer recurrence in the form of metastasis. However, according to guidelines, no systemic follow-up for monitoring purposes is recommended for these women. The purpose of this article is to review current methods of recurrent risk assessment as well as non-invasive monitoring options for women at risk for distant disease relapse and metastasis formation. Methods: We used PubMed and national guidelines, such as the National Comprehensive Cancer Network (NCCN), to find recently published studies on breast cancer recurrence risk assessment and systemic monitoring of breast cancer patients through non-invasive means. Results: The options for recurrence risk assessment of locally invasive breast cancer has improved due to diverse genetic tests, such as Oncotype DX, MammaPrint, the PAM50 (now known as the “Prosigna Test”) assay, EndoPredict (EP), and the Breast Cancer Index (BCI), which evaluate a women’s risk of relapse according to certain cancer-gene expression patterns. Different promising non-invasive urinary protein-based biomarkers with metastasis surveillance potential that have been identified are MMP-2, MMP-9, NGAL, and ADAM12. In particular, ααCTX, ββCTX, and NTX could help to monitor bone metastasis. Conclusion: In times of improved recurrence risk assessment of women with breast cancer, non-invasive biomarkers are urgently needed as potential monitoring options for women who have an increased risk of recurrence. Urine as a bioliquid of choice provides several advantages – it is non-invasive, can be obtained easily and frequently, and is economical. Promising biomarkers that could help to follow up women with increased recurrence risk have been identified. In order for them to be implemented in clinical usage and national guideline recommendations, further validation in larger independent cohorts will be needed.

Decreased Risk of Stroke Among 10-Year Survivors of Breast Cancer

2006 ◽  
Vol 24 (34) ◽  
pp. 5388-5394 ◽  
Author(s):  
Maartje J. Hooning ◽  
Lucille D.A. Dorresteijn ◽  
Berthe M.P. Aleman ◽  
Arnoud C. Kappelle ◽  
Jan G.M. Klijn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Proportional Hazards ◽  
Hormonal Treatment ◽  
Cox Proportional Hazards ◽  
Radiation Fields ◽  
Cerebrovascular Events ◽  
Increased Risk ◽  
Internal Mammary

Purpose To assess treatment-specific risk of cerebrovascular events in early breast cancer (BC) patients, accounting for cerebrovascular risk factors. Patients and Methods We studied the incidence of cerebrovascular accidents (CVA; stroke and transient ischemic attack [TIA]) in 10-year survivors of early BC (n = 4,414) treated from 1970 to 1986. Follow-up was 96% complete until January 2000. Treatment-specific incidence of CVA was evaluated by standardized incidence ratios (SIRs) based on comparison with general population rates and by Cox proportional hazards regression. Results After a median follow-up of 18 years, 164 strokes and 109 TIAs were observed, resulting in decreased SIRs of 0.8 (95% CI, 0.6 to 0.9) for stroke and 0.8 (95% CI, 0.7 to 1.0) for TIA. Significantly increased risk of stroke was found in women who had received hormonal treatment (HT; tamoxifen) and in women who had hypertension or hypercholesterolemia, with hazard ratios (HRs) of 1.9, 2.1, and 1.6, respectively. Patients irradiated on the supraclavicular area and/or internal mammary chain (IMC) did not experience a higher risk of stroke (HR = 1.0; 95% CI, 0.7 to 1.6) or TIA (HR = 1.4; 95% CI, 0.9 to 2.5) compared with patients who did not receive radiotherapy or who were irradiated on fields other than the supraclavicular area or IMC. Conclusion Long-term survivors of BC experience no increased risk of cerebrovascular events compared with the general population. HT is associated with an increased risk of stroke. Radiation fields including the carotid artery do not seem to increase the risk of stroke compared with other fields.

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