Negative Breast Cancer Patients Research Articles

The Rochester Modified Magee Algorithm (RoMMa): An Outcomes Based Strategy for Clinical Risk-Assessment and Risk-Stratification in ER Positive, HER2 Negative Breast Cancer Patients Being Considered for Oncotype DX® Testing.

Multigene genomic profiling has become the standard of care in the clinical risk-assessment and risk-stratification of ER+, HER2- breast cancer (BC) patients, with Oncotype DX® (ODX) emerging as the genomic profile test with the most support from the international community. The current state of the health care economy demands that cost-efficiency and access to testing must be considered when evaluating the clinical utility of multigene profile tests such as ODX. Several studies have suggested that certain lower risk patients can be identified more cost-efficiently than simply reflexing all ER+, HER2- BC patients to ODX testing. The Magee equationsTM use standard histopathologic data in a set of multivariable models to estimate the ODX recurrence score. Our group published the first outcome data in 2019 on the Magee equationsTM, using a modification of the Magee equationsTM combined with an algorithmic approach-the Rochester Modified Magee algorithm (RoMMa). There has since been limited published outcome data on the Magee equationsTM. We present additional outcome data, with considerations of the TAILORx risk-stratification recommendations. 355 patients with an ODX recurrence score, and at least five years of follow-up or a BC recurrence were included in the study. All patients received either Tamoxifen or an aromatase inhibitor. None of the patients received adjuvant systemic chemotherapy. There was no significant difference in the risk of recurrence in similar risk categories (very low risk, low risk, and high risk) between the average Modified Magee score and ODX recurrence score with the chi-square test of independence (p > 0.05) or log-rank test (p > 0.05). Using the RoMMa, we estimate that at least 17% of individuals can safely avoid ODX testing. Our study further reinforces that BC patients can be confidently stratified into lower and higher-risk recurrence groups using the Magee equationsTM. The RoMMa can be helpful in the initial clinical risk-assessment and risk-stratification of BC patients, providing increased opportunities for cost savings in the health care system, and for clinical risk-assessment and risk-stratification in less-developed geographies where multigene testing might not be available.

Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China

BackgroundReal-world data of Palbociclib are insufficient in China. This study aimed to investigate the treatment pattern and real-world outcomes in hormone receptor positive and human epidermal growth factor 2 receptor negative (HR+/HER2-) metastatic breast cancer (MBC) patients treated with Palbociclib in the northwest of China.MethodsHR+/HER2- MBC patients who received Palbociclib in 8 centers from July 2017 to September 2019 were retrospectively included in this study. Real-world objective response rate (ORR), progression-free survival (PFS) and safety profiles were analyzed. The survival curves were plotted by the Kaplan-Meier method to analyze PFS, which was verified by the log-rank test.ResultsIn total, 211 women were eligible for the analysis. A total of 85 patients (40.3%), 78 (37.0%), and 48 (22.7%) received Palbociclib in the first-, second-, third- or later-line setting, respectively. 46 patients achieved partial response and 145 patients experienced stable disease, with an ORR of 21.8% and a disease control rate of 90.5%. Following a median follow-up period of 14.2 months, the median PFS was 12.2 months (95% confidence interval, 10.1-14.3 m), and the median overall survival was not reached. Early Palbociclib initiation, sensitivity or acquired resistance to endocrine therapy, estrogen receptor and progesterone receptor double positivity, less than 3 metastatic sites, without visceral metastasis, bone metastasis only, without prior chemotherapy or endocrine therapy were associated with a prolonged PFS in MBC (All P < 0.05). The most common grade 3 or 4 adverse events (AE) was neutropenia (36.5%), and the most common nonhematologic AE was fatigue (10.9%). No patient experienced AE leading to treatment discontinuation.ConclusionPalbociclib plus endocrine therapy exhibited favorable effectiveness and manageable toxicities in the real-world setting, supporting their use in Chinese patients with HR+/HER2 − MBC.

