bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P3-05-20: A study on amount, localization and immune phenotype of tumor-infiltrating lymphocytes in different subtypes of breast cancer
Authors: Popovska SL , Dimitrova PD , Dineva TB
Published: February 2018

Objective: The aim of the study was to investigate the localization, amount and type of lymphocytic infiltrate, found in different molecular subtypes of breast cancer (BC).

Methods: Retrospectively, 100 cases of invasive BC were analyzed and immunohistochemicaly (IHC) stratified in four subtypes (Luminal A and Luminal B-like, HER2-positive, and triple negative (TN). The percentage of stromal areas occupied by tumor-infiltrating lymphocytes (TILs) was assessed for H&E slides. The samples were IHC-stained for CD3, CD4, CD8, CD20 and FoxP3. The immunophenotyped lymphocytes - intratumoural and stromal, were separately counted, semi-quantitatively graded and further analyzed.

Results: A total of 10% of all tumors were lymphocyte-predominant BC. Intratumoral and stromal TILs were predominantly CD3+T-lymphocytes. High counts of all subtypes TILs - intratumoral and stromal, were most common for TNBC and HER2-positive BC.

In TNBC, the intratumoral CD3+TILs are significantly related to CD8+ (p=0.002) and FoxP3+ phenotype (p=0.010). In HER2 BC, the intratumoral and stromal CD3+ TILs were significantly related to FoxP3+ phenotype (p = 0,035 and p= 0.011, respectively).

Conclusion:CD3+T-cell mediated immunity, especially the one related to CD8+ and FoxP3+ lymphocytes was the leading one in antitumor response in BC, and high count of intratumoral and stromal lymphocytes predominated in TN and HER2-positive BC.

Key words: Breast cancer, tumor-infiltrating lymphocytes, CD3, CD4, CD8, CD20, FoxP3.

Citation Format: Popovska SL, Dimitrova PD, Dineva TB. A study on amount, localization and immune phenotype of tumor-infiltrating lymphocytes in different subtypes of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-20.
Abstract P3-06-05: Not presented
Authors: Croucher PJP , Franovic A , Ballinari D , Gasparri F , Giorgini L , Whitley P , Valsasina B , Erlander MG
Published: February 2018

This abstract was not presented at the symposium.
Abstract P3-06-06: Human endogenous retrovirus TROJAN promotes triple negative breast cancer progression and represents a potential therapeutic target
Authors: Jin X , Xu X-E , Jiang Y-Z , Shao Z-M
Published: February 2018

Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. We used RNA-Seq to analyze the transcription level of each HERV loci across the genome in eight pairs of triple negative breast cancer (TNBC) and normal breast tissues. We identified one LTR70, which we dubbed TROJAN, was a TNBC related HERV. We also found that HERVs could not be researched as families because each members from the same family had different expression patterns in TNBC. TROJAN promoted proliferation and invasion in TNBC cells and indicated poor outcomes in patients. Here, we confirmed that TROJAN regulated the progression of TNBC through multiple mechanisms, with ZMYND8, a metastasis-repressing factor, being one of the targets of TROJAN. TROJAN could bind to ZMYND8, promoting its degradation through ubiquitin-proteosome system, and downregulated the transcription level of EGFR, thus stimulating the metastasis of TNBC. The association of TROJAN, ZMYND8, and EGFR was subsequently confirmed in clinical samples. Furthermore, our study verified that the therapeutic delivery of antisense oligonucleotides targeting TROJAN significantly suppressed metastasis of TNBC in vivo. In conclusion, TROJAN promotes the progression of breast cancer and serves as a potential therapeutic target in TNBC.

Citation Format: Jin X, Xu X-E, Jiang Y-Z, Shao Z-M. Human endogenous retrovirus TROJAN promotes triple negative breast cancer progression and represents a potential therapeutic target [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-06.
Abstract P3-06-11: Withdrawn
Authors: Hamy A-S , Val de Lièvre C , Laas E , Darrigues L , Priour M , Guerin J , Balezeau T , Livartowski A , Pierga J-Y , Escalup L , Asselain B , Rouzier R , Lae M , Decroze D , Pinheiro A , Laurent C , Reyal F
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P3-07-11: Withdrawn
Authors: Chung AH , Leisner T , Alcedo K , Parise LV
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P3-08-15: Not presented
Authors: Bautista R , Rodríguez OA , Dehesa AZ , Miranda AH
Published: February 2018

This abstract was not presented at the symposium.
Abstract P3-09-01: Withdrawn
Authors: Pollán M , Lope V , Castelló A , Mena-Bravo A , Amiano P , Aragonés N , Fernández-Villa T , Guevara M , Dierssen T , Fernández-Tardón G , Castaño-Vinyals G , Marcos-Grajera R , Moreno V , Salas-Trejo D , Díaz-Santos M , Kogevinas M , Pérez-Gómez B , Priego-Capote F
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P3-10-10: Withdrawn
Authors: Kandhare PG , Williams CP , Nakhmani A , Burkard ME , Azuero A , Halilova KL , Pisu M , Bhatia S , Forero A , Rocque GB
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P3-12-11: Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model
Authors: Veitch ZW , Khan OF , Tilley D , Kostaras X , King K , Lupichuk S , Tang P
Published: February 2018

Background: Patient adherence to adjuvant hormonal therapy for breast cancer (BC) is correlated with improved survival. Recent publications have demonstrated ethnic disparities in adjuvant hormone adherence (AHA) for privatized healthcare models.

