Triple Negative Group Research Articles

Abstract P5-06-21: Prognostic and predictive value of PML in the ETNA study and the TCGA

Abstract Background. Although long considered a tumor suppressor gene, PML (promyelocytic leukemia) also plays tumor-promoting functions in specific contexts. In vitro and in vivo studies have demonstrated that PML is upregulated by HIF-1α transcriptional activation in triple-negative breast cancer (TNBC) cells and it is implicated in promoting metastasis downstream of HIF-1α. This pro-metastatic function of PML is inhibited by arsenic trioxide, a pharmacological compound currently in use in acute promyelocytic leukemia. However, the clinical relevance of PML expression in BC has not been extensively investigated. In this study, we evaluated the association of PML expression with clinic-pathological factors and outcome (pathological complete response -pCR- and risk of recurrence) in the ETNA trial, and risk of recurrence in the TCGA. Methods. In the ETNA study (NCT01822314) 695 patients with HER2-negative breast cancer (BC) were randomized to receive neoadjuvant paclitaxel or nab-paclitaxel followed by 4 cycles of an anthracycline regimen. In the ITT study population, the two treatments did not show significantly different rates of pCR nor different Event-Free Survival (EFS) (Gianni JAMA Oncol 2018, Gianni ASCO 2019). A central histologic assessment of ER, PgR, HER2 status and Ki67 was mandatory. We evaluated PML expression by immunohistochemistry using the continuous histoscore (H-score) on pre-treatment core biopsies. The H-score is generated from the estimation of the percentage of cells with no (0), light (1+), moderate (2+) and strong (3+) intensity staining, and the corresponding score is generated with the following algorithm: [1 × (% cells 1+) + 2 × (% cells 2+) + 3 × (% cells 3+)]. We evaluated the association of PML with clinic-pathological features and clinical outcomes (pCR and EFS) in triple negative (TN) and in LuminalB-like (ER+ and/or PgR+, Ki67≥14%) groups. We also investigated the association between PML mRNA expression (RNA-seq) and DFS in HER2-negative BC (TN, n=192; ER+/HER2-, n=702) in the TCGA dataset. Results. In the ETNA study, PML was successfully assessed and valuable in 491 pts (70.6%). The average PML expression was 126.3 (median 120, range 0-295). In the ETNA trial, TNBC showed the highest expression of PML (p<1.0E-10). Within LumB-like tumors, the group with intermediate proliferation (Ki67 14-20%, LumB-int) had higher PML expression than the high proliferation group (Ki67>20%, LumB-high) (p=0.0005). However, within the LumB-high group, higher proliferation (Ki67>40%) showed a higher expression of PML (p=0.025), suggesting a non-linear relationship between PML and proliferation in luminal tumors. In LumB-high, PML was higher in PgR-negative tumors (p=1.0E-5). Finally, PML showed a positive association with higher stromal tumor-infiltrating lymphocytes (sTILs) both in LumB-like and TN group (p=0.019 and p=0.001, respectively). PML expression was not significantly associated with pCR and risk of recurrence in LumB-like nor in TN BC.In the TCGA dataset also PML expression was highest in the TN group (p<1.0E-10). No association was found between PML expression and risk of recurrence in any molecular subgroup. Conclusions. PML expression assessed by IHC in the ETNA trial was not predictive of likelihood of pCR nor of risk of recurrence in LumB-like and TN breast cancer. PML mRNA expression was not prognostic in TN and LumB-like tumors also in the TCGA dataset. Some interesting associations with biological features emerged which warrants biological interpretation of the complex role of PML in breast cancer. Supported in part by an unrestricted grant from Celgene Sarl, Swizerland Citation Format: Stefania Zambelli, Chanel Smart, Giampaolo Bianchini, Isabella Sassi, Mauro Mansutti, Antonio Anton, Lourdes Calvo, Giancarlo Bisagni, Begona Bermejo, Martina Uggè, Barbara Galbardi, Vladimir Semiglazov, Marc Thill, Jose Ignacio Chacon, Arlene Chan, Serafin Morales Murillo, Isabel Alvarez, Ainhara Lahuerta, Patrizia Zucchinelli, Claudio Doglioni, Pinuccia Valagussa, Ignasi Tusquets, Luca Gianni, Rosa Bernardi. Prognostic and predictive value of PML in the ETNA study and the TCGA [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-21.

