Evolution of the myeloid-derived suppressor cells in advanced breast cancer and comparative analysis with a healthy population cohort.

2543 Background: High levels of myeloid-derived suppressor cells (MDSCs) seem a negative prognostic factor in advanced breast cancer (ABC) patients (pts). Preclinical studies suggest an immunomodulatory effect of some classical anti-tumor agents through alteration of MDSCs homeostasis. We analyzed the association of MDSCs and clinical evolution of ABC pts, taking into account the systemic treatment (tx) modulation of MDSCs levels in pts from two studies (“A”: GEICAM/2015-04 PANGEA-BREAST, NCT03025880 “Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC”, and “B”: PI-0502-2014 “Peripheral blood analyses of immune response induced by 1st line tx of ABC according to clinical guidelines”). Methods: MDSCs (CD33+ CD11b+) levels were determined by flow-cytometry in peripheral blood samples at three time points (basal, at cycles 3 and 6) from: 39 HER2-negative heavily pretreated pts from study “A”, 43 non-pretreated pts (all subtypes) from study “B” and 20 women from a healthy cohort (HC), with no cancer diagnosis. MDSCs levels from the different cohorts were compared and correlated with pts with Clinical Benefit (CB: partial/complete response + disease stabilization) vs pts with Progressive Disease (PD). Results: Tx response was assessed in 33 pts (85%) from study “A” and 39 pts (91%) from study “B”. CB was observed in 11 pts (28%) from study “A” and in 34 (79%) from study “B” while PD was observed in 22 pts (56%) from study “A” and in 5 (12%) from study “B”. Basal MDSCs levels were significantly higher in ABC pts (studies “A”+”B”) than in HC (15.95 vs 0.81 cells/µl, p = 0.009). At cycle 6, MDSCs were considerably lower in pts with CB vs DP (2.90 vs 13.75 cells/µl, p < 0.001). This decrease was more pronounced in study “B” than in study “A” pts (p < 0.001 vs p = 0.074, respectively), probably due to differences in number of events, tumor subtypes and tx between both studies. Conclusions: Our results suggest that ABC pts show alterations in MDSCs and that their decrease along tx may have a positive predictive value, highlighting the importance that immune-competent status may play in the evolution of ABC. MDSCs may represent a target for therapeutic purposes in ABC.

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Circulating Immune Biomarkers in Peripheral Blood Correlate With Clinical Outcomes in Advanced Breast Cancer

10.21203/rs.3.rs-228062/v1 ◽

2021 ◽

Author(s):

Natalia Palazón-Carrión ◽

Carlos Jiménez-Cortegana ◽

M. Luisa Sánchez-León ◽

Fernando Henao-Carrasco ◽

Esteban Nogales-Fernández ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Advanced Breast Cancer ◽

Peripheral Blood ◽

Clinical Benefit ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Immune Biomarkers

Abstract Identification of the different elements intervening at the immunoedition process, in each body compartment, seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40+ and PD-1+ T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer, were analyzed prior to and along the implementation of first line antineoplastic therapy. Subsequently, a formal comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients basally showed higher levels of myeloid derived suppressor cells (35.43, IR=180.73 vs 17.53, IR=16.96 cells/μl; p=0.001) and regulatory T cells (32.05, IR=29.84 vs 22.61, IR=13.57 cells/μl; p=0.001) in comparison with healthy women. Furthermore, after therapy, an increase in the number of activated T lymphocytes (expressing OX40), and a decrease of immune inhibitory cells (MDSCs, and Tregs), and the number of inhibited (or exhausted) T lymphocytes (expressing PD-1), could be ascertained in patients with clinical benefit (p≤0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be clearly correlated with clinical evolution, at least in ABC.

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Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

Scientific Reports ◽

10.1038/s41598-021-93838-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Natalia Palazón-Carrión ◽

Carlos Jiménez-Cortegana ◽

M. Luisa Sánchez-León ◽

Fernando Henao-Carrasco ◽

Esteban Nogales-Fernández ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Lymphocytes ◽

Regulatory T Cells ◽

Advanced Breast Cancer ◽

Peripheral Blood ◽

Clinical Benefit ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Immune Biomarkers

AbstractIdentification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40 + and PD-1 + T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer were analyzed along of first line antineoplastic therapy. Subsequently, a comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients showed higher basal levels of myeloid derived suppressor cells (35.43, IR = 180.73 vs 17.53, IR = 16.96 cells/μl; p = 0.001) and regulatory T cells (32.05, IR = 29.84 vs 22.61, IR = 13.57 cells/μl; p = 0.001) in comparison with healthy women. Furthermore, an increase in the number of activated T lymphocytes (expressing OX40), a decrease of immune inhibitory cells (MDSCs and Tregs) and inhibited T lymphocytes (expressing PD-1) were observed along the treatment in patients with clinical benefit (p ≤ 0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be correlated with clinical evolution, at least in ABC.

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Myeloid derived-suppressor cells in healthy women and in advanced breast cancer patients

Annals of Oncology ◽

10.1093/annonc/mdz095.058 ◽

2019 ◽

Vol 30 ◽

pp. iii19

Author(s):

N. Palazón Carrión ◽

M.L. Sánchez León ◽

C. Jiménez Cortegana ◽

F.J. Valdivia García ◽

I. Araujo Fernández ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Suppressor Cells ◽

Advanced Breast ◽

Myeloid Derived Suppressor Cells ◽

Breast Cancer Patients ◽

Healthy Women

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Study of pathological complete response rates with neoadjuvant concurrent chemoradiation with paclitaxel in locally advanced breast cancer

Annals of Oncology ◽

10.1093/annonc/mdz097.008 ◽

2019 ◽

Vol 30 ◽

pp. iii36

Author(s):

P. Iyer ◽

V. Radhakrishnan ◽

A. Balasubramanian ◽

V. Sridevi ◽

A. Krishnamurthy ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Pathological Complete Response ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Response Rates ◽

Complete Response ◽

Advanced Breast ◽

Concurrent Chemoradiation

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The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽

10.3390/cancers13040608 ◽

2021 ◽

Vol 13 (4) ◽

pp. 608

Author(s):

Toshiaki Iwase ◽

Aaroh Parikh ◽

Seyedeh S. Dibaj ◽

Yu Shen ◽

Tushaar Vishal Shrimanker ◽

...

Keyword(s):

Breast Cancer ◽

Body Composition ◽

Adipose Tissue ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

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Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

Cancers ◽

10.3390/cancers13215432 ◽

2021 ◽

Vol 13 (21) ◽

pp. 5432

Author(s):

Luis de la Cruz-Merino ◽

María Gion ◽

Josefina Cruz-Jurado ◽

Vanesa Quiroga ◽

Raquel Andrés ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Treatment Efficacy ◽

Triple Negative ◽

Objective Response ◽

Suppressor Cells ◽

Primary Objective ◽

Advanced Breast ◽

Breast Cancer Patients

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years; 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment >6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment >6 months.

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