bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P2-14-27: Impact of surgery on survival in patients with stage IV breast cancer: A population-based study from the SEER database
Authors: Song C-G , Lin Y-X , Zhang J , Zeng Q , Chen M-Y , Chen L-L , Wang X-X , Chen Q-X
Published: May 2019

Surgical treatment for stage IV breast cancer remains controversial. Therefore, we aimed to further explore the impact of surgery on survival in patients with stage IV breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We selected 3,822 patients diagnosed with stage IV breast cancer from 2010 to 2012 in the SEER database who were divided into surgery and non-surgery groups. We assessed the breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups using Kaplan-Meier plots and Cox proportional hazard regression models. In addition, we performed stratification analyses of breast subtype, tumor size and status of distant metastasis to identify the effects of these factors on surgical outcomes. The median survival times were 30 and 24 months in the surgery and non-surgery groups, respectively. The Kaplan-Meier curves showed that the surgery group survived longer than the non-surgery group. The hazard ratios (HR) of the surgery group were 0.504 for BCSS and 0.507 for OS (P<0.001). Furthermore, patients in the surgery group still experienced significantly better survival than those in the non-surgery group when stratified according to breast subtype, tumor size and status of distant metastasis. Surgical treatment appears to be associated with improved survival in patients with stage IV breast cancer, independently of breast subtype, tumor size and status of distant metastasis.

Citation Format: Song C-G, Lin Y-X, Zhang J, Zeng Q, Chen M-Y, Chen L-L, Wang X-X, Chen Q-X. Impact of surgery on survival in patients with stage IV breast cancer: A population-based study from the SEER database [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 P2-14-27.
Abstract P3-01-06: Correlation of disseminated or circulating tumor cells with the OncotypeDX recurrence score
Authors: Tevis SE , Hall C , Meas S , Hwang R , Lucci A
Published: May 2019

Background: New biomarkers continue to emerge to predict the risk of recurrence in women with early stage breast cancer. A high OncotypeDX Recurrence Score (RS)® has been found to be associated with worse disease-free and overall survival in patients with early stage breast cancer. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in patients with breast cancer. We sought to evaluate the association between high RS and CTCs and DTCs.

Methods: We evaluated patients with hormone receptor positive, HER2 negative, node-negative invasive breast cancer from a prospective database from 1/2005 to 1/2017. RS was classified based on the new TAILORx study cutoff points as low (<11), intermediate (11-25), and high (>25). CTCs were assessed using CellSearch. For DTCs cytospin specimens of bone marrow aspirates, enriched for epithelial cells by density gradient separation, were immunostained using a pancytokeratin cocktail of antibodies, including AE1/AE3, CAM5.2, MNF116, cytokeratin 8 (CK8), and CK18. CTCs and DTCs were considered to be positive if one or more CTCs or DTCs were identified, respectively. Chi square analyses were utilized to evaluate for a relationship between OncotypeDX RS and CTCs or DTCs. Statistical analyses were performed in SPSS version 24 with p value <0.05 considered significant.

Results: Two hundred and thirty patients meeting the above criteria were identified from a prospective database, of which 106 had OncotypeDX testing results. Of the patients with available OncotypeDX data, 93 patients had CTC results and 60 patients had DTC results. CTCs were detected in the blood of 18/93 (19.4%) patients, while DTCs were detected in the bone marrow of 20/60 (33.3%) patients. Patients with high RS were not more likely to have CTCs as compared with patients who had low or intermediate RS (16.7% vs 19.8%, p=0.801). Similarly, high RS was not associated with the detection of DTCs, with DTCs present in 44.4% of patients with high RS, compared with 31.4% of patients with low or intermediate RS (p=0.443). In the subgroup of patients ≤50 years of age no associations were found between high RS and CTCs (p=0.720) or DTCs (p=0.151).

Conclusions: High OncotypeDX RS did not correlate with CTCs in the blood or DTCs in the bone marrow in our study.

Citation Format: Tevis SE, Hall C, Meas S, Hwang R, Lucci A. Correlation of disseminated or circulating tumor cells with the OncotypeDX recurrence score [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 P3-01-06.
Abstract P3-03-08: Not presented
Authors: Liang Y , Chen X , Zhan W , Zhu Y , Wu J , Huang O , He J , Zhu L , Li Y , Chen W , Shen K
Published: May 2019

This abstract was not presented at the conference.