Abstract P3-08-60: Patterns of development and prognostic factors in central nervous system metastasis according to breast cancer subtypes

Abstract Introduction: Central nervous system (CNS) metastasis are detected in approximately 10-30% of breast cancer (BC) patients, being associated with poor prognosis despite local and systemic therapeutics available. In the current study, we aimed to evaluate the association between BC subtypes and CNS metastasis development and prognosis. Methods: Retrospective analysis of 258 BC patients’ records with pathological and/or radiological documented CNS metastasis, treated at a Cancer Center between 2003-2019, median follow-up of 61 months (range: 0-351). For analysis purpose, three BC subtypes were considered according to hormone receptor status and HER-2 expression: luminal, HER-2 positive and triple negative. Survival was evaluated by Kaplan-Meier method and groups were compared with log-rank test. Independent prognostic factors were identified using Cox regression model. A p value < 0.05 was considered statistically significant. Results: Ninety four (42%) patients had HER-2 positive, 87 (39%) luminal and 41 (19%) triple negative disease. The median time between the diagnosis of BC and the detection of CNS metastasis was significantly shorter in triple negative group (18 months) compared to the others (HER-2 positive: 31 months; luminal: 54 months; p=0.001), and CNS was more often the first site of recurrence (with or without concomitant extracranial disease progression) in this group (triple negative: 25 (61%) vs. HER-2 positive: 31 (33%) vs. luminal: 27 (31%); p=0.002). Most of the patients had parenchymal metastasis (n=245), being exclusively parenchymal in 227 (88%), and 31 (12%) had leptomeningeal (LM) disease, that was isolated in 13 (5%). More than half (n=136) had multiple (>3 lesions) CNS metastasis, without differences between BC subtypes. Among the patients with LM disease, 17 (68%) had luminal tumors, 5 (20%) HER2-positive and 3 (12%) triple negative (p=0.007). Forty five patients (17%) were treated with surgery for CNS metastasis, with similar proportions between BC groups. In the patients submitted to CNS surgery, the concordance between primary tumor and metastasis subtype was higher in HER-2 positive (73%) compared to 57% in triple negative and 50% in luminal groups (p=0.004). After CNS involvement, 62% (n=24) of patients with triple negative disease did not receive any systemic therapy, compared to 44% (n=37) in luminal and 33% (n=29) in HER-2 positive groups (p=0.010). Median survival after CNS metastasis documentation was longer in HER-2 positive group (27 months vs. luminal: 18 months vs. triple-negative: 14 months, p=0.004) and also in patients submitted to surgical resection of CNS metastasis (38 months vs. 6 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastasis (HR 0.62, 95% CI: 0.47-0.84, p=0.002), regardless the therapeutic strategy. Conclusions: Pattern of CNS metastasis development and prognosis varies according to BC subtype. The association between LM disease and luminal tumors should be explored in future studies. Treatment modalities also play a decisive role in the prognosis of this patients, therefore, new and effective therapeutic strategies are needed. Citation Format: IoIanda Vieira, Miguel Abreu, Tiago Alpoim, Isabel Pereira, Susana Sousa, Isabel Azevedo, Machado Carvalho, Deolinda Pereira. Patterns of development and prognostic factors in central nervous system metastasis according to breast cancer subtypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-60.

Correlation Between Gamma-Glutamyl Transferase Activity and Glutathione Levels in Molecular Subgroups of Breast Cancer.

The gamma-glutamyl cycle catalyzed by gamma-glutamyl transferase (GGT) plays an important role in glutathione (GSH) homeostasis in the cell. In cells continuously exposed to the drug, the main phase of the enzymatic detoxification is the conjugation of the drug with GSH catalyzed by glutathione-S-transferase (GST). Conjugation of drugs with GSH is the first step in the development of chemotherapeutic drug resistance. In this study, we aimed to investigate the relationship between GGT and GSH in molecular subgroups of breast cancer patients. Serum GGT activity and GSH levels for patients diagnosed with breast cancer (n=58) and healthy controls (n=8) were measured by a spectrophotometric method and a colorimetric kit, respectively. GGT activity was significantly higher in the total patient group and in the molecular subgroups than those in the control groups (p<0.05). Serum GSH levels were higher in the patient groups compared to controls without reaching statistical significance (p>0.05). GGT activity was positively correlated with GSH levels in the total patients and healthy controls (p<0.001 and p<0.05, respectively). There was also a positive correlation between GGT activity and GSH levels in Luminal A, HER2-positive (Human epidermal growth factor receptor 2), and Triple-negative groups (p<0.05). This is the first study showing the relationship between GGT and GSH in molecular subgroups of breast cancer. An increase in GGT activity may affect intracellular GSH synthesis. Therefore, having a correlation between GGT and GSH in some molecular subgroups may affect the course of treatment in these patients.

Characteristics and clinical outcome of pT1a-b node-negative breast cancer.