GRHL2-controlled gene expression networks in luminal breast cancer

Grainyhead like 2 (GRHL2) is an essential transcription factor for development and function of epithelial tissues. It has dual roles in cancer by supporting tumor growth while suppressing epithelial to mesenchymal transitions (EMT). GRHL2 cooperates with androgen and estrogen receptors (ER) to regulate gene expression. We explore genome wide GRHL2 binding sites conserved in three ER⍺/GRHL2 positive luminal breast cancer cell lines by ChIP-Seq. Interaction with the ER⍺/FOXA1/GATA3 complex is observed, however, only for a minor fraction of conserved GRHL2 peaks. We determine genome wide transcriptional dynamics in response to loss of GRHL2 by nascent RNA Bru-seq using an MCF7 conditional knockout model. Integration of ChIP- and Bru-seq pinpoints candidate direct GRHL2 target genes in luminal breast cancer. Multiple connections between GRHL2 and proliferation are uncovered, including transcriptional activation of ETS and E2F transcription factors. Among EMT-related genes, direct regulation of CLDN4 is corroborated but several targets identified in other cells (including CDH1 and ZEB1) are ruled out by both ChIP- and Bru-seq as being directly controlled by GRHL2 in luminal breast cancer cells. Gene clusters correlating positively (including known GRHL2 targets such as ErbB3, CLDN4/7) or negatively (including TGFB1 and TGFBR2) with GRHL2 in the MCF7 knockout model, display similar correlation with GRHL2 in ER positive as well as ER negative breast cancer patients. Altogether, this study uncovers gene sets regulated directly or indirectly by GRHL2 in luminal breast cancer, identifies novel GRHL2-regulated genes, and points to distinct GRHL2 regulation of EMT in luminal breast cancer cells.6_BaCm7NaLGTK4K5qg2XWLVideo

Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors provide promising results for treating hormone receptor-positive breast cancer. However, the efficacy of CDK4/6 inhibitors remains uncertain in triple negative breast cancer (TNBC) patients with particularly carrying RB-deficient tumors. Poly-(ADP-ribose) polymerase (PARP) inhibitors offer a therapeutic strategy for the treatment of BRCA-mutated TNBC patients. However, the acquired drug resistance, changes in the cell cycle regulation, and DNA damage repair have demonstrated the necessity for developing new combination strategies. This preclinical study assessed a combinatory treatment of the CDK4/6 inhibitor abemaciclib with PARP inhibitors talazoparib (TAL) in HCC1937 BRCA-mutated RB-deficient TNBC cells and TAL-resistant HCC1937-R cells through WST-1 analysis, annexin V, cell cycle, acridine orange/propidium iodide staining, RT-PCR, and apoptosis array. Our findings revealed that abemaciclib and TAL combination synergistically suppressed the growth of TNBC cells and overcame TAL resistance through G0/G1 arrest and the activity of both intrinsic and extrinsic apoptotic pathways. These preliminary results suggest that the combination of abemaciclib and TAL could expand the use of these inhibitors in BRCA mutated and RB deficient TNBC patients and potentially overcomes PARP inhibitors resistance.

Influencing Factors of Bone Metastasis in Human Epidermal Growth Factor Receptor 2 Negative Breast Cancer and Efficacy of Capecitabine Plus Docetaxel

The clinical data characteristics of human epidermal growth factor receptor 2 negative breast cancer patients were analyzed to investigate the influencing factors of bone metastasis. A total of 754 patients with human epidermal growth factor receptor 2 negative breast cancer admitted to the First People's Hospital of Lianyungang from January 2017 to September 2022, including 273 patients in the bone metastasis group and 481 patients in the non-bone metastasis group, were retrospectively and systematically evaluated for their clinic pathological characteristics, treatment modalities and their influencing factors. Chi-square test and Mann-Whitney U test were used to calculate the differences in clinical data between patients with human epidermal growth factor receptor 2 negative bone metastases and those without bone metastases. Binary logistic regression was performed to analyses the risk factors for the development of bone metastases in human epidermal growth factor receptor 2 negative breast cancer. A significant difference was found between the patients in the bone metastasis group and the non-bone metastasis group in terms of T-stage, N-stage, estrogen receptor, progesterone receptor, tumour molecular classification, axillary lymph node metastasis and quality of life scores (functional assessment of cancer therapy-breast) after combined therapy with capecitabine plus docetaxel (Z=-2.706, Z=-2.864, χ2=75.954, χ2=55.618, χ2=114.854, χ2=305.211, χ2=66.945 and p<0.05), while statistical significance was absent in terms of age and location of the primary site (χ2=2.888, χ2=1.903 and p>0.05). Logistic regression analysis revealed that high T-stage, luminal A molecular staging and the occurrence of axillary lymph node metastases were all risk factors for bone metastases in human epidermal growth factor receptor 2 negative breast cancer patients (OR=4.352, 95 % CI=2.147 to 8.823, p<0.001; OR=0.281, 95 % CI=0.179 to 0.441, p<0.001 and OR=12.766, 95 % CI=6.712 to 24.283, p<0.001). The occurrence of bone metastases in human epidermal growth factor receptor 2 negative breast cancers was statistically correlated with T-stage, N-stage, estrogen receptor, progesterone receptor, molecular tumour staging, axillary lymph node metastasis and patient quality of life scores after combined therapy with capecitabine plus docetaxel. High T-stage, luminal A and axillary lymph node metastasis were all risk factors. Combined therapy of capecitabine and docetaxel provides significant efficacy in patients with human epidermal growth factor receptor 2 negative breast cancer bone metastases.

