Breast CancerNCT05468710
Inflammatory Blood Markers in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
An observational study of Breast Cancer, run by Ain Shams University.
Trial summary
Breast cancer is the most threatening disease in women. Neoadjuvant chemotherapy is a commonly used for the treatment. Inflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- Sep 2022to Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Invasive breast cancer, Above cT1 stage, all subtypes are included, who completed neoadjuvant systemic therapy.
Who may be able to join
- Patients aged 18 years old or more.
- Histologically proven invasive breast cancer.
- Above cT1 stage, any N Stage with no distant metastasis M0.
- All subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2.
- Patients who completed their systemic neoadjuvant therapy.
- Available baseline complete blood picture before starting treatment.
Who cannot join
- Second malignancy.
- Patients with early breast cancer cT1 (≤ 2 cm) N0.
- Metastatic patients M1.
- Patients with systemic inflammatory diseases or autoimmune diseases (Type I Diabetes mellitus, Systemic Lupus Erytheromatosis, Rheumatoid Arthritis, Sjogren's syndrome, Behcet disease).
- Pregnancy-related breast cancer.
- Patients with chronic diseases (liver cirrhosis, or end-stage renal disease).
Show all 10Show fewer
- Patients on systemic steroids as well as those under NSAIDS or other immunomodulators (as Methotraxate, Tacrolimus and Cyclosporine).
- Patient who received radiotherapy or endocrine or targeted therapy prior to neoadjuvant chemotherapy.
- Patients who started but didn't complete neoadjuvant systemic therapy.
- Patients who didn't undergo surgery after neoadjuvant systemic therapy.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Prognostic and Predictive Role of Inflammatory Blood Markers in Early and Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Breast cancer is the most threatening disease in women. Neoadjuvant chemotherapy is a commonly used for the treatment. Inflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. Inflammatory blood markers (IBM) reflect the balance between host inflammatory and immune status. Different IBM have been reported as prognostic factors for survival and predictive factors for pathological complete response and toxicity. Our aim to evaluate these IBM in breast cancer patients receiving neoadjuvant chemotherapy.
Read the detailed description
Inflammation, recognized as one of the 10 hallmarks of cancer (seventh hallmark of cancer), contributes to tumour proliferation, angiogenesis, metastasis, and resistance to chemotherapy. In general, white blood cell count reflects an individual's systemic and/or local inflammatory status. Neutrophils are known to regulate the tumour microenvironment and produce cytokines, chemokines, and growth factors that may promote angiogenesis as well as tumour cell proliferation and migration. The M2 phenotype tumour-associated macrophages (TAMs) deriving from circulating monocytes exist within the tumour microenvironment and promote metastasis and immunosuppression. It was reported that peripheral monocyte count was associated with the density of the TAMs, and high absolute monocyte count predicted poor survival in cancer patients. Platelets are other cells contributing to cancer-favoured inflammation by various mechanisms. For example, the activated platelets inhibit the interaction between tumour cells and cytolytic immune cells by forming a layer around tumour cells and support tumour growth via the secretion of several factors such as TGF-β. Hence, high platelet counts were reported to be associated with adverse outcomes in breast cancer. In contrast, lymphocytes are responsible for antitumor-specific immune response including T-lymphocyte tumour infiltration and cytotoxic T-lymphocyte-mediated antitumor activity.
Inflammatory blood markers (IBM) have emerged as potential prognostic factors for survival in different types of cancers including breast cancer, as well as predictive factors for histological response after neo-adjuvant chemotherapy. IBM include leucocyte count, lymphocyte count, neutrophil count, and ratios such as platelet to lymphocyte ratio (PLR) or neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR). Starting from these findings, NLR, MLR, and PLR, indices reflecting the balance between inflammation and immunoreaction in cancer, were reported to have predictive value in NAC response in many breast cancer studies.
There are conflicting reports about which index provides the best prediction for the efficacy of NAC in breast cancer. For example, Eren et al. reported that NLR was the only independent predictive factor of pathological complete response (pCR) among blood-derived inflammation markers in multivariate analysis. In another study conducted by Peng et al., multivariate analysis of 808 breast cancer patients showed that the lymphocyte-monocyte ratio was the only independent predictive factor for the efficacy of NAC among these inflammatory markers. In addition, Hu et al. stated that PLR had superior efficacy to NLR in predicting NAC response.
Different studies tried to integrate different peripheral blood immune cells as, Jiang et al., that used systemic immune-inflammation index (SII); is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, and stated that prognostic utility of (SII) was superior to that of NLR and PLR. Also Dong et al used the systemic inflammation response index (SIRI); an integrated indicator based on the counts of peripheral venous blood neutrophils(N), monocytes(M) and lymphocytes(L), and stated the prognostic value of the (SIRI) for pCR was superior to that of NLR.
