bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-03-22: Prognostic impact of axillary lymph node status after neoadjuvant chemotherapy for patients with breast cancer
Authors: Nakamura R , Yamamoto N , Miyaki T , Itami M 
Published: May 2019

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 &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.
Abstract P3-03-27: Can we select patients suitable for targeted axillary dissection after neoadjuvant chemotherapy who originally presented with involved axillary nodes?
Authors: Nagy ES , Whisker L , Asgeirsson K 
Published: May 2019

Abstract
Introduction:
The current recommended management for patients with involved lymph nodes at diagnosis of breast cancer is to perform an axillary node dissection after receiving neoadjuvant chemotherapy (NAC), regardless of response. A number of studies have proposed de-escalation of this practice by performing sentinel node biopsies and targeted axillary dissections in those with response to chemotherapy. We have audited our practice to assess the safety of introducing management change.
Methods:
Cancer data was collected between 2014 and 2018 for patients who had NAC and further selection criteria for those with lymph node involvement at diagnosis and subsequently underwent NAC. Assessment of radiological response at NAC completion, tumour hormone receptors and HER2 status along with axillary nodal response on final histopathology were reviewed to assess whether patients can be stratified to less extensive axillary management.
Results:
290 patients underwent NAC, 60 of whom had nodal involvement at diagnosis:
- All had USS axilla, MRI at baseline and completion of NAC
- All 60 node positive patients underwent axillary clearance, as per current local protocol
- Out of those 60 node positive patients, 39 had breast conserving surgery, whilst 21 patients had mastectomy
- 20 (33%) patients showed complete radiological response (CRR) on MRI in both breast and nodes
- 23 (38%) patients achieved pathological complete response (PCR) in their nodes
- 17 patients showed both CRR and PCR
- 4 patients showed CRR but did not achieve PCR:
o patient 1: 1 macromet / 7 nodes - NEG/NEG/NEG
o patient 2: 1 micromet / 14 nodes - POS/POS/POS
o patient 3: 7 macromet / 10 nodes - POS/POS/NEG
o patient 4: 5 macromet / 19 nodes - POS/POS/NEG
- Large volume of nodal disease remained in 2 patients with POS/POS/NEG despite CRR
Conclusion:
MRI can be safely and reliably used in patients who show CRR with TNBC and HER2+ cancers to select patients for de-escalating axillary surgery. Caution in those patients with POS/POS/NEG cancers as MRI may show CRR but large volume disease in nodes may still persist. Further prospective audit of de-escalating treatment will be essential to ensure locoregional control and long-term disease-free survival outcomes.
Citation Format: Nagy ES, Whisker L, Asgeirsson K. Can we select patients suitable for targeted axillary dissection after neoadjuvant chemotherapy who originally presented with involved axillary nodes? [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 P3-03-27.
Abstract P3-03-31: Is sentinel lymph node biopsy necessary in all patients with early breast cancer?
Authors: Yoon KH , Lee KB , Lee H , Lee J , Kim JY , Park HS , Park S , Kim SI , Cho YU , Park B-W 
Published: May 2019

Abstract
Background and objectives : Since the results of the American College of Surgeons Oncology Group Z0011 published, the criteria for applying axillary lymph node (ALN) dissection was relaxed among early breast cancer patients who were scheduled for breast conserving surgery, adjuvant chemotherapy therapy, and adjuvant radiation therapy. SLNB criteria may be established if pathologic nodal status can be predicted. The aim of this study was to develop a nomogram for preoperative prediction of axillary node metastasis.
Methods: The records of 1650 patients with T1, T2 primary invasive breast cancer who were treated between January 2013 and September 2016 were selected from the medical database of Yonsei University (Seoul, South Korea). Those whom a preoperative diagnosis of axillary node metastases were excluded. Two nomogram that predicted three or more axillary metastasis and one or more axillary metastasis were developed using a binary logistic regression model with a training cohort. Internal validation was carried out adopting bootstrap method by validation cohort 500 times resampling.
Result: A total of 82 (4.8%) patients had three or more ALNs metastasis. Three hundred seventy five (17.4%) patients had one or more ALNs metastasis. Axillary metastasis was associated with Preoperative ALN suspicious image findings, clinical tumor size, Number of neoplastic foci, estrogen receptor status, Ki-67 expression, tumor marker. The nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (AUC 0.79, 95% CI, 0.73–0.85), (AUC 0.71, 95% CI, 0.67–0.74) and calibration fit.
Conclusion:Our nomogram might help predict the ALN metastasis in breast cancer patients. Patients with a low probability of ALN metastasis could be spared SLNB.
Citation Format: Yoon KH, Lee KB, Lee H, Lee J, Kim JY, Park HS, Park S, Kim SI, Cho YU, Park B-W. Is sentinel lymph node biopsy necessary in all patients with early 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 P3-03-31.
Abstract P3-03-36: Not presented
Authors: Khan RN , Baig M , Mohtasham S , Khan A , Pervaiz A 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Khan RN, Baig M, Mohtasham S, Khan A, Pervaiz A. Not presented [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 P3-03-36.
Abstract P3-05-02: Not presented
Authors: Gruber JJ , Chen J , Geller B , Jager N , Lipchik AM , Snyder MP 
Published: May 2019

