Impact of PIK3CA tumor mutation on the association of aspirin or NSAID use and time to breast cancer recurrence.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1521-1521 ◽  
Author(s):  
Anne Marie McCarthy ◽  
Wei He ◽  
Susan Regan ◽  
Andrew T. Chan ◽  
Beverly Moy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Pik3ca Mutation ◽  
Cancer Recurrence ◽  
Primary Diagnosis ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
N Use ◽  
Tumor Genotyping

1521 Background: Aspirin or NSAID (A/N) use post diagnosis is associated with lower risk of breast cancer recurrence and mortality in cohort studies. A potential mechanism is that A/Ns may suppress cell growth and induce apoptosis in tumors driven by phosphatidylinositol 3 kinase ( PIK3CA), the most common oncogene mutation in breast cancer. An interaction of A/Ns and PIK3CA mutation has been observed for colorectal cancer prognosis, but has not been studied in breast cancer. The objective was to assess time to breast cancer recurrence (TTR) with respect to A/N use and PIK3CAmutation. Methods: Patients with HR+/HER2- breast cancer treated at Massachusetts General Hospital in 2009-2014 who received tumor genotyping were included. PIK3CA mutations, including 8 common hotspot mutations, were assessed by a high-throughput tumor genotyping assay using DNA from formalin-fixed, paraffin-embedded tumor tissue. A/N use beginning 6 months post diagnosis through metastasis was extracted from electronic medical records using coded data and natural language processing. Patients with de novo metastatic disease or progressive disease within 6 months of primary diagnosis were excluded. TTR was estimated using Cox proportional hazards models. Results: Among breast cancer patients (N=212), 60 (28%) used A/Ns and 69 (33%) had PIK3CA mutation (see Table). After adjusting for age, stage, adjuvant endocrine therapy, radiation, and chemotherapy, A/N users had significantly longer TTR (HR=0.65 p=0.01). The association was similar for wild type (HR=0.58 p=0.01) and PIK3CA mutated tumors (HR=0.60 p=0.06), with no significant interaction of A/N use and PIK3CA (p=0.34). Conclusions: Among HR+ breast cancer patients, those who used A/Ns following primary diagnosis had longer TTR than non-users, regardless of tumor PIK3CA mutation status. The study provides a model for how tumor genomics could be integrated into secondary chemoprevention studies. [Table: see text]

scholarly journals 21-Gene Recurrence Assay Associated With Favorable Metabolic Profiles in HR-Positive, HER2-Negative Early-Stage Breast Cancer Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifei Zhu ◽  
Tiange Wang ◽  
Yiwei Tong ◽  
Xiaosong Chen ◽  
Kunwei Shen
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Cancer Patients ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Recurrence ◽  
Metabolic Profiles ◽  
Breast Cancer Patients ◽  
C Peptide

BackgroundComprehensive investigations of the associations between 21-gene recurrence assay and metabolic profiles in Chinese breast cancer patients are limited.MethodsWe evaluated the relations of the 21-gene recurrence risk score (RS) and the expression of cancer-related genes with metabolic factors and biomarkers of insulin and the insulin-like growth factor (IGF) axis, and examined the interactions between the 21-gene RS and these metabolic profiles on breast cancer recurrence in Chinese women with HR-positive, HER2-negative early-stage breast cancer.ResultsThe 21-gene RS was inversely associated with body mass index ([BMI]β: −0.178 kg/m2; P=0.040), the homeostasis model assessment of insulin resistance index ([HOMA-IR] β: −0.031; P=0.042), insulin (β: −0.036 uIU/ml; P=0.009), and C-peptide (β: −0.021 ug/L; P=0.014) and was positively associated with high-density lipoprotein cholesterol (β: 0.025 mmol/L; P=0.004), which were driven by the relation patterns between specific cancer-related genes and these metabolic profiles. Each 10-unit increase in the 21-gene RS was associated with 28% (95% CI: 5–47%) higher risk of breast cancer recurrence; this association was also observed in patients with favorable metabolic profiles in relevant to an absence of obesity, insulin resistance, hyperglycemia, hypertension, or dyslipidemia (28–44% higher risk) and among women with a low level of insulin, C-peptide, or the IGF1/IGFBP3 ratio (41–155% higher risk).ConclusionsThe 21-gene RS was related to favorable metabolic profiles including lower BMI, HOMA-IR, insulin, and C-peptide, and higher HDL in Chinese breast cancer patients, and its prognostic impact on breast cancer recurrence was more likely to present among patients with relatively favorable metabolic profiles.