OBJECTIVE:Tumor size, along with other clinicopathological characteristics, has a prognostic role in breast cancer. Recurrence risk tends to rise as tumor size increases. Early T-stage portends a good prognosis. We aimed to investigate the recurrence-free interval rates of T1abN0 group of early breast cancer.METHODS:Patients diagnosed with pT1a and T1b, lymph node metastasis-negative breast cancer were included in the study. Clinicopathologic characteristics including recurrence, distant metastasis, and final status of the patients were obtained retrospectively from the patient files.RESULTS:A total of 84 patients included. Twenty-six patients (31%) had T1a and 58 patients (69%) had T1b tumors. The 5-year distant relapse-free survival (DRFS) rate of T1ab tumors was 95.2%. The DRFS rate of T1a tumors was 96.2%, while the rate of T1b tumors was 94.8% (p=0.555). The 5-year RFS rate of T1ab tumors was 90.5%. The RFS rate of T1a tumors was 84.6%, whereas the rate of T1b tumors was 93.1% (p=0.359). The 5-year DRFS rate of hormone receptor positive group was 97%, Her-2 positive group was 81.8%, and triple negative group was 100% (p=0.041). The 5-year RFS rate of the hormone receptor positive group was 97%, Her-2 positive group was 72.7%, and triple negative group was 57.1% (p=0.001).CONCLUSION:The results of the study provided that both T1a and T1b tumors have a good and similar prognosis.

Role of Magnetic Resonance Imaging in the Evaluation of Breast Cancer Response to Neoadjuvant Chemotherapy.

The aim of the study was to evaluate whether residual tumor assessment by magnetic resonance imaging (MRI) after neoadjuvant chemotherapy (NACT) is fundamental for a successive surgical strategy. We collected 55 MRIs performed after NACT. Pathological response rate was 20%. MRI's sensitivity, specificity, PPV and NPV were 50%, 88%, 54% and 86%, respectively. We observed a high variability between the different subgroups, with high number of false positives in luminal A/B tumors. Triple negative and HER2+ tumors had almost the same specificity and sensitivity (81% and 50%). Nevertheless, in the HER2+ group, PPV was greater than that in the triple negative group (71% and 33% respectively) and the NPV of the triple negative group was greater than that of the HER2+ one (90% and 64%, respectively). Statistical analysis showed a weak but significant correlation between MRI and pathological assessment of residual tumor dimension. The present study, confirms literature data about MRI accuracy in diagnosing HER2+ and triple negative tumors, but suggests caution in case of luminal tumors' evaluation.

Mutation profile in Indian primary myelofibrosis patients and its clinical implications.

Background:Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by abnormal proliferation of megakaryocytes, bone marrow fibrosis, and extramedullary hematopoiesis. We did mutation profile of 50 patients of PMF and tried to correlate it with initial clinical presentation of these patients.Materials and Methods:All new and follow up patients who were diagnosed as PMF based on WHO 2016 definition of PMF were included. Mutation profile of these patients including JAK2 V617F, JAK2 exon 12, CALR and MPL mutations was done and all clinical, demographic and laboratory details were recorded.Results:Total 50 patients were enrolled out of which 29 were males and 21 were females. Out of these patients, 32 (64%) were JAK2 positive, 13 (26%) were CALR positive, 1 (2%) were MPL positive and 4 (8%) were triple negative. As compared to JAK2+ve patients and triple negative group, CALR positive patients were younger, had lower total leucocyte count, larger spleen size, lower dynamic international prognostic scoring system (DIPSS) score and higher grade of fibrosis of marrow.Conclusion:This study depicts that incidence of JAK2 and CALR mutations in Indian PMF patients is fairly similar to that in rest of the world. CALR positive patients have better clinical parameters at presentation and have better prognosis as compared to JAK2 positive patients.

Relationship between 18-FDG-PET/CT and Clinicopathological Features and Pathological Responses in Patients with Locally Advanced Breast Cancers.

We investigated the relationship between the maximum standardized uptake value (SUVmax) of whole-body positron emission tomography/computed tomography (PET/CT) performed before treatment and the demographical and histopathological features in locally advanced breast cancer (LABC), as well as the role of PET/CT in the evaluation of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Fifty-one LABC patients who received NAC in our center between 2011 and 2015 were retrospectively analyzed. Basal PET/CT was performed in all the patients before NAC. The SUVmax levels and demographical and histopathological results were compared. The relationship between the SUVmax values after NAC and pathological responses were evaluated. The mean age of the patients was 49 (32-69) years. PET/CT performed after NAC showed complete response in 20 patients (39.2%), partial response in 28 patients (54.9%), stable disease in 2 patients (3.9%), and progressive disease in 1 patient (2%). There was no significant difference between the mean SUVmax values of the patients according to age (>50 and ≤50 years), menopausal status, tumor localization, clinical stage, and grade. The mean SUVmax value was higher in the triple-negative group than those in the HER2 positive and luminal groups. There was a significant difference in the SUVmax values between the group that achieved pCR after NAC and the group that could not achieve pCR (SUVmax value for breast 2.92 vs. 0.30; p=0.01; SUVmax value for axilla 1.5 vs. 0.0, p=0.02). The SUVmax values are independent of demographical features. There was a significant relationship between the pCR and SUVmax values after NAC. PET/CT could be useful in the evaluation of patients to predict the biological characteristics of tumors.