Abstract
This abstract was not presented at the conference.
Citation Format: Gruber JJ, Chen J, Geller B, Jager N, Lipchik AM, Snyder MP. Not presented [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 P3-05-02.
Abstract P3-08-02: Withdrawn
Authors: Harano K , Wang Y , Masuda H , Lim B , Parinyanitikul N , Lee H-J , Seitz RS , Morris SW , Bailey DB , Hout DR , Rao A , Lucci A , Tripathy D , Krishnamurthy S , Ueno NT 
Published: May 2019

Abstract
This abstract was withdrawn by the authors.
Citation Format: Harano K, Wang Y, Masuda H, Lim B, Parinyanitikul N, Lee H-J, Seitz RS, Morris SW, Bailey DB, Hout DR, Rao A, Lucci A, Tripathy D, Krishnamurthy S, Ueno NT. Withdrawn [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 P3-08-02.
Abstract P3-08-16: Age's importance in early breast cancer: Oncotype Dx results in patients ≤40 years
Authors: Ruiz R , Namuche F , Morante Z , Aguilar A , Urrunaga D , Ziegler G , Chavez Mac Gregor M , Leon M , Gomez H 
Published: May 2019

Abstract
Background
The 21-gene recurrence score (RS) predicts the benefit of adjuvant chemotherapy (CT) in ER-positive HER2-negative breast cancer (BC) and has been validated in population where women under 40 are underrepresented.Young BC pts are more likely to receive adjuvant chemotherapy (CT) in addition to endocrine therapy (ET). Our objective was to assess the RS results in young (≤40 yo) vs older (&gt;40 yo) pts and evaluate the impact of age on clinical decision-making according to RS categories.
Methods
We retrospectively reviewed electronic medical files of all patients with early stage hormone receptor BC for whom RS was available between 2007 and 2017 in 3 specialized cancer centers. We used the Mann-Whitney and Chi-squared tests to assess differences between age group. Similarly, we evaluated the association between age groups and treatment, within each ODx category. To determine if age was associated with CT use in the low risk category, a logistic regression model was constructed.
Results
A total of 551 pts were included, 53 (9.6%) ≤40 yo and 498 (90.4%) &gt;40 yo. No statistical differences were found between the younger and older groups in T (p=0.874), N (p=0.794), stage (p=0.188), or grade (p=0.791). Young patients underwent radical surgery more frequently than their older counterparts (41.5 vs 25.7%, p=0.014). Statistically significant differences were also observed in ER mean, which was lower in the younger group (80 vs 90%, p&lt;0.001). The median RS result was significantly higher in the younger group (19 vs 16, p=0.009). Also, high-risk recurrence score category was significantly more frequent in the younger group (22.6 vs 9.2%, p=0.009). In the intermediate-risk category there were no differences in the proportion of patients who received CT according to age groups (p=0.484). In the low-risk category, 28.0% of patients ≤40 years vs 11.3% of patients &gt;40 years received CT (p=0.037).
Conclusions
Our results indicate that RS tends to be higher in patients with BC ≤ 40 yo and that the frequency of high-risk RS is significantly higher in the younger group, suggesting biological differences between groups. 28% of young patients with low-risk RS from our cohort are overtreated. Based on these results, it should be considered to develop a test adjusted to the age of the patients.
Citation Format: Ruiz R, Namuche F, Morante Z, Aguilar A, Urrunaga D, Ziegler G, Chavez Mac Gregor M, Leon M, Gomez H. Age's importance in early breast cancer: Oncotype Dx results in patients ≤40 years [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 P3-08-16.
Abstract P3-09-07: The role of MLK4 amplification in progression of triple negative breast cancer
Authors: Prelowska MK , Mehlich D , Lazniewski M , Kaminska K , Gorczynski AS , Korwat A , Sokolowska O , Golab J , Biernat W , Plewczynski D , Brognard J , Nowis D , Marusiak AA 
Published: May 2019

