Body fatness and mTOR pathway activation of breast cancer in the Women’s Circle of Health Study

Abstract Energy imbalance has an important role in breast cancer prognosis. Hyperactive mechanistic Target of Rapamycin (mTOR) pathway is associated with breast tumor growth, but the extent to which body fatness is associated with mTOR pathway activities in breast cancer is unclear. We performed immunostaining for mTOR, phosphorylated (p)-mTOR, p-AKT, and p-p70S6K in tumor tissue from 590 women (464 African Americans/Blacks and 126 Whites) with newly diagnosed invasive breast cancer in the Women’s Circle of Health Study. Anthropometric measures were taken by study staff, and body composition was measured by bioelectrical impedance analysis. Linear regressions were used to estimate percent differences in protein expression between categories of body mass index (BMI), waist circumference, waist/hip ratio, fat mass, fat mass index, and percent body fat. We observed that BMI ≥ 35.0 vs. <25 kg/m2 was associated with 108.3% (95% CI = 16.9%–270.9%) and 101.8% (95% CI = 17.0%–248.8%) higher expression in p-mTOR and normalized p-mTOR, i.e., p-mTOR/mTOR, respectively. Quartiles 4 vs. 1 of waist/hip ratio was associated with 41.8% (95% CI = 5.81%–89.9%) higher mTOR expression. Similar associations were observed for the body fat measurements, particularly in patients with estrogen receptor-negative (ER−) tumors, but not in those with ER+ tumors, although the differences in associations were not significant. This tumor-based study found positive associations between body fatness and mTOR pathway activation, evident by a p-mTOR expression, in breast cancer. Our findings suggest that mTOR inhibition can be a treatment strategy to prevent the recurrence of these tumors in obese individuals.

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Inhibition of the PI3K/mTOR Pathway in Breast Cancer to Enhance Response to Immune Checkpoint Inhibitors in Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22105207 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5207

Author(s):

Chi Yan ◽

Jinming Yang ◽

Nabil Saleh ◽

Sheau-Chiann Chen ◽

Gregory D. Ayers ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

Tumor Growth ◽

Cd8 T Cells ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Mtor Pathway ◽

Complete Regression ◽

Mtor Inhibition

Objectives: Inhibition of the PI3K/mTOR pathway suppresses breast cancer (BC) growth, enhances anti-tumor immune responses, and works synergistically with immune checkpoint inhibitors (ICI). The objective here was to identify a subclass of PI3K inhibitors that, when combined with paclitaxel, is effective in enhancing response to ICI. Methods: C57BL/6 mice were orthotopically implanted with syngeneic luminal/triple-negative-like PyMT cells exhibiting high endogenous PI3K activity. Tumor growth in response to treatment with anti-PD-1 + anti-CTLA-4 (ICI), paclitaxel (PTX), and either the PI3Kα-specific inhibitor alpelisib, the pan-PI3K inhibitor copanlisib, or the broad spectrum PI3K/mTOR inhibitor gedatolisib was evaluated in reference to monotherapy or combinations of these therapies. Effects of these therapeutics on intratumoral immune populations were determined by multicolor FACS. Results: Treatment with alpelisib + PTX inhibited PyMT tumor growth and increased tumor-infiltrating granulocytes but did not significantly affect the number of tumor-infiltrating CD8+ T cells and did not synergize with ICI. Copanlisib + PTX + ICI significantly inhibited PyMT growth and increased activation of intratumoral CD8+ T cells as compared to ICI alone, yet did not inhibit tumor growth more than ICI alone. In contrast, gedatolisib + ICI resulted in significantly greater inhibition of tumor growth compared to ICI alone and induced durable dendritic-cell, CD8+ T-cell, and NK-cell responses. Adding PTX to this regimen yielded complete regression in 60% of tumors. Conclusion: PI3K/mTOR inhibition plus PTX heightens response to ICI and may provide a viable therapeutic approach for treatment of metastatic BC.

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Seasonal and Longitudinal Changes in Body Composition by Sport-Position in NCAA Division I Basketball Athletes

Sports ◽

10.3390/sports6030085 ◽

2018 ◽

Vol 6 (3) ◽

pp. 85 ◽

Cited By ~ 5

Author(s):

Jennifer Fields ◽

Justin Merrigan ◽

Jason White ◽

Margaret Jones

Keyword(s):

Body Composition ◽

Body Mass ◽

Body Fat ◽

Fat Mass ◽

Ncaa Division I ◽

The Body ◽

Fat Free Mass ◽

Strength And Conditioning ◽

Air Displacement Plethysmography ◽

Within Subjects

The purpose of this study was to assess the body composition of male and female basketball athletes (n = 323) across season, year, and sport-position using air displacement plethysmography. An independent sample t-test assessed sport-position differences. An analysis of variance was used to assess within-subjects across season (pre-season, in-season, and off-season), and academic year (freshman, sophomore, and junior). For both men and women basketball (MBB, WBB) athletes, guards had the lowest body fat, fat mass, fat free mass, and body mass. No seasonal differences were observed in MBB, but following in-season play for WBB, a reduction of (p = 0.03) in fat free mass (FFM) was observed. Across years, MBB showed an increase in FFM from freshman to sophomore year, yet remained unchanged through junior year. For WBB across years, no differences occurred for body mass (BM), body fat (BF%), and fat mass (FM), yet FFM increased from sophomore to junior year (p = 0.009). Sport-position differences exist in MBB and WBB: Guards were found to be smaller and leaner than forwards. Due to the importance of body composition (BC) on athletic performance, along with seasonal and longitudinal shifts in BC, strength and conditioning practitioners should periodically assess athletes BC to ensure preservation of FFM. Training and nutrition programming can then be adjusted in response to changes in BC.

