Dataset Information

Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.

ABSTRACT:

Background

Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS).

Materials and methods

A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A included non-diabetic MBC patients treated with metformin in conjunction with chemotherapy and group B included those treated with chemotherapy alone. Both PFS and RR were used as a criteria to evaluate the treatment outcome. Associated adverse effects of metformin were also assessed.

Results

The average age of the participants in group A and group B was 50 vs. 47.5, respectively. No significant differences were detected between both cohorts concerning RR levels (regression disease (RD) 27.8% vs. 12.5%, stationary disease (SD) 44.4% vs. 41.7%, progression disease (PD) 27.8% vs. 45.8%, respectively, p = 0.074). Moreover, PFS showed no significant difference between both groups (p = 0.753). There was no significant correlation between metformin concentration and their adverse effects on the study participants.

Conclusion

Metformin as an adjuvant therapy to MBC undergoing chemotherapy showed no significant survival benefit as determined by RR and PFS.

SUBMITTER: Essa NM

PROVIDER: S-EPMC9572354 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.

Essa Nourhan M NM Salem Heba F HF Elgendy Marwa O MO Gabr A A Omran Mervat M MM Hassan Nivin A NA Tashkandi Hanaa M HM Harakeh Steve S Boshra Marian S MS

Journal of clinical medicine 20220920 19

<h4>Background</h4>Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS).<h4>Materials and methods</h4>A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A includ ...[more]

PMID: 36233373

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Project description:BackgroundTreatment for triple-negative breast cancer (TNBC) remains a significant challenge due to a lack of targeted therapies. While photodynamic therapy (PDT) has been utilized as a treatment approach for several types of cancer, oxyphotodynamic therapy (OPDT) is a novel method that improves treatment efficacy by increasing local oxygen concentration. Metformin (MET) has been demonstrated utility as an anti-tumor agent by acting through the adenosine monophosphate-activated protein kinase (AMPK) pathway. We hypothesized that MET in combination with heme, a byproduct of 5-aminolevulinic acid (ALA), may increase cytotoxicity for cancer treatment. This study aimed to investigate the synergistic effect of MET and ALA with PDT or OPDT on TNBC tumorigenic cells.MethodsThe treatment efficacy and phototoxicity of PDT or OPDT were determined using a cell viability assay. PDT/OPDT experiments were carried out in nine groups based on different combinations and concentrations of ALA and/or MET. To calculate the synergistic effect by compuSyn soft for different groups, cells were incubated with ALA and/or MET at the following concentrations (0, 0.25, 0.5,1, 2, 4, 8, 16, 24, and 32 mM). The fluorescence of ALA-induced protoporphyrin IX (PpIX) and MitoTracker Green were observed under a confocal microscope.ResultsThe optimized therapeutic concentration ratio of ALA and MET was determined to be 1:1. The inhibition of cancer growth (IC50) for each group was 14.03, 10.62, 7.71, 18.27, 22.09, 23.96, 4.57, 10.20, and 8.18 mM, respectively. The combination index (CI) values (fa =0.5) of the last three combination groups (groups 7, 8, and 9) were 0.44, 1.70, and 1.47, respectively. PpIX fluorescence intensity of group 9 (ALA-MET-OPDT group) remained the highest among all groups, indicating an enhanced therapeutic effect.ConclusionsThis study introduces OPDT as a novel anti-tumor therapy for TNBC. Furthermore, the combined use of ALA and MET had a synergistic anti-tumor effect in TNBC cells when combined with OPDT.

Project description:BACKGROUND:In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS:Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS:In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS:Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).

Dataset Information

Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.

Background

Materials and methods

Results

Conclusion

Publications

Efficacy of Metformin as Adjuvant Therapy in Metastatic Breast Cancer Treatment.

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