Pan-Immune-Inflammation-Value (PIV) is a new blood-based biomarker integrating different peripheral blood immune cell subpopulations-neutrophil, platelet, monocyte, and lymphocyte. Due to its potential to represent comprehensively patient's immunity and systemic inflammation, PIV was proposed as a stronger predictor of outcomes in cancer patients receiving cytotoxic chemotherapy, immunotherapy, and targeted therapy. Recently, Ligorio reported that PIV was firmly associated with survival and outperformed NLR, PLR, and MLR in predicting survival in patients with HER-2 positive advanced breast cancer.
Sahin et al., stated that pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in Turkish women with breast cancer who received NAC.
Some studies stated that the SIRI and SII had no significance on toxicities like peripheral neuropathy and neutropenia. However, other studies reported NLR as predictive factor for febrile neutropenia.
These integrated indicators may fully reflect the balance between host inflammatory and immune status compared with NLR, MLR and PLR and other conventional haematological parameters.
These conflicting results have raised the need for a study to evaluate these inflammatory blood markers in patients with breast cancer receiving neo adjuvant chemotherapy.
- Conditions
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- The neutrophil to lymphocyte ratio (NLR) was provided by the ratio between the absolute count of neutrophils and the absolute count of lymphocytes (NLR = N /L)
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- The Platelet to lymphocyte ratio(PLR) was provided by the ratio between the absolute count of platelets and the absolute count of lymphocytes (PLR= P/L)
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Correlation between inflammatory blood marker (monocyte to lymphocyte ratio(MLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- The Monocyte to lymphocyte ratio (MLR) was provided by the ratio between the absolute count of monocytes and the absolute count of lymphocytes (MLR= M/L)
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Correlation between inflammatory blood marker (systemic immune-inflammation index(SII)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- The systemic immune-inflammation index is based on neutrophil (N), platelet (P) and lymphocyte (L) counts (SII = N × P/L) .
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- systemic inflammation response index (SIRI) is based on neutrophils(N), monocytes(M) and lymphocytes(L) (SIRI=N×M/L) .
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
- Pan-Immune-Inflammation-Value (PIV) is based on neutrophils(N), monocytes(M),platelet(P) and lymphocytes(L) (PIV=N×M×P/L).
- Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system).
- Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: 1 year
Secondary outcomes (6)
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and disease-free survival (DFS) and overall survival (OS).
- The neutrophil to lymphocyte ratio (NLR) was provided by the ratio between the absolute count of neutrophils and the absolute count of lymphocytes (NLR = N /L)
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and disease-free survival (DFS) and overall survival (OS).
- The Platelet to lymphocyte ratio(PLR) was provided by the ratio between the absolute count of platelets and the absolute count of lymphocytes (PLR= P/L)
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Correlation between inflammatory blood marker ( Monocyte to lymphocyte ratio (MLR)) and disease-free survival (DFS) and overall survival (OS).
- The Monocyte to lymphocyte ratio (MLR) was provided by the ratio between the absolute count of monocytes and the absolute count of lymphocytes (MLR= M/L)
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Correlation between inflammatory blood marker (Systemic immune-inflammation index (SII)) and disease-free survival (DFS) and overall survival (OS).
- The systemic immune-inflammation index (SII) is based on neutrophil (N), platelet (P) and lymphocyte (L) counts (SII = N × P/L) .
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and disease-free survival (DFS) and overall survival (OS).
- systemic inflammation response index (SIRI) is based on neutrophils(N), monocytes(M) and lymphocytes(L) (SIRI=N×M/L) .
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and disease-free survival (DFS) and overall survival (OS).
- Pan-Immune-Inflammation-Value (PIV) is based on neutrophils(N), monocytes(M),platelet(P) and lymphocytes(L) (PIV=N×M×P/L).
- Disease free survival (DFS) is defined as the time from diagnosis to the date of relapse (local recurrence or metastases to distant sites) and/or death from any cause.
- Overall survival (OS) is defined from the date of diagnosis to the date of death or the end of follow-up.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study startSep 2022 (estimated)
- Primary completionJul 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tawfik Helmy, Ain Shams University
- Investigators
- Nivine M Gado, phd, Study director, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05468710
- Sponsor's protocol ID
- MD 134/2022
- Status last verified
- Jul 2022
- First submitted
- 14 Jul 2022
- Last updated
- 21 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sahin AB, Cubukcu E, Ocak B, Deligonul A, Oyucu Orhan S, Tolunay S, Gokgoz MS, Cetintas S, Yarbas G, Senol K, Goktug MR, Yanasma ZB, Hasanzade U, Evrensel T. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021 Jul 19;11(1):14662. doi: 10.1038/s41598-021-94184-7.