scholarly journals Evaluating the Risk of Breast Cancer Recurrence and Metastasis After Adjuvant Tamoxifen Therapy by Integrating Polymorphisms in Cytochrome P450 Genes and Clinicopathological Characteristics

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Pang ◽  
Guoqiang Zhang ◽  
Na Yan ◽  
Jidong Lang ◽  
Yuebin Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cytochrome P450 ◽  
Cancer Patients ◽  
Cancer Recurrence ◽  
Clinicopathological Characteristics ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Risk Of Recurrence

Tamoxifen (TAM) is the most commonly used adjuvant endocrine drug for hormone receptor-positive (HR+) breast cancer patients. However, how to accurately evaluate the risk of breast cancer recurrence and metastasis after adjuvant TAM therapy is still a major concern. In recent years, many studies have shown that the clinical outcomes of TAM-treated breast cancer patients are influenced by the activity of some cytochrome P450 (CYP) enzymes that catalyze the formation of active TAM metabolites like endoxifen and 4-hydroxytamoxifen. In this study, we aimed to first develop and validate an algorithm combining polymorphisms in CYP genes and clinicopathological signatures to identify a subpopulation of breast cancer patients who might benefit most from TAM adjuvant therapy and meanwhile evaluate major risk factors related to TAM resistance. Specifically, a total of 256 patients with invasive breast cancer who received adjuvant endocrine therapy were selected. The genotypes at 10 loci from three TAM metabolism-related CYP genes were detected by time-of-flight mass spectrometry and multiplex long PCR. Combining the 10 loci with nine clinicopathological characteristics, we obtained 19 important features whose association with cancer recurrence was assessed by importance score via random forests. After that, a logistic regression model was trained to calculate TAM risk-of-recurrence score (TAM RORs), which is adopted to assess a patient’s risk of recurrence after TAM treatment. The sensitivity and specificity of the model in an independent test cohort were 86.67% and 64.56%, respectively. This study showed that breast cancer patients with high TAM RORs were less sensitive to TAM treatment and manifested more invasive characteristics, whereas those with low TAM RORs were highly sensitive to TAM treatment, and their conditions were stable during the follow-up period. There were some risk factors that had a significant effect on the efficacy of TAM. They were tissue classification (tumor Grade < 2 vs. Grade ≥ 2, p = 2.2e−16), the number of lymph node metastases (Node-Negative vs. Node < 4, p = 5.3e−07; Node < 4 vs. Node ≥ 4, p = 0.003; Node-Negative vs. Node ≥ 4, p = 7.2e−15), and the expression levels of estrogen receptor (ER) and progesterone receptor (PR) (ER < 50% vs. ER ≥ 50%, p = 1.3e−12; PR < 50% vs. PR ≥ 50%, p = 2.6e−08). The really remarkable thing is that different genotypes of CYP2D6*10(C188T) show significant differences in prediction function (CYP2D6*10 CC vs. TT, p < 0.019; CYP2D6*10 CT vs. TT, p < 0.037). There are more than 50% Chinese who have CYP2D6*10 mutation. So the genotype of CYP2D6*10(C188T) should be tested before TAM therapy.

scholarly journals Weight Gain, Metabolic Syndrome, and Breast Cancer Recurrence: Are Dietary Recommendations Supported by the Data?

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Colin E. Champ ◽  
Jeff S. Volek ◽  
Joshua Siglin ◽  
Lianjin Jin ◽  
Nicole L. Simone
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Weight Gain ◽  
Cancer Patients ◽  
Randomized Trials ◽  
Cancer Recurrence ◽  
Dietary Factors ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Long Term Outcome

Metabolic syndrome, which can include weight gain and central obesity, elevated serum insulin and glucose, and insulin resistance, has been strongly associated with breast cancer recurrence and worse outcomes after treatment. Epidemiologic and prospective data do not show conclusive evidence as to which dietary factors may be responsible for these results. Current strategies employ low-fat diets which emphasize supplementing calories with increased intake of fruit, grain, and vegetable carbohydrate sources. Although results thus far have been inconclusive, recent randomized trials employing markedly different dietary strategies in noncancer patients may hold the key to reducing multiple risk factors in metabolic syndrome simultaneously which may prove to increase the long-term outcome of breast cancer patients and decrease recurrences. Since weight gain after breast cancer treatment confers a poor prognosis and may increase recurrence rates, large-scale randomized trials are needed to evaluate appropriate dietary interventions for our breast cancer patients.

scholarly journals Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patients

2020 ◽  
Vol 25 (12) ◽  
pp. 3186-3197 ◽  
Author(s):  
Xuan Wang ◽  
Neng Wang ◽  
Lidan Zhong ◽  
Shengqi Wang ◽  
Yifeng Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Critical Role ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Depression And Anxiety ◽  
Breast Cancer Patients ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Cancer Specific Mortality