Radiomics of Multiparametric MRI for Pretreatment Prediction of Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer: A Multicenter Study.

We evaluated the performance of the newly proposed radiomics of multiparametric MRI (RMM), developed and validated based on a multicenter dataset adopting a radiomic strategy, for pretreatment prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer. A total of 586 potentially eligible patients were retrospectively enrolled from four hospitals (primary cohort and external validation cohort 1-3). Quantitative imaging features were extracted from T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging before NAC for each patient. With features selected using a coarse to fine feature selection strategy, four radiomic signatures were constructed based on each of the three MRI sequences and their combination. RMM was developed based on the best radiomic signature incorporating with independent clinicopathologic risk factors. The performance of RMM was assessed with respect to its discrimination and clinical usefulness, and compared with that of clinical information-based prediction model. Radiomic signature combining multiparametric MRI achieved an AUC of 0.79 (the highest among the four radiomic signatures). The signature further achieved good performances in hormone receptor-positive and HER2-negative group and triple-negative group. RMM yielded an AUC of 0.86, which was significantly higher than that of clinical model in two of the three external validation cohorts. The study suggested a possibility that RMM provided a potential tool to develop a model for predicting pCR to NAC in breast cancer.

Preoperative prognostic nutritional index predicts clinical outcomes in patients with lower-grade gliomas

Objective: To investigate the prognostic values of preoperative prognostic nutritional index (PNI) in patients with lower-grade gliomas. Methods: In the study, 379 patients with pathological diagnosis of lower-grade gliomas were enrolledwhich were confirmed in The First Affiliated Hospital of Zhengzhou University (2011-02 to 2016-05). Kaplan-Meier method was used to calculate the survival rates. log-rank was used to calculate the differences in group. Cox regression model was used to conduct multivariate analysis. Results: The cutoff value of PNI was 46.70. The median survival time of PNI≤47.80 and PNI>47.80 subgroups were 46.76 and 67.37 months with statistical significance (P<0.001). High PNI predicted a better survival rate. Multivariate survival analysis demonstrated that low PNI was an independent risk factor to evaluate the prognosis of glioma patients. In lower-grade gliomas, high PNI predicted better survivals in TERT mutation only (P=0.003) and triple-negative group (P=0.007). Conclusion: In lower-grade gliomas, low PNI predicts worse survivals and PNI have differential prognostic significances in molecular groups of lower-grade gliomas.

Four versus six cycles of docetaxel and cyclophosphamide in early breast cancer.

e12047 Background: ABC trials established the use of non-anthracycline containing regimen, docetaxel and cyclophosphamide (TC) as adjuvant therapy in early breast cancer. In clinical practice, TC is commonly used in Stage I Triple Negative (TN) and Stage I,II Hormone positive breast cancer. However, no specific recommendations exist in literature, regarding the number of cycles that can be used. i.e. TC4 vs TC6. Our aim, was to determine if TC4 is non-inferior to TC6 when used as adjuvant therapy in early breast cancer. Methods: We retrospectively reviewed 143 patients who were diagnosed with early breast cancer, between 2007 to 2017, at our institution who had received either TC4 or TC6 as adjuvant therapy. The number of cycles the patients received were based on provider preference. The two groups (TC4, TC6) were compared in regard to stage of cancer at diagnosis based on AJCC 7th edition-stratified by TNM staging for hormone positive and T staging only for TN, grade of adverse events, recurrence and death from breast cancer. Median follow up was 5 years. Results: Out of the 143, 102(71.3%) received TC4 and 41(28.7%) received TC6. Among the hormone positive, 42 were stage I and out of which 32(76.2%) received TC4 and 10(23.8%) received TC6 and there were 24 stage II patients, out of which 17(70.8%) received TC4 and 7(29.2%) received TC6. Among the TN group, there were 64 who were T1, out of which 45(70.3%) received TC4 and 19(29.7%) received TC6, while there were 12 T2 patients, out of which 7(58.3%) received TC4 and 5(41.7%) received TC6. Recurrence of breast cancer was seen in 5(4.9%) in TC4 and 3(7.3%) in TC6, p=0.569. Death due to breast cancer was seen in 2(1.9%) in TC4 and 1(2.4%) in TC6, p=0.856. Adverse events were seen in 86(84.3%) in TC4 and 39(95.1%) in TC6,p=0.078. Adverse events of Grade 3 or higher were seen in 10(9.8%) in TC4 and 11(26.8%) in TC6, p=0.09. Conclusions: In this limited series, TC4 appears to be equally effective to TC6, with fewer adverse events of any grade and lower incidence of Grade 3 or higher side effects which was statistically significant. Although the proportion of patients who received TC 4 were higher in our series, the percentage of patients who received TC6 was higher in stage II for hormone positive and T2 for TN when compared to Stage 1 and T1 respectively. We also found a higher percentage of recurrence and death due to breast cancer in TC6 which was not statistically significant and this likely a reflection of the fact that as mentioned above patient with a higher stage at diagnosis tended to receive 6 cycles as compared to 4 cycles and therefore had a higher chance of recurrence in the future.