Citation Format: Liang Y, Chen X, Zhan W, Zhu Y, Wu J, Huang O, He J, Zhu L, Li Y, Chen W, Shen K. 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 P3-03-08.
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

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 <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

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

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

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

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

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

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 (>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%) >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<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 >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

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

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

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

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.
Abstract P3-12-20: The use of new delineation tool “MIRADA”, step-by-step development and first results of its use in early and locally advanced breast cancer patients
Authors: Xu H , Arsene Henry A , Robillard M , Amessis M , Kirova YM
Published: May 2019

Objectives: To describe the practical procedure of implementation and optimization of delineation using “Mirada” software, as well as evaluation of the automatic segmentation for the daily practice of lymph nodes (LN) and OARs (organs at risk) in early as well as locally advanced stage breast cancer patients.

Methods: Forty patients' CT scans in treatment position were selected and re-contoured according to the ESTRO guidelines. The atlas of dataset was then created for automatic delineation. Thirty patients with breast/chest wall and lymph nodes regions irradiated were recruited for evaluation. With the same treatment position, the CT scan images were acquired and then contoured by the MIRADA system automatically as well as by the radiation oncologist manually (as the reference). The Conformity Index (CI) was used to evaluate the concordance between both of them.

Results: The mean time for manual contour was 24.1±5.1 mins and 26.4±2.8 mins for the LN and the OARs resp. All the volumes of interest were contoured using the software (including corrections) in 30 minutes, which reduced the time of delineation of target volumes and OAR by about 40%. Of the 30 cases evaluated, the mean CI of 5 principal OARs showed ≥ 0.8. While the automatic contour of LN was less satisfactory with mean CI of 0.43±0.1 (0.23-0.52).

Conclusions: For the breast cancer patients, the studied software permitted to save time for delineation with acceptable OAR contours. The improvement of LN regions contour is needed. More cases and further evaluation are needed for the system to realize its routine use.

Citation Format: Xu H, Arsene Henry A, Robillard M, Amessis M, Kirova YM. The use of new delineation tool “MIRADA”, step-by-step development and first results of its use in early and locally advanced breast cancer patients [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 P3-12-20.
Abstract P3-16-01: Responding at patient's time of need: Scaling rapid access to evidence-based treatment plans
Authors: Ramarajan N , Srivastava R , Begum F , Gupta S , Pramesh C , Badwe R
Published: May 2019

Background: Cancer patients worldwide feel intense anxiety, often racing to start treatments at non expert centers. Further, imbalanced oncologist to patient ratios (˜1600: 1.8 M in India, ˜23,000: 15M in USA), impedes access to expertise. We study the impact of rapid evidence based expert treatment plans in relieving patient anxiety. Navya, a health services technology, generates personalized treatment plans that maps within NCCN Resource Stratified Guidelines [SABCS 2017]. This is vetted on mobile by oncologists at tertiary centers like TMC NCG to provide expert opinion reports to patients. Since 2015, ˜19,457 patients from 57 countries have reached out for an online opinion. On the ground, 78% of patients received evidence based treatments recommended by Navya [ASCO 2017].

Methods: To assess impact of timeliness, a prospective series of patients (from Sep '17 to April '18) were asked: “Were you relieved to receive expert opinion report in [x] days?” “Does it matter to you to receive expert opinion report in 1 day?” To assess time savings, preliminary reports with treatment options from NCCN and TMC NCG guidelines were shared with patients who matched all guidelines criteria. Subsequently, expert opinion reports were shared as usual.

Results: 543/701 patients responded to phone follow-up. 97% [± 3.2] were relieved to receive expert opinion reports in 1-2 days (103/106) vs 83% [± 3.8 ] for 3+ days (365/437). Of those not relieved by 3+ day turnaround, 83% stated that it would matter to receive expert opinion reports in 1 day (60/72). The first 300 preliminary reports shared in median time of 3.37 hours, resulted in 90% time savings vs expert opinion reports. On 10% of the preliminary reports, experts added information such as de-/escalating therapy (18/31), and additional diagnostic tests (6/31).

Conclusions: Navya relieves patient anxieties by responding at the time of need with evidence based treatment plans. Scaling such health services technologies to patients worldwide is feasible.

Citation Format: Ramarajan N, Srivastava R, Begum F, Gupta S, Pramesh C, Badwe R. Responding at patient's time of need: Scaling rapid access to evidence-based treatment plans [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 P3-16-01.
Abstract P4-02-15: The effect of the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines in HER2 positivity rates among women with breast cancer in SEER registries
Authors: Wang XK , Hu N , Herget K , Cinbis BR , Gulbahce EH
Published: May 2019

Introduction: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) revised the HER2 testing guidelines in breast cancer (BC) which was published in December 2013, practically becoming effective in 2014. Since then, many studies reported a significant increase in HER2 positivity rate in BC. Although HER2 has been routinely evaluated in BC for over a decade, HER2 status was not included in SEER registries until 2010. The aim of this study is to look at the effect of the 2013 ASCO/CAP guidelines on HER2 status in the SEER database that captures approximately 28% of all cancers in the US.