Adjuvant denosumab in early breast cancer: a systematic review and meta-analysis of randomized controlled clinical trials.

In early breast cancer (BC) the impact of denosumab on survival outcomes is still unclear. We undertook a systematic review and meta-analysis to assess efficacy and safety of adjuvant denosumab in addition to standard anticancer therapy. PubMed, CENTRAL, Scopus, Embase, and oncological meetings websites were screened to identify potentially eligible randomized controlled trials (RCTs). Survival outcomes were disease-free survival (DFS), bone-metastasis-free survival (BMFS), and overall survival (OS). Fracture incidence and time to first fracture were bone-health outcomes. Osteonecrosis of the jaw (ONJ), atypical femur fractures (AFF), and other adverse events were also evaluated. Pooled hazard ratios (HRs) and risk ratios (RR) with respective 95% confidence interval (95% CI) were computed using a random-effects model. Exploratory subgroup analyses were performed. Two phase III RCTs were included, the Austrian Breast & Colorectal Cancer Study Group-18 (ABCSG-18) and the D-CARE trials, for a total of 7929 patients. In the ABCSG-18 trial, denosumab was administered every 6 months during endocrine therapy (for a median of seven cycles) while the D-CARE trial used an intensive schedule for a total treatment duration of 5 years. Adjuvant denosumab showed no difference in DFS (HR: 0.932; 95% CI: 0.748-1.162), BMFS (HR: 0.9896; 95% CI: 0.751-1.070), and OS (HR: 0.917; 95% CI: 0.718-1.171) compared to placebo in the overall population. In hormone receptor positive/human epidermal growth factor receptor 2 (HER2) negative BC patients, a DFS (HR: 0.883; 95% CI: 0.782-0.996) and BMFS (HR: 0.832; 95% CI: 0.714-0.970) benefit was observed and BMFS was prolonged in all hormone receptor positive patients (HR: 0.850; 95% CI: 0.735-0.983). Fracture incidence (RR: 0.787; 95% CI: 0.696-0.890) and time to first fracture (HR: 0.760; 95% CI: 0.665-0.869) were also improved. No increase in overall toxicity was seen with denosumab and no differences were observed for ONJ and AFF between the 60-mg every 6-month schedule and placebo. Denosumab addition to anticancer treatment does not improve DFS, BMFS, or OS in the overall population, although a DFS improvement was observed in hormone receptor positive/HER2 negative BC patients and a BMFS improvement in all hormone receptor positive patients. Bone-health outcomes were improved with no added toxicity with the 60-mg schedule. PROSPERO identifier: CRD42022332787.

Synergism of FAK and ROS1 inhibitors in the treatment of CDH1-deficient cancers mediated by FAK-YAP signaling.

CDH1 deficiency is common in diffuse gastric cancer and triple negative breast cancer patients, both of which still lack effective therapeutics. ROS1 inhibition results in synthetic lethality in CDH1-deficient cancers, but often leads to adaptive resistance. Here, we demonstrate that upregulation of the FAK activity accompanies the emergence of resistance to ROS1 inhibitor therapy in gastric and breast CDH1-deficient cancers. FAK inhibition, either by FAK inhibitors or by knocking down its expression, resulted in higher cytotoxicity potency of the ROS1 inhibitor in CDH1-deficient cancer cell lines. Co-treatment of mice with the FAK inhibitor and ROS1 inhibitors also showed synergistic effects against CDH1-deficient cancers. Mechanistically, ROS1 inhibitors induce the FAK-YAP-TRX signaling, decreasing oxidative stress-related DNA damage and consequently reducing their anti-cancer effects. The FAK inhibitor suppresses the aberrant FAK-YAP-TRX signaling, reinforcing ROS1 inhibitor's cytotoxicity towards cancer cells. These findings support the use of FAK and ROS1 inhibitors as a combination therapeutic strategy in CDH1-deficient triple negative breast cancer and diffuse gastric cancer patients.