Abstract
Mixed Lineage Kinase 4 (MLK4) is a serine/threonine kinase that plays a role in a variety of cellular processes, including migration, apoptosis and proliferation. It belongs to the family of MAP3 kinases, which regulate the activity of specific MAPKs (mitogen-activated protein kinases). MLK4 is the least described member of the family and it was proved to act as a functional MAP3 kinase that activates the JNK, ERK and NFκB pathways. The rationale of this project is based on the recent data showing gene amplification and mRNA upregulation of MLK4 in invasive breast carcinoma at the frequency of 23%. Here, we performed a series of experiments aiming to characterize the role of MLK4 in breast cancer development and progression. We started from identification of breast cancer cell lines that express high endogenous level of MLK4. Since clinical data indicated that MLK4 expression was higher in triple-negative breast cancer (TNBC), comparing to other breast cancer subtypes, we decided to further study the role of MLK4 in TNBC. We have generated cell lines with doxycycline-inducible knock-down of MLK4, HCC1806 and HCC1599, and we found that MLK4 depletion resulted in reduced cell proliferation. We also observed that the knock-down of MLK4 in these conditions caused the reduction in size of the spheroids. Moreover, we noticed that when MLK4 is depleted in HCC1806 cells, the migration and invasion was significantly impaired. Lastly, our results of immunohistochemistry in samples from breast cancer patients showed that higher levels of MLK4 in TNBC samples significantly correlated with the occurrence of lymph node metastasis. Currently, we are investigating molecular pathways such as JNK, MEK/ERK and NF-κB, that might be affected by knock-down of MLK4. Collectively, our findings indicate that high levels of MLK4 promote aggressive phenotype of breast cancer cells, by increasing their migratory and invasive potential.
Citation Format: Prelowska MK, Mehlich D, Lazniewski M, Kaminska K, Gorczynski AS, Korwat A, Sokolowska O, Golab J, Biernat W, Plewczynski D, Brognard J, Nowis D, Marusiak AA. The role of MLK4 amplification in progression of triple negative 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 P3-09-07.
Abstract P3-10-25: Clinicopathologic factors associated with pCR to neoadjuvant anti-HER2-directed chemotherapy
Authors: Meisel JL , Suo A , Taylor CE , Zhang C , Li X 
Published: May 2019

Abstract
Background: While the use of neoadjuvant therapy has become the standard of care in certain locally advanced breast cancers, questions remain regarding the optimal chemotherapeutic regimen as well as biologic and patient-specific predictors of pathologic complete response. In this study, we examined patient and tumor-specific characteristics associated with increased prediction of pathologic complete response (pCR) to neoadjuvant anti-HER2-directed chemotherapy.
Methods: 204 patients who received neoadjuvant anti-HER2-directed chemotherapy at our institution from 2006-2016 were included in this retrospective study. Univariate analyses were performed to analyze the relationships of multiple clinical and pathologic features to pCR rate. Multivariate analysis was also performed to evaluate the relative impact of specific pathologic characteristics on pCR rate.
Results: Among 204 patients with HER2 overexpressing breast cancers treated with neoadjuvant chemotherapy, 52.7% achieved pCR. Pathologic complete response was positively associated with high tumor grade (61.0% grade 3 in pCR group vs 39.0% in non-pCR group, P=0.23) and high Ki67 index (mean Ki67 59.1 in pCR group vs 47.4 in non-pCR; P= 0.015). It was also associated with HER2 IHC 3+ (57.1% in pCR group vs 42.9% in non-pCR, p=0.029), HER2 copy number (mean copy number 16.8 in pCR group vs 12.4 in non-PCR, p-0.004), and HER2/CEP 17 ratio (mean ratio 6.42 in pCR group vs 5.17 in non-pCR; P= 0.046). Rates of HER2 FISH positivity were equal in the pCR and non-pCR groups (50.8% vs 49.2%, p=0.062). Multivariate analysis demonstrated that higher Ki67 index and higher HER2/CEP17 ratio are significant predictors of pCR after adjusting for other covariates (odds ratio for Ki67 1.03 (1.06-1.49), p=0.002; for HER2/CEP17 ratio OR 1.26 (1.06-1.49), p=0.009).
Conclusions: In HER2 positive breast cancers, a higher Ki67 index as well as higher HER2/CEP17 ratios are associated with an increased pCR rate and may be useful as predictors of response prior to neoadjuvant therapy. Our results also demonstrate HER2 IHC to be a stronger predictor than HER2 FISH of response to upfront therapy. Larger studies would be useful as this association, if confirmed, may have relevance to clinical practice.
Citation Format: Meisel JL, Suo A, Taylor CE, Zhang C, Li X. Clinicopathologic factors associated with pCR to neoadjuvant anti-HER2-directed chemotherapy [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 P3-10-25.
Abstract P3-10-29: tRNA-derived fragments as novel predictive biomarkers for trastuzumab-resistant breast cancer
Authors: Sun C , Li W , Wu H , Huang X , Li J , Fu Z , Tang J , Yin Y 
Published: May 2019