Objective: To identify disparities in AHA for BC patients within a universal healthcare system in Alberta, Canada.

Methods: Patients diagnosed from 2007-2014 with stage I-III, ER+/HER2- BC receiving adjuvant FECD or DC chemotherapy and at least one month of adjuvant hormonal therapy in Alberta, Canada were retrospectively assessed. Hormone monotherapy (tamoxifen, AI), switch strategies (tam to AI), and treatment duration were collected. Compliance was assessed with central pharmacy data. Patient ethnicity was identified using patient first/last and parental last name via Onolytics® ethnographic software. Ethnicity was further verified using a centrally collected place of birth. Age, AJCC stage, psychiatric diagnoses (mood, bipolar), and comorbidity were collected. Log rank and Chi squared were used to assess difference between adjuvant hormonal therapy for variables at 1, 2, and 5 years. Log rank p-values at 2 years are reported.

Results: A total of 2,399 ER+ patients were included for analysis. AHA was non-significant for ethnicity (p=0.797), comorbidity (p=0.623), psychiatric disorders (p=0.145), or elderly cohorts (p= 0.814). AHA by stage was significant with stage III > II > I (p=0.004) having the highest compliance rates. AHA was highest for planned hormonal switch strategies (p=0.004) compared to monotherapy.

Hormone Adherence RatesCharacteristicsNo. of Patients% AdherenceEthnicity  Caucasian211891.6Asian15293.4Middle Eastern/African9593.7Hispanic2491.7Age  <65207791.8>6534192.1Comorbidity  096191.21-3134392.2>311493Psychiatric Dx  Yes31189.7No210792.1Stage  I45388.3II151292.1III45394.5Hormone Strategy  Monotherapy173190.9Switch68794.2

Conclusion: AHA is not dependent on ethnicity, age, comorbidity, or psychiatric diagnosis in a universal healthcare model. Conversely, higher rates of AHA are seen with planned switch strategy compared to monotherapy, contradictory to the BIG I-98 trial. Patients with higher stage, and thus higher risk of BC recurrence have increased adherence compared to their low risk counterparts. Reinforcement of AHA for low/moderate risk BC patients, in addition to tamoxifen to AI switch strategies may improve overall adherence.

Citation Format: Veitch ZW, Khan OF, Tilley D, Kostaras X, King K, Lupichuk S, Tang P. Disparities in adjuvant hormone adherence in breast cancer patients within a universal healthcare model [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-12-11.
Abstract P4-02-05: Diagnostic value of breast MRI in evaluating total extent of disease when non-calcified DCIS is present in stereotactic core biopsy samples
Authors: Sheth D , Bao J , Abe H , Jaskowiak N
Published: February 2018

PURPOSE

To compare the extent of disease as seen on mammography, breast MRI and final surgical pathology in all patients with non-calcified DCIS identified on stereotactic core biopsy. Can MRI provide useful diagnostic information to the surgeon when mammographically occult DCIS is present.

METHOD AND MATERIALS

All patients with stereotactic core biopsies performed at the University of Chicago from 2010 to 2017 were retrospectively reviewed. Patients with pathology demonstrating DCIS in non-calcified cores on stereotactic biopsy were further selected based on whether they had a subsequent breast MRI and definitive surgical treatment. A total of 76 patients met these criteria. All patients undergoing stereotactic core biopsy had at least six 9-gauge cores removed, all of which were radiographed and separated based on whether calcifications were present or absent. Select patients with documented DCIS in the non-calcified cores had a MRI. All patients with MRI underwent a routine diagnostic protocol consisting of one pre- and five post-contrast bilateral, fat suppressed T1 sequences along with a non-fat suppressed T2 sequence. Final surgical treatment was subsequently determined and performed by the breast surgeon.

RESULTS

76 women met all criteria for this study. In 16/76 (21%) of the cases, MRI revealed greater extent of disease than was detected via mammography, and led to change in management in half of those cases (8/76 - 11%). In all 16 of these cases, final surgical pathology confirmed the MRI-detected extent of disease. In 52/76 (68%) of the cases, MRI confirmed the extent of disease detected on mammography and final surgical pathology. In 8/76 (11%) of the cases, MRI showed little to no abnormal enhancement at site of mammographically detected calcifications, even though final surgical pathology confirmed presence of residual disease.