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Prevalence of obesity using the body mass index and equivalent age- and sex-specific thresholds for percentage body fat mass

Obesity Research & Clinical Practice ◽

10.1016/j.orcp.2013.12.668 ◽

2013 ◽

Vol 7 ◽

pp. e93

Author(s):

Julie A. Pasco ◽

Haslinda Gould ◽

Kara L. Holloway ◽

Amelia G. Dobbins ◽

Mark A. Kotowicz ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Body Fat ◽

Fat Mass ◽

The Body ◽

Body Fat Mass ◽

Percentage Body Fat ◽

Equivalent Age ◽

Prevalence Of Obesity ◽

Age And Sex

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pAKT pathway activation is associated with PIK3CA mutations and good prognosis in luminal breast cancer in contrast to p-mTOR pathway activation

npj Breast Cancer ◽

10.1038/s41523-019-0102-1 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Amir Sonnenblick ◽

David Venet ◽

Sylvain Brohée ◽

Noam Pondé ◽

Christos Sotiriou

Keyword(s):

Breast Cancer ◽

Good Prognosis ◽

Mtor Pathway ◽

Luminal Breast Cancer ◽

Pik3ca Mutations ◽

Pathway Activation

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Changes in Body Fat Distribution in Antiretroviral-Naive HIV-Positive Individuals Initiating Current ART Regimens

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01489 ◽

2018 ◽

Vol 104 (3) ◽

pp. 900-905 ◽

Cited By ~ 1

Author(s):

Juan Tiraboschi ◽

Antonio Navarro-Alcaraz ◽

Dolors Giralt ◽

Carmen Gomez-Vaquero ◽

Maria Saumoy ◽

...

Keyword(s):

Body Mass ◽

Body Fat ◽

Fat Mass ◽

Fat Distribution ◽

Body Fat Distribution ◽

The Body ◽

Strand Transfer ◽

Mass Ratio ◽

Total Fat ◽

Fat Mass Ratio

Abstract Objectives To describe the changes in body fat distribution (BFD) occurring over 60 months in a group of antiretroviral therapy (ART)-naive individuals starting different antiretroviral regimens. Methods A prospective ongoing fat change assessment including clinical evaluation and dual X-ray absorptiometry scan is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk, and total fat as well as fat mass ratio were determined. Results A total of 146 patients were included (80% male, 40% MSM). Mean age was 44 years, HIV-1 RNA was 4.98 log10 copies/mL, and CD4 count was 254 cells/μL. The most common initial antiretroviral combination included non-nucleoside reverse transcription inhibitor (NNRTI) drugs followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI)-based regimens. At month 36, an increase was seen in the body mass index (BMI), total fat, trunk fat, and limb fat. The fat mass ratio (FMR) also showed a significant increase in both men and women (P = 0.001). In patients receiving NNRTI- or INSTI-based regimens (but not PIs), there was a marginal but statistically significant increase in the FMR (0.10 and 0.07, respectively; P = 0.01). Sixty-two subjects completed 60 months of follow-up. FMR showed a significant increase even in the PI group at this time point (P < 0.03). Conclusions We observed a significant increase in the fat and lean body mass in all compartments and treatment groups over 36 and 60 months. Clinically irrelevant differences were found in fat distribution regardless of the treatment group and baseline characteristics. The data suggest that current antiretroviral regimens have little impact on BFD during the first years of treatment.

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Body Composition in Women after Radical Mastectomy

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17238991 ◽

2020 ◽

Vol 17 (23) ◽

pp. 8991

Author(s):

Jacek Wilczyński ◽

Piotr Sobolewski ◽

Rafał Zieliński ◽

Magdalena Kabała

Keyword(s):

Breast Cancer ◽

Physical Activity ◽

Body Composition ◽

Fat Mass ◽

Upper Limb ◽

Radical Mastectomy ◽

The Body ◽

Control Group ◽

Composition Analysis ◽

Prevention And Treatment

The aim of the study was to analyse the body composition among women after radical mastectomy. The body compositions of 30 women after radical mastectomy (study group) were compared with those of 30 healthy females (control group). The method of electrical bioimpedance was used to analyse body composition. The significant differences between the groups, unfavourable for women, following mastectomy concerned body mass (p = 0.021), BMI (p = 0.049), fat mass (%) (p = 0.007), fat mass (kg) (p = 0.005), total body water (%) (p = 0.002), left upper limb fat mass (p = 0.013) as well as right upper limb fat mass (p = 0.022). The body composition of women after radical mastectomy was significantly worse compared to the control group. The majority of subjects were overweight and had high levels of body fat. Abnormal body composition is a modifiable risk factor of breast cancer; therefore, improving lifestyle is important in the prevention and treatment of this disease. There is a need for education, dietary supervision and physical activity in women following radical mastectomy. The innovation of our study was the use of the modern bioelectrical impedance analysis (BIA) method, which does not cause ionisation and is a gold standard in the field of body composition analysis. In future research, we plan to broaden the assessment of lifestyle and the significance of diet and physical activity in the prevention and treatment of breast cancer.

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