PubMed 34282214Chen L, Kong X, Wang Z, Wang X, Fang Y, Wang J. Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy. J Cell Mol Med. 2020 Mar;24(5):2993-3021. doi: 10.1111/jcmm.14934. Epub 2020 Jan 27.
PubMed 31989747Corbeau I, Thezenas S, Maran-Gonzalez A, Colombo PE, Jacot W, Guiu S. Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers (Basel). 2020 Sep 18;12(9):2666. doi: 10.3390/cancers12092666.
PubMed 32962003Dong J, Sun Q, Pan Y, Lu N, Han X, Zhou Q. Pretreatment systemic inflammation response index is predictive of pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. BMC Cancer. 2021 Jun 14;21(1):700. doi: 10.1186/s12885-021-08458-4.
PubMed 34126950Eren T, Karacin C, Ucar G, Ergun Y, Yazici O, Imamoglu GI, Ozdemir N. Correlation between peripheral blood inflammatory indicators and pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer patients. Medicine (Baltimore). 2020 May 29;99(22):e20346. doi: 10.1097/MD.0000000000020346.
PubMed 32481414Hu Y, Wang S, Ding N, Li N, Huang J, Xiao Z. Platelet/Lymphocyte Ratio Is Superior to Neutrophil/Lymphocyte Ratio as a Predictor of Chemotherapy Response and Disease-free Survival in Luminal B-like (HER2-) Breast Cancer. Clin Breast Cancer. 2020 Aug;20(4):e403-e409. doi: 10.1016/j.clbc.2020.01.008. Epub 2020 Jan 30.
PubMed 32201163Jiang C, Lu Y, Zhang S, Huang Y. Systemic Immune-Inflammation Index Is Superior to Neutrophil to Lymphocyte Ratio in Prognostic Assessment of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy. Biomed Res Int. 2020 Dec 18;2020:7961568. doi: 10.1155/2020/7961568. eCollection 2020.
PubMed 33381583Ligorio F, Fuca G, Zattarin E, Lobefaro R, Zambelli L, Leporati R, Rea C, Mariani G, Bianchi GV, Capri G, de Braud F, Vernieri C. The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab. Cancers (Basel). 2021 Apr 19;13(8):1964. doi: 10.3390/cancers13081964.
PubMed 33921727Peng Y, Chen R, Qu F, Ye Y, Fu Y, Tang Z, Wang Y, Zong B, Yu H, Luo F, Liu S. Low pretreatment lymphocyte/monocyte ratio is associated with the better efficacy of neoadjuvant chemotherapy in breast cancer patients. Cancer Biol Ther. 2020;21(2):189-196. doi: 10.1080/15384047.2019.1680057. Epub 2019 Nov 4.
PubMed 31684807
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prognostic and Predictive Role of Inflammatory Blood Markers in Early and Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT05468710
- Acronym / sponsor ID
- MD 134/2022
- Conditions
- Breast Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- Sep 2022 (estimated)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 21 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Breast cancer is the most threatening disease in women. Neoadjuvant chemotherapy is a commonly used for the treatment. Inflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. Inflammatory blood markers (IBM) reflect the balance between host inflammatory and immune status. Different IBM have been reported as prognostic factors for survival and predictive factors for pathological complete response and toxicity. Our aim to evaluate these IBM in breast cancer patients receiving neoadjuvant chemotherapy.
Detailed description
Inflammation, recognized as one of the 10 hallmarks of cancer (seventh hallmark of cancer), contributes to tumour proliferation, angiogenesis, metastasis, and resistance to chemotherapy. In general, white blood cell count reflects an individual's systemic and/or local inflammatory status. Neutrophils are known to regulate the tumour microenvironment and produce cytokines, chemokines, and growth factors that may promote angiogenesis as well as tumour cell proliferation and migration. The M2 phenotype tumour-associated macrophages (TAMs) deriving from circulating monocytes exist within the tumour microenvironment and promote metastasis and immunosuppression. It was reported that peripheral monocyte count was associated with the density of the TAMs, and high absolute monocyte count predicted poor survival in cancer patients. Platelets are other cells contributing to cancer-favoured inflammation by various mechanisms. For example, the activated platelets inhibit the interaction between tumour cells and cytolytic immune cells by forming a layer around tumour cells and support tumour growth via the secretion of several factors such as TGF-β. Hence, high platelet counts were reported to be associated with adverse outcomes in breast cancer. In contrast, lymphocytes are responsible for antitumor-specific immune response including T-lymphocyte tumour infiltration and cytotoxic T-lymphocyte-mediated antitumor activity.