Material and Methods. Using data from 18 SEER cancer registries between the years of 2010-2015 when HER2 status for breast cancers was available, women with invasive BC were identified and their HER2 status and race was recorded. The Chi-square test was used to test the significance between positive proportions before and after the new ASCO/CAP guidelines were effective. Logistic regression was used to test if the changes in positivity rate were the same among different races. All calculations were made after excluding cases with unknown/missing HER2 status.

Results: We identified 376,278 women diagnosed with invasive BC between the years 2010-2015. HER2 positivity before 2014 (2010-2013) was 14.4% compared to 15.6% after 2013 (2014-2015) (p<0.001). HER2 positivity increased in all races after 2013. There was no significant difference in the increase of HER2 positivity between whites and blacks after the new guidelines went into effect. Unknown/missing HER2 status continually decreased over the study period from 7.4% in 2010 to 5.3% in 2015. Overall unknown/missing HER2 was significantly different among races: 6.5% in whites; 7.1% in blacks; and 6.2% in other races (p<0.01).

Conclusion: Revised ASCO/CAP HER2 guidelines significantly increased HER2 positivity rates in SEER registries from 14.4% to 15.6% after implementation started in 2014. HER2 positivity increased in all races after 2013. Unknown/missing HER2 status is significantly different among different races. Blacks have highest unknown/ missing HER2 status in SEER registries.

Citation Format: Wang XK, Hu N, Herget K, Cinbis BR, Gulbahce EH. The effect of the 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines in HER2 positivity rates among women with breast cancer in SEER registries [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 P4-02-15.
Abstract P4-06-09: Withdrawn
Authors: Corsi F , Andreata F , Truffi M , Sorrentino L , D'Addio F , Monieri M , Gambaro A , Bellini M , Prosperi D , Mazzucchelli S
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Corsi F, Andreata F, Truffi M, Sorrentino L, D'Addio F, Monieri M, Gambaro A, Bellini M, Prosperi D, Mazzucchelli S. 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 P4-06-09.
Abstract P4-06-20: Delivering tumour antigens survivin and mucin-1 on virus-like particles for breast cancer immunotherapy
Authors: Kramer K , Braeden D , Young VL , Walker GF , Ward VK , Young SL
Published: May 2019

Breast cancer is the most frequently diagnosed cancer in women worldwide. Although there are a variety of treatment options available, breast cancer is a difficult disease to treat and many patients experience recurrence following treatment. We have previously shown that tumour antigens delivered on virus-like particles (VLP) induce a targeted anti-cancer immune response. In this study we investigated whether combining the two tumour antigens survivin and mucin 1 as vaccine targets can induce a superior anti-cancer immune response for breast cancer immunotherapy. VLP were designed to recombinantly express the murine survivin epitope. Following expression of Survivin-VLP, aberrantly glycosylated mucin 1 (MUC1) peptide was conjugated onto the Survivin-VLP using intracellular cleavable bis-arylhydrazone linking strategy. Western Blot analysis and electron microscopy confirmed Survivin-VLP expression and UV absorption confirmed conjugation of the MUC1 peptide to the Survivin-VLP. C57mg.MUC1 breast cancer cells were injected into the mammary fat pad of C57Bl/6 and MUC1 transgenic mice. Once tumours were palpable, mice were vaccinated with the Survivin-MUC1-VLP and controls of DPBS, VLP without antigen or VLP delivering either survivin or MUC1 antigen. Tumour growth and mouse survival were monitored for 80 days. Mice vaccinated with Survivin-MU1-VLP delivering both antigens showed enhanced survival (D78) compared to mice vaccinated with VLP delivering only one of the antigens (D66) and controls (D53). Delivery of two tumour antigens induced an enhanced anti-tumour immune response compared to delivery of single tumour antigens. The induction of multiple immune responses against different tumour antigens may apply additional evolutionary pressure upon tumours, prolonging the ability for tumours to develop resistance, or escape through the proliferation of a resistant subpopulation. The use of VLP for the delivery of multiple antigens and adjuvants represents a promising approach to improve cancer immunotherapy for breast cancer.

Citation Format: Kramer K, Braeden D, Young VL, Walker GF, Ward VK, Young SL. Delivering tumour antigens survivin and mucin-1 on virus-like particles for breast cancer immunotherapy [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 P4-06-20.
Abstract P4-07-02: Withdrawn
Authors: Katzenellenbogen BS , Guillen VS , Ziegler Y , Kim SH , Laws MJ , Zhao Y , Yasuda MA , Li Z , El-Ashry D , Katzenellenbogen JA
Published: May 2019

This abstract was withdrawn by the authors.