Low-dose metronomic chemotherapy (LDMC) as an efficient treatment option in metastatic breast cancer: Results of an exploratory case-control study.

e12578 Background: There is a growing importance of low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control-analysis we compared the efficacy of LDMC and conventional chemotherapy in MBC. Methods: Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two patients who received conventional chemotherapy. Age, number of chemotherapy lines and metastatic lesions as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate greater than 24 weeks (DCR). Secondary endpoints were DCR in subgroups (number of chemotherapy lines, number of different metastatic lesions and HR status), progression-free survival (PFS) and duration of response (DoR). Results: A total of 35 cases and 70 controls entered the study. 31% patients with LDMC and 26% patients with conventional chemotherapy showed DCR (p = 0.644). Among younger patients DCR was 41% in LDMC vs. 30% in the control group (p = 0.534). In addition, DCR was achieved in 35% vs. 27% patients with ≤ 2 chemotherapy lines (p = 0.560) and in 36% vs. 20% patients with ≤ 2 different metastatic lesions (p = 0.168), respectively. In the triple negative group 30% LDMC vs. 5% control patients showed DCR (p = 0.095). PFS was 12.0 vs. 13.5 weeks (p = 0.415), DoR was 26.5 vs. 20.5 weeks (p = 0.628), respectively. Conclusions: In this retrospective case-control study we demonstrated a similar efficacy of LDMC compared to conventional chemotherapy in the treatment of MBC. Moreover, no significant differences were found in the subgroups studied. Therefore, the concept of LDMC may also be a treatment option in both younger and non-heavily pre-treated MBC patients who do not need rapid remission.

Supervivencia en cáncer de mama por subtipo mediante inmunohistoquímica: Un estudio retrospectivo

Breast cancer subtype classification according to hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry is the standard practice for therapeutic decision making. To design future studies information on characteristics and survival of each subtype is essential. We conducted a retrospective study to analyze clinical and pathologic features as well as survival data according to breast cancer immunohistochemistry subtype. There were 211 women with a RH(+)/HER2(-) breast cancer subtype, 53 HR(+)/HER2(+), 16 HER2(+) and 23 HR(-)/HER2(-), with a median overall survival in months of 39 (20.5-62.7), 42 (25.5-65), 42 (13.7-67.7) and 26 (11-78), respectively, for a 3.7 hazard ratio of death (95% Confidence Interval [CI]: 1.3-10.3) for the triple negative group as compared to the HR(+)/HER2(-) group (p = 0.01). HR positive subtypes by immunohistochemistry where most frequent and showed a greater overall survival compared to the triple negative subtype.

Impact of body mass index on breast cancer subtypes in Iranian women

Background: The incidence of obesity as one of the risk factors of breast cancer (BC) is increasing dramatically. Our objective was to evaluate the association between body mass index (BMI) and three subtypes of BC in Iranian women. Materials and Methods: In this retrospective study, BC patients' information was recorded by referring to their medical records in the Cancer Institute of Imam Khomeini Hospital, Iran, from 2015 to 2017. The data of 374 patients were entered into the study, and tumor data were classified into three groups by molecular markers (human epidermal growth factor receptor 2 [HER2] enriched, triple negative, and luminal). Results: Luminal subtype comprised the majority (71.1%) of all diagnosed BC patients. The proportion of obese women was higher in triple-negative group (35.3%), although the differences between three subtypes of BC were not statistically significant (P = 0.30). Multivariate logistic among cases only, considering luminal as the comparison group, indicated a positive association between age of menarche and HER2-enriched subtype (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 0.99–1.41, P = 0.07) and also suggested a reverse association between age at time of diagnosis and triple-negative subtype (OR = 0.97, 95% CI: 0.95–1, P = 0.09) with borderline significance. Conclusion: We did not find any statistically significant differences in BMI between three subtypes of BC. It seems that there is a correlation between triple-negative subtypes of BC in Iranian population and obesity. However, further studies with larger sample size are needed.