CONCLUSION

The presence of non-calcified DCIS in stereotactic core biopsy samples raises the suspicion for the presence of mammographically occult disease. Breast MRI performed in this setting shows that in majority (82% -68/76) of the cases, MRI can either confirm or even advantageously reveal greater extent of disease than was initially detected on mammography. Furthermore, there can be a change in management due to the breast MRI findings.

CLINICAL RELEVANCE/APPLICATION

Breast MRI can be a useful diagnostic tool for the surgeon when non-calcified DCIS is present in stereotactic core biopsy samples.

Citation Format: Sheth D, Bao J, Abe H, Jaskowiak N. Diagnostic value of breast MRI in evaluating total extent of disease when non-calcified DCIS is present in stereotactic core biopsy samples [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-05.
Abstract P4-02-13: Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging breast MRI?
Authors: Benveniste APA , Ebuoma LO , Jonna A , Sam K , Severs FJ , Roark A , Sepulveda KA , Tamara O-P , Sedgwick EE
Published: February 2018

Purpose: Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging Breast MRI?

Materials and Methods: Retrospective review of women diagnosed with breast cancer who underwent a breast MRI for staging of disease was performed at a single institution from October 2012 to September 2015.

Results: Breast MRI for staging was done for 435 patients diagnosed with breast cancer. Ages ranging from 24 to 86 years old (median, 52 years); sizes ranging from 0.5 to 13.5 cm (mean, 3.5 cm). 29 patients (7 %) had biopsy-proven second tumors in the same breast but different quadrant as the primary tumor or in the contralateral breast. From the 435 patients, 304 had minimal/ mild BPE and 103 had moderate/marked BPE (28 missing). Of the patients with an invasive primary cancer and a second tumor in the same breast but different quadrant as the primary tumor or in the contralateral breast, 12 of 29 patients had discordance in subtypes between the primary and secondary tumors (41%) and 17 of 29 had concordance in the subtypes between the primary and secondary tumors (59%). 6.3% (19 out 304) of patients with minimal/ mild BPE had multicentric /bilateral disease and 9.7% (10 out 103) of patients with moderate/ marked BPE had multicentric/ bilateral breast cancer.

Conclusion: 435 patients with recent diagnosis of breast cancer who underwent staging breast MRI for diagnosis of additional sites of disease, 7% was diagnosed with an additional site of cancer. From these group of patients, approximately 6% had other site of disease among patients who had minimal/ mild BPE in the breast MRI versus 10% of patients with moderate/marked BPE. BPE may play a role in the setting of multicentric/ bilateral breast cancer.

Citation Format: Benveniste APA, Ebuoma LO, Jonna A, Sam K, Severs Jr. FJ, Roark A, Sepulveda KA, Tamara O-P, Sedgwick EE. Can background parenchymal enhancement (BPE) predict the chance of multicentric/ bilateral breast cancer on staging breast MRI? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-13.
Abstract P4-03-03: Not presented
Authors: Hurtado A , Wang S , Gilfillan S , Norum JH , Bergholtz H , Singh SK , Fosdahl AM , Nord S , Engebraten O , Lingjaerde OC , Bellet M , Sørlie T
Published: February 2018

This abstract was not presented at the symposium.
Abstract P4-03-14: OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling
Authors: Wu Z , Wang W , Zhang B , Xue J , Chi Y , Wu J
Published: February 2018

Triple-negative breast cancer (TNBC) or Basal-like breast cancer is characterized by worse prognosis than other breast cancer subtypes due to the rapid-arising therapeutic resistance accompanied by aggressive metastasis. The therapy-resistant tumor cells, including cancer stem-like cells (CSCs) with intrinsic resistance or tumor cells acquired resistance during treatments, could repopulate the primary tumors and serve as seeds for recurrent metastatic lesions. However, the molecular events orchestrating the innate and acquired therapeutic resistance are not completely understood. We found a recently identified linear ubiquitin-specific deubiquitinase OTULIN is overexpressed in breast tumors, especially in the basal-like subtype, compared with normal breast tissues. Moreover, OTULIN overexpression significantly increased TNBC cells resistance to chemotherapy and is associated with shorter RFS in breast cancer patients. Mechanistically, we found genotoxic treatments activate OTLULIN, which promotes epithelial-to-mesenchymal transition (EMT) in TNBC cells through increased activity of Wnt/β-Catenin signaling. OTULIN overexpression significantly increased TNBC cells resistance to chemodrugs while inhibiting Wnt/β-Catenin sensitized TNBC xenografts to Doxorubicin treatment in vivo. Our findings suggest that OTULIN-mediated Wnt/β-Catenin activation may increase TNBC therapeutic resistance and aggressiveness by promoting EMT. Targeting OTULIN and the chemotherapy-induced Wnt/β-Catenin activation may serves as promising strategy to mitigate drug resistance and reduce metastasis in TNBC patients receiving chemotherapy.