Abstract PR007: Tumoral infiltrating lymphocytes as a prognostic factor in triple negative breast cancer patients from Colombia

Abstract Introduction: Triple negative breast cancer (TNBC), occurs in 10%-20% of all breast cancer and presents a higher frequency in Latinas compared to non-Hispanic white women. It is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better overall survival and higher probability to achieve pathological complete response (pCR). Objective: This is the first study in Colombian women aimed to explore stromal TILs (sTILs) level and composition as a prognostic and predictive biomarker in TNBC. Methods: A total of 195 TNBC tumor biospecimens from patients diagnosed between 2008-2016 in 3 Colombian health institutions were included. Stromal TILs (sTILs) was evaluated following the recommendations of the International TILs Working Group 2014 in hematoxylin &amp; eosin slides from pre-treatment samples. The number of positive cells for CD4 and CD8 was evaluated by immunohistochemistry and digital image capture. Parametric and non-parametric tests were used to evaluate differences in clinic-pathological characteristics according to sTILs levels and composition. Differences in overall survival were analyzed using Kaplan-Meier curves and the log-rank test. Cox regression analysis was used to analyze sTILs as a prognostic marker for overall survival. A logistic regression model was applied to evaluate the association of sTILs with pCR. Results: Tumors with high sTILs levels were more likely to be early stage (64.4% stage I/II) compared to tumors with low sTILs levels (35.5%). Additionally, when compared patients with high sTILs vs. low sTILs, a higher percentage of patients with high sTILs didn’t receive neoadjuvant chemotherapy (NAC) (high:50% vs. low:32.7%, p=0.025) and received more conservative surgeries (high:60% vs. low:37.9%, p&amp;lt;0.05). Similar results were observed for patients with high CD4/8 infiltration. Longer overall survival times were observed in patients with high sTILs (84.9 mo vs. 41.4 mo, p&amp;lt;0.05), as well as in patients with high CD4+ infiltration (p&amp;lt;0.05) and CD8+ (p&amp;lt;0.015). In the multivariate analysis, low levels of sTILs was found to be independent prognostic factor associated with a higher risk of death (HR: 1.59, 95% CI 1.01-2.48). Regarding sTILs as a predictive biomarker, a higher number of patients with high sTILs and high CD4+ cells achieved clinical complete response to NAC (sTILs: 28.6% vs. 9.3%, p=0.022; CD4: 29% vs 9.4%, p=0.032) and pCR (sTILs: 42.9% vs. 15.8%, p=0.023; for CD4: 43.3% vs 16.3%, p=0.006) compared to patients with low infiltration. Likewise, a statistically significant association between sTILs and pCR was observed (OR: High sTILs 1.486, 95% CI 1.14 - 2.013). Similar results were observed for high CD4 and CD8 infiltration (OR: 1.262, 95% CI 1.061 - 1.536, OR: 1.337, 1.085 - 1.694, respectively). Conclusions: Our results suggest that sTILs levels are a prognostic marker for overall survival and a predictive marker for pCR in TNBC patients from Colombia as has been reported in previous studies including biospecimens from mostly European ancestry patients. Citation Format: Carlos A. Huertas-Caro, Mayra A. Ramirez, Diego Felipe Ballen, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez. Tumoral infiltrating lymphocytes as a prognostic factor in triple negative breast cancer patients from Colombia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR007.

A retrospective cohort study comparing reconstructive techniques and outcomes in post-mastectomy triple negative breast cancer patients.