Abstract P3-03-22: Prognostic impact of axillary lymph node status after neoadjuvant chemotherapy for patients with breast cancer

Abstract BACKGROUND: Patients were stratified by final pathological axillary status: ypN0, ypN1, pN0 or pN1. The prognostic impact of lymph node involvement after neoadjuvant chemotherapy (NAC) for breast cancer is not straightforward. The aim of this study was to compare overall survival (OS) between pathologically node-positive T1,T2 T3 breast cancer patients treated with NAC, with ypN0 or ypN1 and those treated without NAC with pN0 or pN1. METHODS: A total of 3903 consecutive patients with operable breast cancer were prospectively identified at our institution between April 2006 and December 2017. Patients with suspicious axillary LN of breast cancer were assessed using preoperative imaging, underwent fine-needle aspiration cytology or core needle biopsy. The patients in this study were divided into four groups as follows: the ER(+), the ER(+)/HER2(+) , the HER2(+) and the Triple negative (TN) group. We evaluate the prognostic impact of the ypN0, ypN1 (with one to three positive lymph nodes after NAC), pN0 and pN1 with no NAC. The main outcome measures DFS and OS were analyzed using Kaplan–Meier survival analysis. Result A number of 270 and 3633 patients were included for NAC and non NAC, respectively. Pathologic nodal status was ypN0 in 58%, ypN1 in 42% for NAC and pN0 in 76%, pN1 in 24% of patients for non NAC. Overall, 10-year DFS and OS was 81%, 93% in ypN0, 67%, 80% in ypN1, in 90%, 97%, in pN0 and 83%, 94% in pN1 (p &amp;lt;0.001). In subgroup analysis, 10-year DFS of ypN0, ypN1, pN0 and pN1 was 86%,77%,95% and 80% in the ER group, 91%,56%,93%,and 76% in the ER/HER2 group,89%,55%,91% and 80% in the HER2 group, 85%,59%,92% and 80% in the TN group. 10 years DFS for the ER group were significantly different between ypN0 and pN0 (HR, 2.42 (1.03–4.86, p = 0.04) but were not significantly different between ypN0 and pN0 for the ER/HER2 group (HR 3.58 (0.2–6.88, p = 0.66), for the HER2 group (HR 2.6 (0.78–7.65, p = 0.10) and for the TN group (HR 1.22(0.56–2.38, p = 0.58), respectively). In all group, DFS for ypN1 was inferior to ypN0. Conclusions In the ER group treated with NAC, DFS for ypN0 be inferior to pN0 with adjuvant treatment. In the HER2, the ERHER2 and the TN group treated with NAC, ypN0 is similar to pN0 with adjuvant chemotherapy. Axillary nodal status ypN1 in each subgroup is associated with a less favorable prognosis compared to ypN0. In conclusion, the HER2 or TN group is highest for predicting ypN0, shown to be most prognostic of long-term survival similar to the patients with pN0. They could be omitted the axillary dissection. Citation Format: Nakamura R, Yamamoto N, Miyaki T, Itami M. Prognostic impact of axillary lymph node status after neoadjuvant chemotherapy for patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-22.

Recurrence in early breast cancer: Analysis of data from 3,765 Australian women treated between 1997 and 2015

BackgroundEvidence suggests recent improvements in outcome in early breast cancer (EBC). AimTo analyse recurrence in women with EBC from our region from 1997 to 2015. MethodsWe analysed recurrence in 3,765 women with EBC. Median follow up was 83·0 months. 62·5% had a symptomatic presentation. 81·8% were hormone receptor positive and 38·5% were node positive. Lymphovascular invasion (LVI) was present in 24·3%. Of the 2,686 women entered from 2002 onwards tested for HER2 status, 72·7% had a luminal tumour, 15·2% had a HER2+ tumour and 12·1% had a triple negative (TN) tumour. ResultsRecurrence occurred in 459 (12·2%), predominantly in distant sites (71·7%). In women entered from 2002 onwards, the five and 10 year recurrence rates were significantly lower in the luminal group than the HER2+ and the TN groups. Few recurrences occurred in HER2+ and TN cancers after 36 months. On multivariate analysis the following were associated with a significantly increased risk of recurrence: nodal involvement (p < 0·0001), tumour grade (p < 0·0001), symptomatic presentation (p < 0·0001), presence of LVI (p = 0·001), non-luminal tumour type (p < 0·0001) and tumour size >50 mm (p = 0·02). ConclusionThe recurrence rate in this series was much lower than in previous older series. Lymph node involvement, tumour grade, symptomatic presentation, presence of LVI, non-luminal tumour type and tumour size (>50 mm) were associated with an increased risk of recurrence. We strongly recommend that clinicians include the presence of LVI and symptomatic presentation as well as the other established tumour factors, when assessing the risk of recurrence in women with EBC.