Inflammatory blood markers (IBM) have emerged as potential prognostic factors for survival in different types of cancers including breast cancer, as well as predictive factors for histological response after neo-adjuvant chemotherapy. IBM include leucocyte count, lymphocyte count, neutrophil count, and ratios such as platelet to lymphocyte ratio (PLR) or neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR). Starting from these findings, NLR, MLR, and PLR, indices reflecting the balance between inflammation and immunoreaction in cancer, were reported to have predictive value in NAC response in many breast cancer studies.
There are conflicting reports about which index provides the best prediction for the efficacy of NAC in breast cancer. For example, Eren et al. reported that NLR was the only independent predictive factor of pathological complete response (pCR) among blood-derived inflammation markers in multivariate analysis. In another study conducted by Peng et al., multivariate analysis of 808 breast cancer patients showed that the lymphocyte-monocyte ratio was the only independent predictive factor for the efficacy of NAC among these inflammatory markers. In addition, Hu et al. stated that PLR had superior efficacy to NLR in predicting NAC response.
Different studies tried to integrate different peripheral blood immune cells as, Jiang et al., that used systemic immune-inflammation index (SII); is based on neutrophil (N), platelet (P) and lymphocyte (L) counts, and stated that prognostic utility of (SII) was superior to that of NLR and PLR. Also Dong et al used the systemic inflammation response index (SIRI); an integrated indicator based on the counts of peripheral venous blood neutrophils(N), monocytes(M) and lymphocytes(L), and stated the prognostic value of the (SIRI) for pCR was superior to that of NLR.
Pan-Immune-Inflammation-Value (PIV) is a new blood-based biomarker integrating different peripheral blood immune cell subpopulations-neutrophil, platelet, monocyte, and lymphocyte. Due to its potential to represent comprehensively patient's immunity and systemic inflammation, PIV was proposed as a stronger predictor of outcomes in cancer patients receiving cytotoxic chemotherapy, immunotherapy, and targeted therapy. Recently, Ligorio reported that PIV was firmly associated with survival and outperformed NLR, PLR, and MLR in predicting survival in patients with HER-2 positive advanced breast cancer.
Sahin et al., stated that pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in Turkish women with breast cancer who received NAC.
Some studies stated that the SIRI and SII had no significance on toxicities like peripheral neuropathy and neutropenia. However, other studies reported NLR as predictive factor for febrile neutropenia.
These integrated indicators may fully reflect the balance between host inflammatory and immune status compared with NLR, MLR and PLR and other conventional haematological parameters.
These conflicting results have raised the need for a study to evaluate these inflammatory blood markers in patients with breast cancer receiving neo adjuvant chemotherapy.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Invasive breast cancer, Above cT1 stage, all subtypes are included, who completed neoadjuvant systemic therapy.
Key inclusion criteria (7 listed)
- Patients aged 18 years old or more.
- Histologically proven invasive breast cancer.
- Above cT1 stage, any N Stage with no distant metastasis M0.
- All subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2.
Key exclusion criteria (10 listed)
- Second malignancy.
- Patients with early breast cancer cT1 (≤ 2 cm) N0.
- Metastatic patients M1.
- Patients with systemic inflammatory diseases or autoimmune diseases (Type I Diabetes mellitus, Systemic Lupus Erytheromatosis, Rheumatoid Arthritis, Sjogren's syndrome, Behcet disease).
- Pregnancy-related breast cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* The neutrophil to lymphocyte ratio (NLR) was provided by the ratio between the absolute count of neutrophils and the absolute count of lymphocytes (NLR = N /L) * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* The Platelet to lymphocyte ratio(PLR) was provided by the ratio between the absolute count of platelets and the absolute count of lymphocytes (PLR= P/L) * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Correlation between inflammatory blood marker (monocyte to lymphocyte ratio(MLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* The Monocyte to lymphocyte ratio (MLR) was provided by the ratio between the absolute count of monocytes and the absolute count of lymphocytes (MLR= M/L) * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Correlation between inflammatory blood marker (systemic immune-inflammation index(SII)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* The systemic immune-inflammation index is based on neutrophil (N), platelet (P) and lymphocyte (L) counts (SII = N × P/L) . * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* systemic inflammation response index (SIRI) is based on neutrophils(N), monocytes(M) and lymphocytes(L) (SIRI=N×M/L) . * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade).