Citation Format: Wu Z, Wang W, Zhang B, Xue J, Chi Y, Wu J. OTULIN promotes resistance and metastasis upon chemotherapy in TNBC by activating Wnt/β-catenin signaling [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-03-14.
Abstract P4-04-04: Identification and development of oral estrogen receptor PROTAC degraders for breast cancer
Authors: Flanagan JJ , Qian Y , Gough SM , Andreoli M , Bookbinder M , Bradley J , Rousseau E , Willard R , Crews CM , Crew AP , Taylor I , Houston J
Published: February 2018

ER-positive breast cancers comprise approximately 70-80% of all newly diagnosed cases. Downregulation or degradation of ER is a treatment approach currently used in the clinic to target estrogen receptor signaling. Faslodex, the only clinically-approved ER-downregulator, is administered as a monthly intramuscular injection with limiting pharmaceutical properties. Reasoning that an orally-available estrogen receptor degrader would be beneficial to patients, we have leveraged our experience in targeted protein degradation to generate and characterize novel proteolysis targeting chimeras (PROTACs) against estrogen receptor alpha. PROTACs are heterobifunctional molecules that facilitate the formation of a “trimer complex” comprised of the PROTAC, a pathogenic target protein of interest and an E3 ligase, which catalyzes the ubiquitylation and subsequent degradation of the target protein via the proteasome. To identify novel ER degraders (ER PROTACs), we have used several in vitro assays to characterize the extent of target engagement and receptor degradation. Potent ER PROTACs with good oral exposure and other pharmaceutical properties in multiple pre-clinical species were further evaluated in breast cancer xenograft models. Orally-administered ER PROTACs achieved >80% degradation of estrogen receptor alpha and demonstrated single agent tumor growth inhibition in these disease models. Further, combination with a CDK4/6 inhibitor resulted in the expected improvement in anti-proliferative activity.

Citation Format: Flanagan JJ, Qian Y, Gough SM, Andreoli M, Bookbinder M, Bradley J, Rousseau E, Willard R, Crews CM, Crew AP, Taylor I, Houston J. Identification and development of oral estrogen receptor PROTAC degraders for breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-04.
Abstract P4-04-08: Therapeutic strategy for ERα mutation driven-endocrine resistance in ER-positive breast cancers
Authors: Kim J-A , Fuqua SAW
Published: February 2018

Background: Although estrogen receptor (ER)-positive breast cancers are treated with endocrine therapy, 25% of these patients are at risk of relapse and the development of acquired endocrine resistance. Recently mutations in the ER gene (ESR1) have been identified which induce resistance to endocrine therapy. The most frequent ESR1 mutation, Y537S, promotes ligand-independent ER activity. It is known that ER regulates the cell cycle in a ligand-dependent manner. In this study, we examined the effects of the Y537S ESR1 mutation on cell cycle signaling and therapeutic response to checkpoint inhibitor.

Material and Methods: MCF-7 cells expressing the Y537S ESR1 mutation were generated by CRISPR-Cas9 knock-in techniques. Cells were incubated in phenol red minus medium containing 5% charcoal-dextran treated serum for 5 days to remove exogenous hormones. Cell cycle and apoptosis were examined by Flow cytometry and Annexin-V assays. Proliferation was analyzed by BrdU incorporation. Cell senescence was determined using beta-galactosidase assays. Cell cycle checkpoint kinases were examined by western blot analysis. Cell growth was analyzed using soft agar or MTT assays.

Results: Levels of p53 and apoptosis pathway proteins were significantly elevated in Y537S ESR1 mutant cells using RNA expression and reverse-phase protein microarrays. The ATM/ATR and Chk1/Chk2 mediated checkpoint signaling, the upstream pathway of p53, was activated in ESR1 Y537S mutation, which was repressed with fulvestrant treatment. ESR1 Y537 mutant cells accumulated about 5 fold in S phase and 1.7 fold in G2/M phase compared to control cells in estrogen deprived (ED) condition. BrdU incorporation was also increased about 2.5 fold compared with parental cells in estrogen-free medium. In addition, ESR1 Y537 mutant cells expressed a DNA double-strand break marker, gamma-H2AX protein in ED condition. Apoptosis and senescence were observed in ESR1 Y537S mutant cells in regular medium, however, apoptosis was not shown in ED medium. Chk1 inhibitor, PF477736 sensitized MCF-7 expressing ESR1 Y537S mutation to endocrine treatments such as fulvestrant, tamoxifen and AZD9496.

Conclusion: Combination therapy with cell cycle checkpoint kinase inhibitor may lead better prognosis in ER mutation driven-endocrine resistance in postmenopausal breast cancers.

