24P TGF-βRI contributes to tamoxifen response in luminal B breast cancer with HER2-negative phenotype

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

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AGE FEATURES OF MOLECULAR-BIOLOGICAL SUBTYPES OF BREAST CANCER

Journal of Ural Medical Academic Science ◽

10.22138/2500-0918-2020-17-2-187-192 ◽

2020 ◽

Vol 17 (2) ◽

pp. 187-192

Author(s):

E.A. Novikova ◽

◽

O.V. Kostromina ◽

D.V. Mikhailov ◽

S.L. Leontiev ◽

...

Keyword(s):

Breast Cancer ◽

Hormone Receptors ◽

Age Groups ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Age Related ◽

Age Features ◽

Immunohistochemical Studies ◽

Triple Negative Subtype

Aim. The aim of the study was to determine the presence of peculiarities of the age structure in patients with various surrogate molecular biological subtypes of breast cancer. Materials and research methods. This work analyzes the age-related characteristics of the occurrence of molecular biological subtypes in 499 patients with invasive breast cancer. All cases were divided into 5 molecular biological subtypes based on immunohistochemical studies of hormone receptors, Her2, Ki-67. The average age of the patients was 53.4±0.39 years, the predominant group was patients from 50 to 60 years (37.2% of the total). Research results. In patients under 40 years old, the triple negative subtype prevailed (44.8%). Luminal A subtype prevailed in the groups 51-60 years old (more than 41.4%) and over 60 years old (39.7%). Luminal B (Her2-) subtype was equally found in all age groups.

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Recent Discoveries of Macromolecule- and Cell-Based Biomarkers and Therapeutic Implications in Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22020636 ◽

2021 ◽

Vol 22 (2) ◽

pp. 636

Author(s):

Hsing-Ju Wu ◽

Pei-Yi Chu

Keyword(s):

Breast Cancer ◽

Normal Breast ◽

New Drugs ◽

Cancer Type ◽

Luminal A ◽

Luminal B ◽

Therapeutic Implications ◽

Whole Cells ◽

Diagnosis And Prognosis ◽

Novel Biomarkers

Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER−, PR−, and HER2−), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed. In this review, we summarize and focus on the recent discoveries of promising macromolecules and cell-based biomarkers for the diagnosis and prognosis of breast cancer and provide implications for therapeutic strategies.

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Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

Tumori Journal ◽

10.1177/03008916211012341 ◽

2021 ◽

Vol 107 (1_suppl) ◽

pp. 12-12

Author(s):

D Aissaoui ◽

M Bohli ◽

R Ben Amor ◽

J Yahyaoui ◽

A Hamdoun ◽

...

Keyword(s):

Breast Cancer ◽

Treatment Response ◽

Inflammatory Breast Cancer ◽

Hormone Receptor ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

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Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Cells ◽

10.3390/cells10071685 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1685

Author(s):

Antonino Grassadonia ◽

Vincenzo Graziano ◽

Laura Iezzi ◽

Patrizia Vici ◽

Maddalena Barba ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Post Treatment ◽

Neutrophil To Lymphocyte Ratio ◽

Luminal Breast Cancer ◽

Luminal A ◽

Luminal B ◽

Lymphocyte Ratio ◽

Cell Counts ◽

Pre Treatment

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

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