Up to 42% of all breast cancer patients undergo post-mastectomy reconstruction, however reconstructive techniques have not been widely studied in patients with triple negative breast cancer (TNBC). Reconstructive complications may delay adjuvant treatments; in TNBC, which inherently carries an increased risk of locoregional recurrence, this can greatly affect oncological outcomes. Therefore, we evaluate factors influencing choice of reconstructive techniques following mastectomy in TNBC patients and assess operative and oncologic safety outcomes. A single institution retrospective chart review identified TNBC patients who underwent post-mastectomy reconstruction between 2010 to 2020. Clinical characteristics collected included demographics, cancer history, reconstructive techniques [autologous-based reconstruction (ABR) vs. implant-based reconstruction (IBR)] and surgical and oncologic outcomes such as complications, recurrence, and mortality. Factors impacting whether patients underwent ABR versus IBR were assessed, as well as differences in outcomes between the two procedures. Statistical significance was defined as P<0.05. During the 10-year period, 52.9% (n=127) of all post-mastectomy TNBC patients (n=240) underwent breast reconstruction, most frequently immediately after mastectomy (97.0%). Most patients underwent IBR compared to ABR (82.4% vs. 14.5%). Patients undergoing ABR were older than IBR patients (54.3 vs. 46.4 years; P=0.040) and had a higher body mass index (BMI; 30.0 vs. 26.1 kg/m2; P=0.007). Patients more often pursued ABR if they had a prior breast cancer history (36.8% vs. 16.7%; P=0.041) or experienced TNBC recurrence (26.3% vs. 9.3%; P=0.034), while primary TNBC patients more often opted for IBR. Reconstructive type did not impact complications (ABR 31.6% vs. IBR 16.8%, P=0.131), recurrence (ABR 15.8% vs. IBR 13.0%, P=0.719), or mortality (ABR 0.0% vs. IBR 6.5%, P=0.593) rates. Factors such as age, BMI, and breast cancer history impacted choice of reconstructive technique among TNBC women. No differences in complications, recurrence, or mortality occur in these high-risk patients regardless of reconstructive technique, highlighting that neither ABR nor IBR is superior in regard to surgical and oncologic safety in post-mastectomy TNBC patients.

Factors Affecting Local and Regional Recurrence-Free Survival in Triple Negative Breast Cancer Patients: A Single Center Experience

Üçlü negatif meme kanserinde (ÜNMK) hastalık erken evrede tespit edilse de, hastalıksız sağkalım (HSK) ve sağkalım, ÜNMK olmayanlara göre daha düşüktür ve lokal nüks/ uzak metastaz daha erken ortaya çıkma eğilimindedir. Lokal ileri ÜNMK hastalarında neoadjuvan tedavi (NKT) öncelikle tercih edilmektedir. NKT ve tedaviye patolojik tam yanıt (pCR) ise HSK artırmaktadır. Bu çalışma Uludağ Üniversitesi Tıp Fakültesi Meme Cerrahi Kliniğinde ÜNMK tanısı ile ameliyat edilen hastaların lokal ve bölgesel rekürrens (LBR) oranlarına ve rekürrenssiz sağkalımına (LBRSK) etki eden faktörlerini ortaya konulması amaçlanmıştır. 2007-2020 yılları arasında ameliyat edilen hastaların demografik, klinik, patolojik verileri ve sağkalım oranları retrospektif olarak analiz edildi. İstatistiksel analizler SPSS v23 istatistik programı kullanılarak yapıldı. 173 hastanın 83’ü (%47,7) premenopozal ve yaş ortalaması 49,36+12,29 yıldı. Hastaların 106’sı (%63,8) lokal evre, 59’u (%34,1) lokal ileri evre ve 8’i (%4,6) metastatikti. 101 (%58,4) hastaya neoadjuvant, 69 (%40) hastaya adjuvant kemoterapi verildi. 122 (%70,5) hastaya meme koruyucu cerrahi, 99 (%57,2) hastaya sentinel lenf nodu örneklemesi yapıldı. Genel takip süresi ortanca değeri 57,5 ay içerisinde, 34 (%19,7) hasta yaşamını yitirdi. Ortanca rekürrens zamanı 33 ay içerisinde ise 16 (%11,8) hastada lokal nüks, 39 (%26,6) hastada sistemik nüks izlendi. 3-yıllık LBRSK oranı %47,3 izlendi. ÜNMK’de lokal ve sistemik nüks varlığında LBRSK oranları adjuvant ve neoadjuvant tedavide benzer izlenmiştir. NKT sonrası lokal ve rejyonel rekürrensi artıran ve rekürrenssiz sağkalımı azaltan en önemli faktör N3 hastalık ve premenopozal durum olarak izlenmiştir.

Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis

The current standard of care for resected early-stage triple negative breast cancer (TNBC) patients who did not receive systemic preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy (CT). A network meta-analysis (NMA) of randomized controlled trials (phase III) enrolling patients with resected stage I-III TNBC comparing adjuvant regimens was performed. Overall survival (OS) and disease-free survival (DFS) data were extracted. A total of 27 phase III clinical trials were selected including 15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of capecitabine into classic anthracycline/taxane-based combinations compared to anthracyclines with or without taxanes alone.