Prognostic Value of BCL2 in Women Patients with Invasive Breast Cancer

Background:Breast cancers are heterogeneous, making it essential to recognize several biomarkers for cancer outcome predictions especially in young women where the classical prediction parameters are not suitable. The goal from this study is to evaluate the impact of B cell lymphoma 2 (BCL2), P53 and Ki-67 proteins expression on survival in young women patients with invasive ductal carcinoma.Patients and methods:Samples and clinical data from 238 patients were collected between 2003 and 2017. They were selected according to 2 criteria: age ≤40 years old and most of them are affected by an Invasive Ductal Carcinoma. We evaluated BCL2, P53 and ki-67 expression by immunochemistry test, and then we assessed correlations of these biomarkers expression with patient’s clinicopathological characteristics and survival.Results:Triple negative breast cancer group showed a high frequency among our cohort but we emphasize an almost equitable distribution among all molecular groups. Contrary to other studies which reported that luminal A was correlated with better prognosis, our analysis demonstrated that luminal A is correlated with the Scarff, Bloom and Richardson (SBR) grading 2 or SBR grading 3. To better investigate the prognosis, we analyze three biomarkers known by their impact on physiopathology behavior on breast cancer BCL2, ki-67and P53. BCL2 is the more relevant one, it was correlated with molecular subtypes (p=0.0012) and SBR grading (p=0.0016). BCL2 seems to be the good prognostic biomarker related to survival (p=0.004) with a protective role among patients when endocrine therapy is not provided and Lymph Node (LN) involvement is positive (p=0.021, p=0.000 respectively).Conclusions:The classical prognostic parameters based mainly on the molecular classification in breast cancer seem insufficient in the case of young women. BCL2 protein expression analysis provides a better prognostic value. BCL2 should be clinically associated in current practice when young women specimens are diagnosticated.

Triple-Negative Myeloproliferative Neoplasms Vs. Calr, JAK2 or MPL-Mutated Myeloproliferative Neoplasms: Distinct Molecular Characteristics

Background: We compared the clinical, cytogenetic, molecular features, and telomere lengths of patients with triple negative MPN and MPN with any of CALR, JAK2 or MPL mutations.Methods: Target capture sequencing of 87 genes and molecular cytogenetic studies were performed in 61 Korean patients with MPN. Also, we searched the newly reported mutations and novel mutations in triple negative MPN [JAK2-G335D (germline), JAK2-F556V, JAK2-G571S (germline), JAK2-V625F (germline), MPL-T119I, MPL-S204F/P, MPL-E230G, MPL-V285E (germline), MPL-R321W (germline), MPL-Y591D, MPL-S505N and MPL-W515R]. We compared clinical and molecular characteristics between two groups. Additionally, we performed telomere quantitative FISH for 48 patients' samples and measured telomere/centromere ratios of them.Results: Among 61 patients, 13 patients showed mutations in CALR, 34 in JAK2, and 3 in MPL. All of JAK2 mutation and CALR mutation site were reported sites, but 2 among 5 mutation site of MPL were novel mutation [D128N, D261Y]. Twelve patients showed triple negative (7 of PMF 7, 2 of ET, and 3 of MPN-U) - they showed 8 different mutation sites among 6 different genes (ASXL1, DNMT3A, NPM1, POLG, SRSF2, and ZMYM3). NPM1, POLG, and ZMYM3 mutations were seen only in triple negative patients. NPM1 mutation was significantly higher in triple negative MPN (P=0.0301). In telomere length study, there was no statistical difference between triple negative group (T/C ratio mean 12.5) and CALR, JAK2 or MPL mutated group (T/C ratio mean 10.0). Although, MPN patients with telomere length shorter than normal control's lower 10% (7.04) showed poor prognosis (P=0.0045).Conclusions: Patients with triple negative MPN are characterized by high frequency of NPM1 mutation and less number of somatic mutations. Since the mutational analysis for diagnostic purposes is limited to exons 14 of JAK2, exon 10 of MPL and exon 9 of CALR at present, search for JAK2 and MPL mutations in other sites are essential in triple negative MPNs.Keywords: Myeloproliferative neoplasms, next-generation sequencing, triple negative MPN, chromosome, FISH, telomere [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Is Breast Cancer Problem in India Worse Than That of the West? Reflection of Analysis of Breast Cancer Molecular Subtyping from Tertiary Cancer Care Center in Northern India