AbstractDepression and anxiety are common comorbidities in breast cancer patients. Whether depression and anxiety are associated with breast cancer progression or mortality is unclear. Herein, based on a systematic literature search, 17 eligible studies involving 282,203 breast cancer patients were included. The results showed that depression was associated with cancer recurrence [1.24 (1.07, 1.43)], all-cause mortality [1.30 (1.23, 1.36)], and cancer-specific mortality [1.29 (1.11, 1.49)]. However, anxiety was associated with recurrence [1.17 (1.02, 1.34)] and all-cause mortality [1.13 (1.07, 1.19)] but not with cancer-specific mortality [1.05 (0.82, 1.35)]. Comorbidity of depression and anxiety is associated with all-cause mortality [1.34 (1.24, 1.45)] and cancer-specific mortality [1.45 (1.11, 1.90)]. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety, being female and of younger age (<60 years), and shorter follow-up duration (≤5 years) were related to a poorer prognosis. Our study highlights the critical role of depression/anxiety as an independent factor in predicting breast cancer recurrence and survival. Further research should focus on a favorable strategy that works best to improve outcomes among breast cancer patients with mental disorders.

Concomitant CYP2D6 inhibitor use and tamoxifen adherence in early-stage breast cancer: A pharmacoepidemiologic study

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. CRA509-CRA509 ◽  
Author(s):  
V. Dezentje ◽  
N. J. Van Blijderveen ◽  
H. Gelderblom ◽  
H. Putter ◽  
M. P. Van Herk-Sukel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Cox Proportional Hazards Model ◽  
Breast Cancer Recurrence ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Cyp2d6 Inhibitors

CRA509 Background: The use of cytochrome P450 2D6 inhibiting drugs (CYP2D6 inhibitors) during tamoxifen treatment leads to a decrease in plasma concentration of endoxifen, the major active tamoxifen metabolite. Concomitant use of CYP2D6 inhibitors, such as the commonly prescribed selective serotonin reuptake inhibitors, as well as low tamoxifen adherence may negatively impact tamoxifen efficacy in breast cancer. The objectives were to relate concomitant CYP2D6 inhibitor use and tamoxifen adherence to breast cancer event free time (EFT). Methods: Data were used from PHARMO, a pharmacy database, PALGA, a nationwide pathology database and the Dutch Medical Register in the Netherlands. Breast cancer patients who were treated with tamoxifen as adjuvant therapy between 1994 and 2006 were included. A Cox proportional hazards model with a time-dependent definition for the CYP2D6 inhibitor exposure was used. Results: 1,990 breast cancer patients using tamoxifen were included, among whom 215 (10.8%) used a CYP2D6 inhibitor during tamoxifen treatment. No association between concomitant CYP2D6 inhibitor use and breast cancer recurrence was observed. Poor tamoxifen adherence was associated with lower EFT. Conclusions: This observational study did not show an association between concomitant CYP2D6 inhibitor use and breast cancer recurrence among patients treated with adjuvant tamoxifen. However, this study shows for the first time that poor tamoxifen adherence is associated with lower EFT. No significant financial relationships to disclose.

Safety and tolerability of the dual PI3K/mTOR inhibitor LY3023414 in combination with fulvestrant in treatment refractory advanced breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1064-1064 ◽  
Author(s):  
Anna M. Varghese ◽  
Kathleen N. Moore ◽  
Erika Paige Hamilton ◽  
David Michael Hyman ◽  
Komal L. Jhaveri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Partial Response ◽  
Cancer Patients ◽  
Oral Mucositis ◽  
Phase 1 ◽  
Pik3ca Mutation ◽  
Mucosal Inflammation ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
Biomarker Analysis