A 10 year service evaluation of the survival of 439 patients with early oestrogen receptor positive breast cancer who underwent initial OncotypeDX ® testing to guide adjuvant chemotherapy decisions

ObjectiveTo explore the long-term outcome of patients who underwent Oncotype DX® testing. The relationship between the RS, adjuvant treatments received, and clinical outcomes across the entire range of RS results are reported. Methods10-year Kaplan–Meier estimates for distant recurrence/BC-specific survival (BCSS) in this cohort. The analysis included 439 patients. The follow-up time ranged from 14 to 142 months. All analyses were performed using the SPSS v20. ResultsMore than half of patients had low RS (<18) (55.6%) and 15.3% had RS ≥ 31. Chemotherapy use was consistent with the RS with 4.4%, 7.1%, 28.0%, 71.4% and 91.0% receiving adjuvant chemotherapy in patients with RS < 11, 11–17, 18–25, 26–30, and ≥31, respectively. The overall chemotherapy rate was 27.6%. Distant metastasis free survival (DMFS) differed significantly (P < 0.001) between the RS groups with 10 year DMFS rates of 99% (SE +/- 0.01) in the RS<11, 97% (SE +/- 0.03) in the RS 11–17, 97% (SE +/- 0.02) in the RS 18–25, 85% (SE +/- 0.1) in the RS 26–30 and 74% (SE +/- 0.08) in the RS ≥ 31 group. Ten year breast cancer specific survival also differed significantly (P < 0.001) between the RS groups; this risk was 100% (no deaths from breast cancer reported in the first 10 years) in RS < 11, 95% (SE +/- 0.03) in RS 11–17, 94% (SE +/- 0.04) in RS 18–25, 93% (SE +/- 0.07) in RS 26–30, and 79% (SE +/- 0.07) in the RS ≥ 31 group. ConclusionsUse of Oncotype DX RS does guide the treatment decisions and correlates with the BCSS and disease-free survival for ER positive, Her2 negative, early-stage, node negative breast cancer patients.

Efficacy and safety of anlotinib-based treatment in metastatic breast cancer patients.

To evaluate the efficacy and safety of anlotinib-based treatment in metastatic breast cancer (MBC) patients with failure of standard treatment. We collected the medical data of 56 female patients with the diagnosis of MBC and had failed the standard treatment before. These patients received at least two cycles of anlotinib-based treatment as the second-line or beyond treatment between October 2019 and April 2022 in Jiangsu Cancer Hospital. The primary endpoint of our study was progression-free survival (PFS), and it was estimated with Kaplan-Meier. The second end points were disease control rate (DCR), objective response rate (ORR), and side effects. The median PFS time of a total of 56 patients was 5.7 months (95% CI, 3.17-8.22months). The ORR and DCR was 28.6% and 71.4%, respectively. In second-line, third-line, and beyond treatment, the median PFS was 11.7 months, 8.7 months, and 4.7 months, respectively. In different subtype of breast cancer, the median PFS was 5.6 months, 5.7months, and 6.4 months in human epidermal growth factor receptor 2 positive (HER2+), hormone receptor positive and HER2 negative (HR+/HER2-), and triple negative breast cancer (TNBC) patients, respectively. Most adverse effects were clinically manageable, and the most common events were platelet count decrease (35.7%), hand-foot syndrome (19.6%), diarrhea (19.6%), and fatigue (17.9%). The most common grade 3 and 4 adverse events were platelet count decrease (25.0%), diarrhea (7.1%), and oral mucositis (5.4%). Anlotinib-based treatment showed good efficacy and manageable toxicity in multi-line treatment of MBC patients who failed the standard treatment.

Clinical characteristics, risk factors, and outcomes in Chilean triple negative breast cancer patients: a real-world study.