Citation Format: Kim J-A, Fuqua SAW. Therapeutic strategy for ERα mutation driven-endocrine resistance in ER-positive breast cancers [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-04-08.
Abstract P4-09-09: Correlation of breast cancer index (BCI) predictive (HoxB13/IL17BR) results to nodal status and hormone receptor expression in early stage HR+ breast cancer
Authors: Elias A , Israel MA , Zhang Y , Schnabel CA , Mayordomo J
Published: February 2018

Background: The HoxB13/IL17BR (H/I) ratio, the endocrine response component of the Breast Cancer Index (BCI), was initially discovered in patients with LN- breast cancer, and validated as a predictive biomarker of benefit from extended endocrine therapy (EET) in a cohort from MA.17 that included both LN- and LN+ patients. Here, correlative analyses were performed to further characterize BCI Predictive (H/I) results with nodal status and quantitative hormone receptor expression.

Methods: Analyses were performed using data from the BCI Clinical Database for Correlative Studies, an IRB-approved de-identified database that contains >50 clinicopathologic and molecular variables from cases submitted for BCI in clinical practice (N=19,126). Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of these cases. Cases from patients with confirmed nodal status were analyzed. Chi-squared tests and ANOVA were used to compare results between subgroups.

Results: Analyses included 13,114 patients (median age 58.9y; range 23-92y); 9562 were LN- and 3552 LN+. The distribution of individual H/I scores and proportion of patients classified as High H/I were generally similar in LN- and LN+ patients, though a modestly greater proportion of LN+ patients (46.2%) were classified as High H/I compared to LN- patients (42.0%; P<0.01). In both LN- and LN+ patients, median quantitative ER (qER) expression was slightly higher in patients with Low H/I than with High H/I; qPR showed the same trend but with a larger magnitude (P<0.0001 for both). Similar results were observed for percent positive staining by IHC (P<0.0001). In both LN- and LN+ patients, H/I showed a weak negative correlation with qER (LN-, 0.227; LN+, 0.192) and qPR expression (LN-, 0.311; LN+, 0.311).

Conclusion: In this study to evaluate potential biological correlates of BCI, results showed that H/I biomarker activity did not appear to be dependent on nodal status. Secondly, although ER expression is an established biomarker for endocrine sensitivity, High H/I status did not correlate with increased quantitative ER and PR expression. The H/I ratio may be an independent new marker for endocrine sensitivity independent of the strength of ER expression.

Citation Format: Elias A, Israel MA, Zhang Y, Schnabel CA, Mayordomo J. Correlation of breast cancer index (BCI) predictive (HoxB13/IL17BR) results to nodal status and hormone receptor expression in early stage HR+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-09.
Abstract P4-10-08: Withdrawn
Authors: Parekh A , Shen C , Asrari F , Alcorn S , Wright JL
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P4-10-11: An active approach to genetic counseling in Trinidadian women with breast cancer
Authors: George SH , Bravo GL , Sandoval AC , Palacio S , Ali J , Donenberg TR , Akbari MR , Narod S , Hurley J
Published: February 2018

Introduction

Breast cancer (BC) is the leading cause of cancer death in Caribbean women. The prevalence of deleterious mutations in BRCA1/2, PALB2 and RAD51C among unselected BC patients in the Caribbean is 5-25%. We previously reported data on low usage of genetic counseling services by Bahamian women. In order to improve the dissemination of genetic testing results to Caribbean probands and their families we developed a structured approach to genetic test result dissemination and family counseling.

Methods

After approval by the University of Miami IRB and the Ethics Committee of the Ministry of Health of Trinidad & Tobago, we prospectively evaluated the active approach to genetic counseling in 32 BC mutation carriers in Trinidad & Tobago in 2015. The intervention consisted of: 1) initial appointment with referring oncologist for results discussion; 2) review of family tree with proband to identify all relatives at 25% or 50% risk (ARR) who should attend the genetic counseling session; 3) preschedule a counseling appointment for ARR within 2 weeks; 4) written invitation to genetic counseling session; 5) handouts of genetic information given to proband to distribute to family members; 6) offer assistance with contacting family members; 7) free genetic testing to ARR who attended the family counseling session.

Results

Twenty-five carriers (78%) consented to enroll in the study. At initial counseling, probands identified 158 ARR, however full family pedigree review at post-result counseling/consultation identified 225 ARR. 101 ARR (64%) attended the information sessions and 76 participants (75.2%) consented to be tested for BC gene mutations. Genetic sequencing revealed 35 ARR (46%) were carriers of at least one mutation. The most frequent reasons for ARR not attending the meetings were: living abroad (18%), unable to be contacted (17%), refusing to participate (17%), not showing up (17%), probands being estranged from ARR (12%) or being afraid to know the results (7%).

Conclusions

In Trinidad & Tobago, a structured approach to the dissemination of genetic test results leads to a significant improvement in the rate of family participation compared to previous efforts (64% in Trinidad & Tobago vs. 9% in the Bahamas).

