Systematic Evaluation of HLA-G 3’Untranslated Region Variants in Locally Advanced, Non-Metastatic Breast Cancer Patients: UTR-1, 2 or UTR-4 are Predictors for Therapy and Disease Outcome

Despite major improvements in diagnostics and therapy in early as well as in locally advanced breast cancer (LABC), metastatic relapse occurs in about 20% of patients, often explained by early micro-metastatic spread into bone marrow by disseminated tumor cells (DTC). Although neoadjuvant chemotherapy (NACT) has been a successful tool to improve overall survival (OS), there is growing evidence that various environmental factors like the non-classical human leukocyte antigen-G (HLA-G) promotes cancer invasiveness and metastatic progression. HLA-G expression is associated with regulatory elements targeting certain single-nucleotide polymorphisms (SNP) in the HLA-G 3’ untranslated region (UTR), which arrange as haplotypes. Here, we systematically evaluated the impact of HLA-G 3’UTR polymorphisms on disease status, on the presence of DTC, on soluble HLA-G levels, and on therapy and disease outcome in non-metastatic LABC patients. Although haplotype frequencies were similar in patients (n = 142) and controls (n = 204), univariate analysis revealed that the UTR-7 haplotype was related to patients with low tumor burden, whereas UTR-4 was associated with tumor sizes >T1. Furthermore, UTR-4 was associated with the presence of DTC, but UTR-3 and UTR-7 were related to absence of DTC. Additionally, increased levels of soluble HLA-G molecules were found in patients carrying UTR-7. Regarding therapy and disease outcome, univariate and multivariate analysis highlighted UTR-1 or UTR-2 as a prognostic parameter indicative for a beneficial course of disease in terms of complete response towards NACT or progression-free survival (PFS). At variance, UTR-4 was an independent risk factor for a reduced OS besides already known parameters. Taken into account the most common HLA-G 3’UTR haplotypes (UTR-1–UTR-7, UTR-18), deduction of the UTR-1/2/4 haplotypes to specific SNPs revealed that the +3003C variant, unique for UTR-4, seemed to favor a detrimental disease outcome, while the +3187G and +3196G variants, unique for UTR-1 or UTR-2, were prognostic parameters for a beneficial course of disease. In conclusion, these data suggest that the HLA-G 3’UTR variants +3003C, +3187G, and +3196G are promising candidates for the prediction of therapy and disease outcome in LABC patients.

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Neoadjuvant radiotherapy in the approach of locally advanced breast cancer

ESMO Open ◽

10.1136/esmoopen-2019-000640 ◽

2020 ◽

Vol 5 (2) ◽

pp. e000640 ◽

Cited By ~ 1

Author(s):

Cláudia Sousa ◽

Mafalda Cruz ◽

Ana Neto ◽

Kayla Pereira ◽

Marta Peixoto ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Progression Free Survival ◽

Complete Response ◽

Intrinsic Subtype ◽

Advanced Breast ◽

Neoadjuvant Radiotherapy ◽

The Impact

BackgroundApproximately 4% of European patients are diagnosed with locally advanced breast cancer (LABC), a clinical condition commonly associated with poorer prognosis. Systemic therapy is the recommended initial treatment and when inoperability criteria prevails, radiotherapy (RT) should be used for tumour downstaging. This study intends to evaluate the impact of neoadjuvant radiotherapy (NART) in the treatment of inoperable LABC.MethodsA retrospective study of female patients, submitted to the NART between January 2014 and December 2018 at our institution. The evaluation of pathological response (pR) was made based on Pinder criteria. Primary endpoint: pR. Secondary endpoints: overall survival (OS) and progression-free survival (PFS). OS and PFS were calculated using the Kaplan-Meier method. Differences between groups were compared using Student’s t-test, ANOVA (Analysis of variance) and χ2 test. The statistical analyses were performed using Stata (V.13).ResultsA total of 76 patients were included, 18% with breast complete response. The 5 years OS was 54% and PFS was 61%. Subgroup analysis showed that pR >90% is correlated with a better OS (p=0.004). Basal-like intrinsic subtype is correlated with worse OS and PFS (p<0.05). No relation was found between response and age, intrinsic subtype, treatment performed and clinical T stage.ConclusionOur study confirms that NART is an effective downsizing treatment in inoperable LABC, allowing for a surgical resection regardless of the systemic treatment performed. Response to NART is independent of the intrinsic subtype and pR >90% is correlated with a better OS. Prospective studies to explore predictive response biomarkers are necessary in order to improve patient selection and optimisation of the treatment.