Time frame: 1 year
* Pan-Immune-Inflammation-Value (PIV) is based on neutrophils(N), monocytes(M),platelet(P) and lymphocytes(L) (PIV=N×M×P/L). * Pathological complete response (PCR) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (i.e., ypT0/Tis ypN0 in the current AJCC staging system). * Toxicity endpoint, will be retrieved and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
6 secondary outcomes
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Correlation between inflammatory blood marker (Platelet to lymphocyte ratio(PLR)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Correlation between inflammatory blood marker ( Monocyte to lymphocyte ratio (MLR)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Correlation between inflammatory blood marker (Systemic immune-inflammation index (SII)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Correlation between inflammatory blood marker (systemic inflammation response index (SIRI)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Correlation between inflammatory blood marker (Pan-Immune-Inflammation-Value (PIV)) and disease-free survival (DFS) and overall survival (OS).
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2022.
- Background: PubMed 34282214Sahin AB, Cubukcu E, Ocak B, Deligonul A, Oyucu Orhan S, Tolunay S, Gokgoz MS, Cetintas S, Yarbas G, Senol K, Goktug MR, Yanasma ZB, Hasanzade U, Evrensel T. Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy. Sci Rep. 2021 Jul 19;11(1):14662. doi: 10.1038/s41598-021-94184-7.
- Background: PubMed 31989747Chen L, Kong X, Wang Z, Wang X, Fang Y, Wang J. Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy. J Cell Mol Med. 2020 Mar;24(5):2993-3021. doi: 10.1111/jcmm.14934. Epub 2020 Jan 27.
- Background: PubMed 32962003Corbeau I, Thezenas S, Maran-Gonzalez A, Colombo PE, Jacot W, Guiu S. Inflammatory Blood Markers as Prognostic and Predictive Factors in Early Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. Cancers (Basel). 2020 Sep 18;12(9):2666. doi: 10.3390/cancers12092666.
- Background: PubMed 34126950Dong J, Sun Q, Pan Y, Lu N, Han X, Zhou Q. Pretreatment systemic inflammation response index is predictive of pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy. BMC Cancer. 2021 Jun 14;21(1):700. doi: 10.1186/s12885-021-08458-4.
- Background: PubMed 32481414Eren T, Karacin C, Ucar G, Ergun Y, Yazici O, Imamoglu GI, Ozdemir N. Correlation between peripheral blood inflammatory indicators and pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer patients. Medicine (Baltimore). 2020 May 29;99(22):e20346. doi: 10.1097/MD.0000000000020346.
- Background: PubMed 32201163Hu Y, Wang S, Ding N, Li N, Huang J, Xiao Z. Platelet/Lymphocyte Ratio Is Superior to Neutrophil/Lymphocyte Ratio as a Predictor of Chemotherapy Response and Disease-free Survival in Luminal B-like (HER2-) Breast Cancer. Clin Breast Cancer. 2020 Aug;20(4):e403-e409. doi: 10.1016/j.clbc.2020.01.008. Epub 2020 Jan 30.
- Background: PubMed 33381583Jiang C, Lu Y, Zhang S, Huang Y. Systemic Immune-Inflammation Index Is Superior to Neutrophil to Lymphocyte Ratio in Prognostic Assessment of Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy. Biomed Res Int. 2020 Dec 18;2020:7961568. doi: 10.1155/2020/7961568. eCollection 2020.
- Background: PubMed 33921727Ligorio F, Fuca G, Zattarin E, Lobefaro R, Zambelli L, Leporati R, Rea C, Mariani G, Bianchi GV, Capri G, de Braud F, Vernieri C. The Pan-Immune-Inflammation-Value Predicts the Survival of Patients with Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Breast Cancer Treated with First-Line Taxane-Trastuzumab-Pertuzumab. Cancers (Basel). 2021 Apr 19;13(8):1964. doi: 10.3390/cancers13081964.
- Background: PubMed 31684807Peng Y, Chen R, Qu F, Ye Y, Fu Y, Tang Z, Wang Y, Zong B, Yu H, Luo F, Liu S. Low pretreatment lymphocyte/monocyte ratio is associated with the better efficacy of neoadjuvant chemotherapy in breast cancer patients. Cancer Biol Ther. 2020;21(2):189-196. doi: 10.1080/15384047.2019.1680057. Epub 2019 Nov 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nivine M Gado, phd study director
Ain Shams University
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Ain Shams University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tawfik H Abdelmalak, MD (+201017031435, tawfikhelmy2009@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between inflammatory blood marker (neutrophil to lymphocyte ration (NLR)) and rate of pathological complete response (PCR), and neutropenia / peripheral neuropathy (CTCAE grade). (time frame: 1 year). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05468710, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2022.