Citation Format: George SH, Bravo GL, Sandoval AC, Palacio S, Ali J, Donenberg TR, Akbari MR, Narod S, Hurley J. An active approach to genetic counseling in Trinidadian women with breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-11.
Abstract P4-13-04: Robotic nipple-sparing mastectomy with immediate prosthetic breast reconstruction : A preliminary study
Authors: Sarfati B , Struk S , Leymarie N , Honart JF , Rimareix F , Delaloge S , Saghatchian M , Ghouadni A , Alkhashnam H , Mazouni C , Kolb F
Published: February 2018

Background: Robotic nipple-sparing mastectomy (RNSM) could be a significant advancement in the treatment of selected breast cancers and prophylaxis. The aim of this prospective study was to assess feasibility of the RNSM with immediate prosthetic breast reconstruction (IPBR) on the first 50 consecutive cases performed in Gustave Roussy.

Methods: RNSM with IPBR was offered to patients with breast cup size A, B or C and ptosis grade ≤ 2. In case of oncologic surgery, RNSM was offered only if the patient fulfilled oncological indications for NSM (NAC). In case of prophylactic surgery, RNSM was offered only if a high-risk genetic mutation had been identified or if the patient was at high risk of breast cancer. The primary endpoint was the conversation rate to open technique. The duration of the surgery, the rate of postoperative complications, the length of the scar, the duration of drainage and hospital stay, the rate and duration of rehospitalization were also analyzed.

Results: Of 50 RNSM with IPBR from December 2015 to April 2017, 1 case of conversion to open technique occurred (2%) because of an uncontrolled bleeding from an internal mammary perforator. Two infections occurred (4%) : one led to implant loss. There were no cases of mastectomy skin flap or NAC necrosis. No other major complications were observed. The duration of the whole procedure was reduced gradually from 214 min to 86 min. Length of scar was between 2.5 and 5 cm. Patients were discharged home between the 4th and the 10th postoperative day after the removal of the drain.

Conclusion: Preliminary data attest to the feasibility, the reproducibility and the safety of this approach. However, long-term data are needed to confirm the reduced rate of skin and NAC necrosis compared to the open technique, the oncological safety and the aesthetic stability of the result.

Citation Format: Sarfati B, Struk S, Leymarie N, Honart JF, Rimareix F, Delaloge S, Saghatchian M, Ghouadni A, Alkhashnam H, Mazouni C, Kolb F. Robotic nipple-sparing mastectomy with immediate prosthetic breast reconstruction : A preliminary study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-04.
Abstract P4-13-05: Detection of local recurrence in premenopausal patients treated with neoadjuvant chemotherapy and mastectomy with or without breast reconstruction
Authors: Jacobson CE , Kozak M , Walck E , Hawley E , Horst K
Published: February 2018

Background: Women who undergo mastectomy for breast cancer treatment often undergo implant based or autologous reconstruction. There are limited data, however, as to whether reconstruction may interfere with detection of a locoregional recurrence. The goal of this study was to assess whether women who undergo reconstruction after mastectomy have an increased risk of local recurrence and/or longer time to local recurrence detection.

Methods: One hundred and fifty-four premenopausal patients who underwent neoadjuvant chemotherapy followed by mastectomy were identified between 2005 and 2015. Patients with de novo Stage IV disease or insufficient medical records were excluded from analysis. Patient and treatment variables were collected, including clinical stage, type of chemotherapy, type of surgery and reconstruction, use of postmastectomy radiotherapy, and use of endocrine therapy. Local recurrence (LR) was defined as a chest wall or skin recurrence. Regional failure (RF) was defined as recurrence in the axilla, supraclavicular fossa, or internal mammary nodes.

Results:

The median follow up for this cohort was 49.9 months. Of the 154 patients, 71 (46%) underwent unilateral mastectomy and 83 (54%) underwent bilateral mastectomies. Thirty patients (19%) elected to forgo reconstruction while 78 (51%) received tissue expander/implant based reconstruction, 29 (19%) received autologous reconstruction, and 17 (11%) had unknown reconstruction histories. Patients who had reconstruction had an increased time to detection of a LR compared to those without reconstruction (p=0.048). However, controlling for the T and N stage of disease, Cox regression demonstrated no observable difference in risk for LR between patients who underwent reconstruction compared to those who didn't. There was no difference in detection of RF between those with and without reconstruction (p=0.092).

Conclusions: Premenopausal patients treated with neoadjuvant chemotherapy followed by mastectomy with any type of reconstructive surgery had an increased time to local recurrence detection compared to those without reconstruction. There was no difference in the risk for local recurrence between those who underwent reconstruction compared to those who didn't.

Citation Format: Jacobson CE, Kozak M, Walck E, Hawley E, Horst K. Detection of local recurrence in premenopausal patients treated with neoadjuvant chemotherapy and mastectomy with or without breast reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-05.
Abstract P4-13-16: Impact of immediate breast reconstruction after mastectomy on the outcome of patients receiving neoadjuvant chemotherapy
Authors: Nogi H , Tomita S , Kamio M , Shioya H , Toriumi Y , Takeyama H
Published: February 2018

Background and purpose

In breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) is controversial. IBR might favor recurrences and metastases due to delayed adjuvant radiation therapy.