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Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽

10.3390/cancers12092657 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2657

Author(s):

Luca Campedel ◽

Paul Blanc-Durand ◽

Asker Bin Asker ◽

Jacqueline Lehmann-Che ◽

Caroline Cuvier ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative ◽

Univariate Analysis ◽

Tumor Infiltrating Lymphocytes ◽

Complete Response ◽

Prognostic Impact ◽

Breast Cancers ◽

Dose Dense ◽

The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

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Invited Commentary: The Impact of Neoadjuvant Chemotherapy on Patients with Locally Advanced Breast Cancer in a Nigerian Semiurban Teaching Hospital: A Single-Center Descriptive Study

World Journal of Surgery ◽

10.1007/s00268-010-0578-1 ◽

2010 ◽

Vol 34 (8) ◽

pp. 1779-1781

Author(s):

Ines Buccimazza

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Teaching Hospital ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Descriptive Study ◽

Advanced Breast ◽

Single Center ◽

The Impact

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The influence of seminal events on the transition from adjuvant to neoadjuvant chemoradiation in the treatment of locally advanced rectal adenocarcinoma (LARC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.631 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 631-631

Author(s):

Jeremy Warner ◽

Rebecca A. Miksad ◽

Deborah Nagle ◽

Robert Najarian ◽

Michael Goldstein

Keyword(s):

Meta Analysis ◽

Univariate Analysis ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Neoadjuvant Chemoradiation ◽

Phase Iii ◽

Definitive Treatment ◽

Current Standard ◽

Pivotal Phase ◽

The Impact

631 Background: Factors leading to uptake of new oncology treatment innovations are poorly understood. In particular, the degree to which seminal events, such as report of pivotal phase III trials, influence practice is unclear. For example, preoperative (pre-op) 5-fluorouracil + radiation (5-FU + RT) is the current standard of care for definitive treatment of LARC. However, postoperative (post-op) 5-FU + RT was standard before the seminal German Rectal Cancer Study Group (GRCSG) results were published. We investigated the impact of seminal events on the change in practice pattern from pre- to post-op 5-FU + RT at our institution. Methods: Patients with LARC (T2N+; any T3; any T4) treated at our institution between 1994-2010 were identified from the cancer registry. The date of diagnosis was compared to the dates of three seminal events: A) JAMA meta-analysis publication; B) publication of GRCSG results; C) founding of a multidisciplinary clinic at our institution. Pearson Chi square was used for univariate analysis. Results: 334 patients were evaluable. RT +/- 5-FU was delivered pre-op for 207 patients, post-op for 127 patients. The unadjusted odds ratio (OR) for receiving pre-op treatment after vs. before each seminal event was similar: (A) 4.16; (B) 4.08; (C) 3.91. When patients diagnosed prior to (A) or after (C) were excluded, (B) appeared to have a smaller effect, OR 2.07 (p = .053) (Table). Conclusions: All seminal events had similar associated OR, indicating that the process of uptake of the innovation of pre-op 5-FU + RT was gradual. The seminal GRCSG publication, when temporally isolated, had only modest effect. This suggests that report of seminal results is necessary but not sufficient for uptake of a new therapy innovation in LARC at our institution. Whether this pattern of uptake is generalizable is worthy of further investigation. [Table: see text]

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Prognostic significance of estrogen, progesterone and HER2 receptors’ status conversion following neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from a tertiary Cancer Center in Saudi Arabia

PLoS ONE ◽

10.1371/journal.pone.0247802 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247802

Author(s):

Khalid Al-Saleh ◽

Tareq Salah ◽

Maria Arafah ◽

Sufia Husain ◽

Ammar Al-Rikabi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Univariate Analysis ◽

Locally Advanced ◽

Receptor Expression ◽

Advanced Breast ◽

Her2 Positive ◽

Receptor Conversion

Background The prognostic impact of neoadjuvant chemotherapy (NAC) on the receptor expression status in patients with locally advanced breast cancer (LABC) is still not fully understood. We aimed to evaluate the changes in hormone (estrogen and progesterone) receptor (HR) and human epidermal growth factor receptor 2 (HER2) status post-NAC and their correlation with survival. Methods Patients with LABC who have received NAC between 2008 and 2015 and have been followed up till December 2019 at the Oncology Center, King Saud University, KSA were analyzed retrospectively. biomarker analysis of ER, PR & HER2 were done using immunohistochemistry (IHC) and Fluorescent in situ hybridization. Results Ninety-one patients fulfilled the inclusion criteria. HR status changed in 21(23.1%) patients, with a significant difference between patients with stable receptors and those with any receptor conversion; p = 0.000. Five (5.5%) initially HER2 negative tumors became HER2 positive and 10 (11%) initially HER2 positive tumors became HER2 negative after NAC. The difference in HER2 expression level before and after NAC was not statistically significant (p = 0.302). Univariate analysis relating patients’ characteristics and 10-years disease-free survival (DFS) showed only significant correlations with the expressions of ER, PR, and any receptor conversion, (ER and/or PR) p< 0.001, p< 0.001, and p = 0.001; respectively. In the univariate analysis, none of the clinicopathological features showed a significant correlation with the OS except for the molecular subtypes P<0.001. Conclusions Patients with LABC have significant changes in the ER and PR receptor status following NAC. Post-NAC expressions change of ER and PR (ER and/or PR) are correlated to DFS. Retesting of the hormone receptors should be considered after NAC in Saudi patients with LABC.