Breast cancer in India is rapidly expanding overtaking cervical cancer in terms of incidence as well as mortality. Indian women with breast cancer are younger, premenopausal and a large proportion of patients present at advanced stages. Considering breast cancer to be a complex disease demonstrating heterogeneity at clinical and histopathological levels, breast cancer in the Indian population could be biologically dhistology and receptor status characterization ifferent from those of the west. We attempt to study the clinical and pathological aspects of breast cancer and its correlation with biomolecular subtyping with comparison to the western population in order to find a pattern of differences. All patients diagnosed and treated in the Department of Surgical Oncology, King George Medical University, Lucknow, UP, from the period of August 2014 to August 2016 are included. Clinical and histopathological data was recorded. A total of 355 patients were analyzed. Average age of patients with disease was 45.3 years. The premenopausal group consists of 52% of patients. Mostly patients presented in locally advanced stage. Triple-negative disease was associated with higher grade of disease (p < 0.0001) and higher rates of lymphovascular invasion (p = 0.040), pericapsular invasion (p = 0.005), and extranodal spread of disease (p < 0.001).This subgroup was significantly higher in premenopausal patients (p = .016). Disease-free survival was lower in triple-negative group. As compared to the western population, the breast cancer in India presents in younger, premenopausal, multiparous, and breast feeding women. Molecular subgrouping reveals that about 60% of the patients are hormone negative. Forty-three percent of patients were triple negative. It appears to be that breast cancer in India is a different subset from the western world in having different molecular signatures that translate into distinct clinical and histopathological subgroup.

Phase II Study of S-1 Combined With Low-Dose Docetaxel as Neoadjuvant Chemotherapy for Operable Breast Cancer Patients (N-1 Study)

BackgroundTo improve the pathological complete response (pCR) rate, we devised new neoadjuvant chemotherapy. Efficacy and safety of the oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical Co, Tokyo, Japan) combined with low-dose docetaxel (S-1+DOC) were evaluated. Patients and MethodsPatients were treated with docetaxel (40 mg/m2 intravenously on day 1) and S-1 (40 mg/m2 orally twice per day on days 1-14) every 3 weeks for 4 cycles. In accord with the Response Evaluation Criteria In Solid Tumors version 1.1 criteria, the patients who showed a complete response (CR) underwent surgery, and those who achieved a partial response (PR) underwent 4 more cycles of S-1+DOC. Patients who achieved stable disease (SD) or progressive disease (PD) received EC (epirubicin and cyclophosphamide) or HT (trastuzumab and paclitaxel) according to their HER2 status. The primary end point was the pCR rate. ResultsNinety-four patients entered the study. After 4 cycles of S-1+DOC, CR was noted in 5 patients, PR in 57, SD in 18, and PD in 3. Of the patients who achieved SD and PD, 12 received EC, and 9 received HT. Among the 83 assessable patients, the pCR rate was 34.9%, and the response rate was 80.7%. The pCR rates were 19.5% in the luminal type group, 53.8% in the luminal HER2 group, 46.1% in the HER2 group, and 50.0% in the triple-negative group. ConclusionThe S-1+DOC regimen in this study could be well tolerated and a new candidate neoadjuvant chemotherapy in operable breast cancer patients. It is also expected to be effective even in patients with luminal type disease. However, further randomized control trials are needed to ascertain whether pCR can contribute to favorable outcomes.

Triple Negative Breast Cancer, Clinicopathologic Study of Egyptian Patients, NCI Experience

AbstractBackground: Triple negative breast cancer category is a challenging group of breast cancer. It needs more detailed clinical and pathological studies.Aim of Study: To study the clinicopathologic characteristics of triple-negative breast cancer of Egyptian patients.Patients and Methods: A retrospective study was done included 59 women with triple negative breast cancer collected from Pathology Department at NCI, Cairo University, Egypt. Clinical data and pathological data were revised, then follow-up of the cases with a median follow-up time 40.5 months (range: 8-67).Results: Most cases were equal or below 50 years old, post-menopausal, and unilateral. According to pathological characters, majority of cases represented grade 2, T2, positive lymph nodes, and stage 2. As regards outcome three cases underwent recurrence, seven cases underwent metastasis, and two cases show metastasis and recurrence. At the end of the study 44 cases were alive, ten died, and five show lost follow-up. There was a significant relationship found between grade and DFS, as well as OS with grade, stage, occurrence of metastasis and node positivity.Conclusion: Triple negative breast cancer group were more noticed among age group less than 50 years, with tendency to express high grade, large tumor size, high stage and node positivity, with significant relationship between grade and DFS, as well as OS with grade, stage, occurrence of metastasis and node positivity.