We retrospectively investigated whether IBR after mastectomy influenced the outcome of patients receiving neoadjuvant chemotherapy.

Patients and methods

Between 2006 and 2016, 243 breast cancer patients received total mastectomy after NAC, 48 of whom underwent IBR. Patients receiving IBR (IBR group) were compared to patients who did not receive IBR (no-IBR group) over a prolonged median follow-up time (72.3 moths).

The regimen was 4 cycles of epirubicin (100 or 75 mg/m2), 5-fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) followed by 4 cycles of docetaxel (75 mg/m2). Post-mastectomy radiation was applied in cases treated by IBR following the same selection criteria as for standard mastectomy regardless of the reconstruction approach.

Results

Patients in the IBR group were on average younger than patients in no-IBR

group (p<0.001). The percentage of patients with clinical T1/2 tumor was 81.2% in the IBR group and 58.4% in no-IBR group (p=0.0042). 2 patients (4.2%) in the IBR group and 9 patients (4.6%) in no-IBR group showed the locoregional recurrences. 2 patients (4.2%) in the IBR group and 20 patients (10.3%) showed distant metastases. There were no significant differences.

Conclusions

IBR after total mastectomy was not associated with worse rate of locoregional recurrences in patients receiving NAC.

Citation Format: Nogi H, Tomita S, Kamio M, Shioya H, Toriumi Y, Takeyama H. Impact of immediate breast reconstruction after mastectomy on the outcome of patients receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-13-16.
Abstract P5-01-02: Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results
Authors: Rauch GM , Adrada BE , Kappadath C , Candelaria RP , Huang ML , Santiago L , Moseley T , Scoggins ME , Knudtson JD , Lopez BP , Hess KR , Krishnamurthy S , Moulder S , Valero V , Yang W
Published: February 2018

Purpose: To report preliminary data in a pilot study evaluating the ability of Tc99m sestamibi Molecular Breast Imaging (MBI) to predict response and assess residual disease at the completion of neoadjuvant chemotherapy (NAC) in breast cancer patients.

Materials and Methods: Patients with localized, invasive breast cancer (T1-T4, N0-N3, M0) planned for NAC were enrolled in this prospective IRB approved clinical trial. All patients had digital mammography (DM), ultrasound (US), and MBI at baseline (T0), after 2 NAC cycles (T1), and at after NAC completion (T2). Tumor size and volume changes were compared with residual disease at surgery. MBI images were corrected for scatter and attenuation using a novel approach and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: tumor to background ratio (TBR), fractional activity uptake (FAU), and MBI-specific standardized uptake value (SUV). ROC analysis was performed.

Results: Patients (n=25) who completed NAC, had 75 imaging time points and had surgery, were included in this analysis. Median age was 49 years (range 31 -77). Eleven patients (11/25, 44%) had complete pathologic response (pCR). Absolute TBR values after 2 cycles (T1) and before surgery (T2) had highest correlation with pCR (AUC 0.81; 95% CI 0.63 to 0.99, p=0.01, and AUC 0.78; 95% CI 0.59 to 0.97, p=0.015, respectively). Change in SUV after 2 cycles, Δ SUV1 (T1-T0), (AUC 0.84; 95% CI 0.66 to 1.00, p=0.01) and change in SUV prior to surgery, Δ SUV2 (T2-T0) (AUC 0.80; 95% CI 0.60 to 1.00, p=0.02), were most predictive of pCR. Tumor size and volume showed modest specificity for detecting residual disease, and was highest for MBI (79%), followed by MMG (64%), and lowest for US (55%).

Conclusion: Quantitative MBI metrics show promise for the prediction of pCR in breast cancer patients undergoing NAC. Establishment of quantitative metrics for the early prediction of tumor response during NAC of breast cancer patients may provide an alternate to influencing NAC choice early in the management algorithm. Further investigation with a larger sample size is warranted.

Citation Format: Rauch GM, Adrada BE, Kappadath C, Candelaria RP, Huang ML, Santiago L, Moseley T, Scoggins ME, Knudtson JD, Lopez BP, Hess KR, Krishnamurthy S, Moulder S, Valero V, Yang W. Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-01-02.
Abstract P5-02-01: Predictive value of TILs in evaluation of 18F-FDG-PET in breast cancer
Authors: Hirakata T , Takaaki F , Kurozumi S , Katayama C , Yajima R , Obayashi S , Nakazawa Y , Tokuda N , Yanai K , Honda C , Kuwano H
Published: February 2018

Background:

Several recent clinical studies have evaluated the prognostic and predictive importance of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC). 18F-Fluorodeoxyglucose positron-emission (FDG-PET) CT was found to be effective for monitoring cancer cell viability of tissues and tumors, and it is used to evaluate the glucose metabolic rates of such tissues because most neoplasms have high glycolytic rates. FDG-uptake is also influenced by many factors, including inflammatory cells. In the present study, we investigated the relationship in evaluation of FDG-PET and degrees of TILs.