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Neoadjuvan Chemotheraphy Responses to Local Advanced Breast Cancer Patients at Dr Moh Hoesin Hospital Palembang

SRIWIJAYA JOURNAL OF MEDICINE ◽

10.32539/sjm.v3i3.131 ◽

2020 ◽

Vol 3 (3) ◽

pp. 51-58

Author(s):

Aldo Giovanno ◽

Mgs. Irsan Saleh ◽

Nur Qodir ◽

Mulawan Umar

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Cancer Patients ◽

Univariate Analysis ◽

Locally Advanced ◽

Radical Mastectomy ◽

Advanced Breast ◽

Chemotherapy Response ◽

Breast Cancer Patients

Breast cancer is a malignancy which invaded breast tissue in the form of ductal or lobular. One most therapywhich is given is neoadjuvant chemotherapy. Neoadjuvant Chemotherapy can reduce tumor size so that surgerycan be performed with good breast removal with Modification of Radical Mastectomy (MRM) and BreastConservative Therapy (BCT). This purpose from this research is to find out neoadjuvant chemotherapy response inLocally Advanced Breast Cancer Patients which has received chemotherapy treatment in RSUP dr MohammadHoesin Palembang. This observational descriptive study was conducted at RSUP Mohammad Hoesin Palembang inthe period between October until November 2019. The sample of this study was locally advanced breast Cancerpatients who underwent chemotherapy that met the inclusion and exclusion criteria. The data were obtained byinterviews and observed medical records from the patients which were then analyzed by univariate analysis usingSPSS version 25. In this study there were 34 locally advanced breast cancer patients who fulfilled the inclusion andexclusion criteria. 24 of 34 patients (70,6%) received positive response and 10 of 34 patients (29,4%) receivednegative response.

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The impact of socioeconomic factors on outcomes of patients with locally advanced rectal cancer (LARC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.612 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 612-612

Author(s):

Joanna Gotfrit ◽

Tharshika Thangarasa ◽

Horia Marginean ◽

Shaan Dudani ◽

Rachel Anne Goodwin ◽

...

Keyword(s):

Rectal Cancer ◽

Census Data ◽

Performance Status ◽

Univariate Analysis ◽

Locally Advanced ◽

Disease Free Survival ◽

Cancer Center ◽

Cancer Centre ◽

Driving Time ◽

The Impact

612 Background: Patients with rectal cancer may experience disparities in outcomes due to various socioeconomic (SES) factors. We assessed the impact of SES factors on outcomes in patients with LARC who received neoadjuvant chemoradiation (nCRT) and surgery (Sx) in three Canadian provinces. Methods: Associations between clinical variables, demographics, community characteristics (2015 Canadian Census data), distance and time to the nearest cancer center (mapping software), and outcomes were evaluated. Results: 1,098 patients were included (Table 1). Median follow-up time was 67.8 months. The 5-year survival rate was 0.80 (95% CI 0.77-0.82). Factors predictive of disease-free survival in univariate analysis (UVA) included age, worse performance status (PS), driving time > 1 hour, median community income, and driving distance > 100 km. Factors that remained significant in multivariate analysis (MVA) included age (HR 1.01; 95% CI 1.00-1.02; p = 0.01), worse PS (HR 1.30; 95% CI 1.01-1.68; p = 0.04) and driving time > 1 hour (HR 1.31; 95% CI 1.01-1.71; p = 0.04). Factors predictive of overall survival in UVA included age, worse PS, driving time to the cancer centre > 1 hour, median community income, and community proportion with post-secondary education. Factors that remained significant in MVA included age (HR 1.03; 95% CI 1.02-1.04; p < 0.001), worse PS (HR 1.41; 95% CI 1.03-1.94; p = 0.03), and median community income (HR 1.00; 95% CI 1.00-1.00; p = 0.05). Conclusions: Outcomes of patients with LARC undergoing nCRT are significantly associated with driving time to the nearest cancer centre and community household income. Further efforts to understand and reduce these socioeconomic disparities are warranted. [Table: see text]

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