1064 Background: Thephosphatidylinositol 3-kinase (PI3K) /mammalian target of rapamycin (mTOR) pathway is frequently activated in breast cancer. LY3023414 (LY) is an oral ATP- competitive inhibitor that selectively and potently inhibits class I PI3K isoforms, mTOR, and DNA-PK. The recommended phase 2 dose (RP2D) of LY monotherapy was previously established to be 200 mg twice daily (BID). Here we present the safety and preliminary activity data of LY in combination with fulvestrant (F) for breast cancer patients (pts) as part of a multi-cohort Phase 1 study. Methods: Pts with advanced HR+, HER2- breast cancer refractory to standard treatment received 200 mg LY BID + 500 mg F (day 1 and 15, then once monthly). Eligible pts had measurable disease and baseline tumor tissue available. Primary objective was to determine a RP2D. Other objectives included assessment of pharmacokinetics (PK), antitumor activity, and biomarker analysis. Results: 9 pts received LY + F in the breast cancer expansion cohort. All pts had multiple lines of prior systemic therapy (range 3-12), including chemotherapy. Dose limiting toxicity was observed in one pt in the form of grade (Gr) 3 oral mucositis. Common possibly related adverse events included nausea (5 pts), vomiting (4 pts), oral mucositis (4 pts), decreased appetite (3 pts), fatigue (3 pts), mucosal inflammation (2 pts), and paresthesia (2 pts). No obvious impact of LY on F PK or of F on LY PK was observed. Median duration of treatment was 15 weeks (range 3-63). In the 6 pts evaluable for tumor response, there was 1 durable partial response according to RECIST (still on treatment for ≥11 months) and 4 further pts had a decrease in their target lesions for a disease control rate of 56%. The median progression-free survival for this cohort is 4.2 months (90% CI 1.8, NA). Of note, the partial response was observed in a pt harboring an activating PIK3CA mutation (H1047R). Further biomarker analysis is ongoing. Conclusions: The RP2D of LY in combination with F is 200mg BID and may cause tumor regression or stabilization in breast cancer pts. Clinical trial information: NCT01655225.

scholarly journals Proteomic Analysis of Inflammatory Biomarkers Associated With Breast Cancer Recurrence

2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 669-675 ◽  
Author(s):  
Alakesh Bera ◽  
Eric Russ ◽  
Muthu Srinivasan ◽  
Ofer Eidelman ◽  
Michael Eklund ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Imaging ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cancer Recurrence ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Recurrent Breast

ABSTRACT Introduction Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer. Materials and Method: In this study, we analyzed serum samples from both recurrent and nonrecurrent breast cancer patients by different proteomics methods to identify biomarkers in patients with recurrence of disease. Results Comparative data analysis identified several histone deacetylase (HDAC) proteins, which were found at significantly higher levels in the serum of recurrent breast cancer patients: HDAC9 (C-term) (P = 0.0035), HDAC5 (C-term) (P = 0.013), small ubiquitin-like modifier 1 (N-term) (P = 0.017), embryonic stem cell-expressed Ras (inter) (P = 0.018), and HDAC7 (C-term) (P = 0.020). Chronic inflammation plays a critical role in the development of the breast cancer recurrence, and we identified several proinflammatory cytokines that were present at elevated levels only in recurrent breast cancer patient serum. Conclusions Our data indicated that the epigenetic regulation of inflammatory processes plays a critical role in breast cancer recurrence. The identified proteins could lay the groundwork for the development of a serum-based breast cancer recurrence assay.

scholarly journals Pathologic Complete Response and Its Impact on Breast Cancer Recurrence and Patient’s Survival after Neoadjuvant Therapy: A Comprehensive Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hui Liu ◽  
Liqiong Lv ◽  
Hui Gao ◽  
Ming Cheng
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Cancer Recurrence ◽  
Complete Response ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Her2 Positive

Objective. Earlier research has illustrated prognostic significance of pathologic complete response (pCR) in neoadjuvant therapy (NAT) for breast cancer, whereas correlation between treatment after achieving pCR and survival improvement remains underexplored. We attempted to measure the relation between pCR achieved after NAT and breast cancer recurrence or patient’s survival. Methods. We searched PubMed, EMBASE, Web of Science, and The Cochrane Library databases to find relevant articles from their inception to November 2020. According to eligibility criteria, studies were selected and basic data were extracted. The primary endpoint was the correlation between pCR achieved after NAT and event-free survival (EFS) or overall survival (OS). The results were obtained by directly extracting specific information from the literature or estimating individual data by survival curves on DigitizeIt software, presented with HR and 95% CI. All data were processed on Stata 14.0 software. Results. Among 4338 articles, there were 25 eligible articles involving 8767 patients. The EFS of patients achieved pCR after NAT improved obviously ( HR = 0.27 ; 95% CI, 0.24-0.31), especially in triple negative ( HR = 0.17 ; 95% CI, 0.12-0.24) and HER2 positive ( HR = 0.24 ; 95% CI, 0.20-0.30) breast cancer patients. As such, pCR after NAT was implicated in significantly increased OS ( HR = 0.32 ; 95% CI, 0.27–0.37). Conclusion. Achieving pCR after NAT was notably related to the improvement of EFS and OS, especially for patients with triple-negative and HER2-positive breast cancer. pCR can be a surrogate indicator for outcome of breast cancer patients after NAT, as well as a predictor of treatment efficacy after NAT. Besides, well-designed studies are still warranted for confirmation.

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