Citation Format: Katzenellenbogen BS, Guillen VS, Ziegler Y, Kim SH, Laws MJ, Zhao Y, Yasuda MA, Li Z, El-Ashry D, Katzenellenbogen JA. 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 P4-07-02.
Abstract P4-08-22: Impact of application of AJCC 8th edition on survival rate of the breast cancer
Authors: Kwon S , Yoon DS , Bae IE , Choi WJ , Choi IS , Lee SE , Moon JI , Sung NS , Park SM
Published: May 2019

Background

The AJCC 8 edition has changed much in comparison with the 7 edition. In addition to TNM stage, biologic marker (ER, PR, HER2), Histologic grade and multigene assays (oncotype Dx.) should be considered for staging. and it has been applied since January 1, 2018.

patients were recategorized and analyzed in order to know if this more complex classification helps to predict the real prognosis of the patients,

Method

We review patients who were diagnosed and treated as breast cancer at Konyang Universty Hospital. we studied retrospectively 582 patients who were followed up and were able to review.

Stage was classified according to AJCC 7th edition and AJCC 8th edition. survival rate of each stage were analyzed in both editions.

Result

Mean follow up period was 68.6 months. Total 582 patients were included. There was no change in the stage in 257 patients. In 195 patients, the stage was elevated and in 130 patients, the stage was changed down. When classified as AJCC 7th edition, the 5year-survival rate was 95.9% in stage I, 97.9% in stage II, 93.1% in stage III and 89.9% in stage IV. The survival rate of patients in stage I was lower than that of stage II. However, when the AJCC 8th edition was applied, the 5- year survival rate was 97.9% in stage I, 96.9% in stage II, 92.2% in stage III, and 89.9% in stage IV. In 8th edition, the patients in lower stage has higher survival rate.

Conclusion

The prediction of survival rate by stage was more accurate and the difference in survival rate of each stages was more clearly distinguished when The AJCC 8th edition was applied than AJCC 7th edition. AJCC 8th edition was reliable and useful for prediction of prognosis of breast cancer patient.

Citation Format: Kwon S, Yoon DS, Bae IE, Choi WJ, Choi IS, Lee SE, Moon JI, Sung NS, Park SM. Impact of application of AJCC 8th edition on survival rate of the 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 P4-08-22.
Abstract P4-08-28: Clinical risk prediction models for breast cancer: A review of models developed between 2010 and 2018
Authors: Siesling S , Hueting T , Tip B , Mentink R , Koffijberg E
Published: May 2019

Background:

Clinical prediction models provide insight in the probability of a specified event happening based on the personal characteristics of the patient. Predicted probabilities support physicians in tailoring clinical decisions to the patients needs. Throughout the past decades, the amount of developed prediction models has grown, yet the application of these models in daily medical practice falls behind. It is currently uncertain how many prediction models exist to support decision making in breast cancer care and exactly which decisions may be supported using prediction models. This study aimed to identify all developed prediction models on breast cancer care and to assess the clinical applicability of the models in the target breast cancer population.

Methods:

A literature search was performed to identify developed risk prediction models published from January 2010 up to June 2018. Models predicting breast cancer related events were included. Identified models were assessed on the reported transparency and reproducibility and incorporated in the online platform for prediction models: Evidencio. Clinical applicability of the models was assessed using a digital implementation of the Dutch breast cancer guideline called Oncoguide. Models were assigned to location in the guideline where they may support clinical decisions.

Results:

A total of 91 studies describing the development of 142 prediction models were identified. Thorough assessment showed that 31 models were reported in full having the description of all the necessary parameters to reproduce the underlying statistical formula and were incorporated in Evidencio.com. For 95 models the formula could be derived through the presented nomogram, table, or online calculator. The remaining 16 models were lacking information to construct any method to predict the outcome of an individual patient and could therefore not be used in practice.

Conclusion:

A total of 142 prediction models were developed between January 2010 and June 2018. The overall quality of reporting was poor as 111 models were not described transparently. All identified models were assigned to the location in the guideline of which the model may support clinical decision making. Further assessment is necessary on the clinical impact and validity of the models in the Dutch population before implementing them in the guideline.

Citation Format: Siesling S, Hueting T, Tip B, Mentink R, Koffijberg E. Clinical risk prediction models for breast cancer: A review of models developed between 2010 and 2018 [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 P4-08-28.