Abstract
Background: Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resistance is still unknown.
Methods:We detected the levels of tRNA-derived fragments expression in normal breast epithelial cell lines, trastuzumab-sensitive and -resistant breast cancer cell linesusing high-throughput sequencing.qRT-PCR was conducted to validate the differentially expressed fragments in serums from trastuzumab-sensitive and -resistant patients. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the power of specific tRNA-derived fragments.Progression-free survival (PFS) was analyzed using Cox-regression.
Results:Our sequence results showed that tRNA-derived fragments were differentially expressed in the HBL-100, SKBR3, and JIMT-1 cell lines. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were found significantly upregulated in trastuzumab-resistant patients compared to sensitive individuals, and the ROC analysis showed that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were correlated with trastuzumab resistance. In a multivariate analysis, higher levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression were associated with significantly shorter PFS in patients with metastatic HER-2 positive breast cancer.
Conclusion: Our results suggest that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN play important roles in trastuzumab resistance. Patients with high levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression benefitted less from trastuzumab-based therapy than those that express lower-levels of these molecules. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN may be potential biomarkers and intervention targets in the clinical treatment of trastuzumab-resistant breast cancer.
Citation Format: Sun C, Li W, Wu H, Huang X, Li J, Fu Z, Tang J, Yin Y. tRNA-derived fragments as novel predictive biomarkers for trastuzumab-resistant 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 P3-10-29.
Abstract P3-12-17: Intraoperative radiotherapy (IORT) after neoadjuvant chemotherapy in patients with breast cancer– Experience in the Cancer Institute of Lima-Peru
Authors: Cotrina JM , Galarreta JA , Pinillos MA , Vilchez S 
Published: May 2019

Abstract
Background
Intraoperative radiotherapy (IORT) is a treatment technique that allows the surgical bed to be irradiated in the same surgical act after breast-conserving surgery, in some cases as a single treatment and in others as a boost complemented with external radiotherapy. There are studies that have shown their non-inferiority with respect to conventional external radiotherapy, taking advantage of administration time, costs and side effects.
Methods
In this study, the IORT (INTRABEAM) was used as treatment in patients who received neoadjuvant treatment with chemotherapy who had a good response and met the criteria to be included (no tumor or tumors less than 3 cm, unifocal tumors, no skin involvement after treatment).
Out of a total of 255 cases of IORT performed in recent years, 42 were studied, those who received neoadjuvant chemotherapy from April 2014 to April 2018 and who completed the treatment.
Results
The average age was 47.9 years (29-72), 59.5% were between 40-49 years old and 11.4% were under 40 years old. 61.9% were stage II and 38.1% stage III. The diameter of the most used applicator was between 3-3.5 cm (56.8%) and the average irradiation time was 20 mins (12-46 mins). All received external RT. 67.6% received on average 25 sessions and 32.4% received 15 sessions. There were 64.2% luminal (luminal A 7.1%, luminal B 38.1%, luminal B HER2 (+) 19%), 7.1% with ER/PR(-) HER2(+) and 28.6% ER/PR(-) HER2(-). 38% patients had complete pathological response in the primary tumor. Of the 42 patients treated, 37 had a follow-up of more than 6 months. 3 (7.1%) had recurrence, 2 local and 1 local and distant (EC IIIC). Disease-free survival at 12, 24 and 36 months was 97.2%, 90.5% and 90.5% and the overall survival was 100%, 100% and 92.3% respectively.
Clinical Stages / ImmunophenotypesClinical StagesN (%)ImmunophenotypeN (%)IIA12(28.6)Luminal A3(7.1)IIB14(33.3)Luminal B16(38.1)IIIA7(16.7)Luminal B HER2(+)8(19.0)IIIB8(19.0)ER/PR(-) HER2(+)3(7.1)IIIC1(2.4)ER/PR(-)HER2(-)12(28.6)
Disease Free SurvivalMonths122436DFS97.2%90.5%90.5%
Conclusion
The IORT (INTRABEAM) used as a boost in patients with breast cancer and neoadjuvant treatment who complete complementary external RT, is a safe procedure, with low recurrence rate, it is easy to perform with a good tolerance, shorter time of treatment and with fewer side effects.
Citation Format: Cotrina JM, Galarreta JA, Pinillos MA, Vilchez S. Intraoperative radiotherapy (IORT) after neoadjuvant chemotherapy in patients with breast cancer– Experience in the Cancer Institute of Lima-Peru [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 P3-12-17.