Latin American (LA) studies on triple-negative breast cancer (TNBC) and their characteristics are scarce. This forces physicians to make clinical decisions based on data obtained from studies that include non-Hispanic patients. Our study sought to obtain local epidemiological data, including risk factors and clinical outcomes from a Chilean BC registry. This was a retrospective population-cohort study that included patients treated at a community hospital (mid-low income) or an academic private center (high income), in the 2010-2021 period. Univariate and multivariate analyses were performed to identify prognostic factors associated with survival. 647 out of 5,806 BC patients (11.1%) were TNBC. These patients were younger (p = 0.0001) and displayed lower rates of screening-detected cases (p = 0.0001) compared to non-TNBC counterparts. Among TNBC patients, lower income (i. e., receiving treatment at a community hospital) was associated with poorer overall survival (HR: 1.53; p = 0.0001) and poorer BC specific survival (HR: 1.29; p = 0.004). Other risk factors showed no significant differences between TNBC and non-TNBC. As expected, 5-year OS was significantly shorter on TNBC versus non-TNBC patients (p = 0.00001). In our multivariate analyses TNBC subtype (HR: 2.30), locally advanced stage (HR: 7.04 for stage III), lower income (HR: 1.64), or non-screening detected BC (HR: 1.32) were associated with poorer OS. To the best of our knowledge, this is the largest LA cohort of TNBC patients. Interestingly, the proportion of TNBC among Chileans was smaller compared to similar studies within LA. As expected, TNBC patients had poorer survival and higher risk for early recurrence versus non-TNBC. Other relevant findings include a higher proportion of premenopausal patients among TNBC. Also, mid/low-income patients that received medical attention at a community hospital displayed lower survival versus private health center counterparts.

159 (PB-072) Poster - Impact of lymphedema on health-related quality of life in early-stage breast cancer patients treated breast conserving therapy with or without sentinel lymph node biopsy: 2-year results from the randomized controlled trial BOOG2013–08

Background: The BOOG 2013-08 study examined non-inferiority of omission of the sentinel lymph node biopsy (SLNB) in clinically node negative cT1-2 breast cancer patients treated with breast conserving therapy (NCT02271828).1 This study explores whether omission of the SLNB results in a significant decrease in axillary morbidity rate and improved health-related QoL (HRQoL) at 6- 12- and 24 months post-surgery.

449P The study of androgen receptor status in triple negative breast cancer patients at Medical Oncology Department, Yangon General Hospital (YGH)

Breast cancer is the most common malignant tumor in women worldwide. Among the molecular subtypes of breast cancer, triple negative breast cancer (TNBC) is associated with worse prognosis and it lacks targetable hormonal receptor. In TNBC, androgen receptor (AR) positivity is about 25%-75% and would get potential benefit from anti-androgen therapy. The aims of this study are to know the occurrence of TNBC cases at Medical Oncology Department, YGH, and to know the AR status in TNBC cases.

Low TINAGL1 expression is a marker for poor prognosis in breast cancer.

Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. The median follow-up period was 12.0years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

Metronomic Chemotherapy is an Effective and Well Tolerated Treatment in Advanced Triple Negative Breast Cancer Patients: A Case Report of a Very Long Responder and Literature Review

Metronomic Chemotherapy is an Effective and Well Tolerated Treatment in Advanced Triple Negative Breast Cancer Patients: A Case Report of a Very Long Responder and Literature Review

PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan–Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan–Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.

Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2-Negative Postmenopausal Breast Cancer Patients.

Simple SummaryThe presence of immune cells within the tumor (TILs) indicates good prognosis for some aggressive breast cancer subtypes. However, less is known about TILs role within the hormone-responsive breast cancer (ER+/HER2−). These tumors represent up to 70% of all breast cancers and often exhibit long-term metastasis. TILs were quantified in tumor section samples from 763 postmenopausal women who received tamoxifen vs. no treatment and categorized into low, intermediate, or high. Among the ER+/HER2−, TILs were associated with poor prognostic variables but did not have prognostic value. High TILs indicate less benefit from tamoxifen. Interestingly, high gene expression of some TIL markers did indicate good prognosis even after adjusting for other clinical variables or were associated with less tamoxifen benefit. These results suggest that TIL markers could be used as prognostic, predictive indicators, and potential candidates for immunotherapy interventions after tamoxifen failure.The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (<10%), intermediate (10–39%), or high (≥40%). High TILs were associated with poor prognostic variables and good prognoses for all patients, but not within the ER+/HER2− group. Within the ER+/HER2− group, high gene expression of CD19 and PD-L1 and high IMMUNE1 score indicated good prognosis in multivariable analysis while high CD8 and CD19 gene expression and high IMMUNE1 score were associated with less tamoxifen benefit. These results indicate that within the ER+/HER2− subtype there could be subsets of patients where expression of specific TIL markers might be used to reveal candidates for immune therapy interventions upon failure of the endocrine therapy.