Patients and Methods:

Invasive carcinoma tissues of 100 breast cancer patients were examined. All patients underwent surgery. None of the patients had received preoperative chemotherapy. The proportional grades of stromal (Str)-TILs in surgical specimens were determined as follows: low (0-10%), intermediate (20-40%) and high (50-90%) grade, using the criteria of the International Working Group for TILs 2014 in breast cancer, using an immunohistochemical (IHC) method. The evaluation of PET was determined as follows, using standardized uptake value max (SUV max): low (<5) and high (>5). Estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, and nuclear glade were also measured by IHC.

Results:

Among the 100 patients, range of age was 36 to 86 (mean 58) years. Twenty-seven patients were pre-menopausal, seventy-one were postmenopausal, and two were unknown. Invasive ductal carcinoma was diagnosed in 97 (97%) of the patients, invasive lobular carcinoma was diagnosed in 2 (2%), and others was 1 (1%).We divided the cases into three groups based on the degrees of TILs, low (57%), Intermediate (33%) and high (10%). We divided the cases into three based on the degrees SUV max, low (78%) and high (22%). High TILs group significantly showed higher SUV max than that of lower SUV max group (P=0.009). High TILs group had statistically higher rates of ER negative (P=0.001), PgR negative (P=0.002), HER2 positive (P=0.007), and nuclear grade 3 (P=0.013) than those of low TILs group.

Conclusion:

The proportional grades of stromal (Str)-TILs were associated with the degrees of SUV max in primary breast tumor in FDG-PET. High FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. From our findings, the evaluation of TILs is to be useful for predicting a better prognosis or therapeutic effect in cases with high FDG-uptake which indicate higher risk of recurrent disease.

Citation Format: Hirakata T, Takaaki F, Kurozumi S, Katayama C, Yajima R, Obayashi S, Nakazawa Y, Tokuda N, Yanai K, Honda C, Kuwano H. Predictive value of TILs in evaluation of 18F-FDG-PET in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-02-01.
Abstract P5-03-06: Novel targets of breast cancer associated with inflammatory tumor microenvironment
Authors: Tiwari RK , Ben Rahoma G , Tuli N , Bednarczyk R , Maniyar RR , Chakraborty S , Singh S , Mittelman A , Geliebter J
Published: February 2018

Breast cancer affects one in eight women in the USA. Considerable progress in the identification of genetic lesions and their modulation has resulted in newer therapies making breast cancer a manageable disease. However, triple negative breast cancer is still difficult to treat and warrants a search for newer targets. To this end, we focused our attention towards the modulation of the breast cancer epithelium by other cell types such as the endothelial cells and the macrophages. The migratory macrophages and the estrogen sensitive migratory endothelial progenitor cells (EPCs) constitute the cellular milieu within the tumor microenvironment which continuously modulates breast cancer epithelium. We analyzed the interactions of the breast cancer cell lines (MCF-7 and MDA-MB-231) with the highly proliferative human umbilical cord derived CD133+/CD34+/VEGFR-2+ EPCs and M1 polarized macrophages (activated THP-1 cell line) in two separate in vitro studies. The readouts were cell proliferation, changes in epithelial to mesenchymal transition (EMT), and cellular differentiation. We observed morphological and cellular growth changes in the EPCs on treatment with conditioned medium (CM) generated from breast cancer cells, consistent with vasculogenesis and in vitro tubulogenesis. Both, MDA-MB-231 and MCF-7 CM, treatments resulted in enhanced EPCs proliferation and differentiation. However, the differentiation patterns were distinct, with MCF-7 CM increasing the number of cell clusters, whereas MDA-MB-231 CM increasing the number of adherent spindle shaped cells. The paracrine interaction was also assessed with M1 polarized macrophages. We observed decreased cell viability in MCF-7 and MDA-MB-231 cells following activated THP-1 CM and exosome treatments. Analysis of exosomes from activated THP-1 indicated an upregulation of 13 miRNAs compared to unactivated THP-1. The miRNA hsa-miR-146a-5p had the highest upregulation (44 fold increase). This specific miRNA has been observed in senescent cell and it inhibits cell proliferation, suggesting a possible mechanism for exosome-associated growth inhibition. The analysis of the paracrine interactive mediators between breast cancer cells, EPCs, and M1 polarized macrophages is likely to yield viable novel clinically translatable therapeutic targets.

Citation Format: Tiwari RK, Ben Rahoma G, Tuli N, Bednarczyk R, Maniyar RR, Chakraborty S, Singh S, Mittelman A, Geliebter J. Novel targets of breast cancer associated with inflammatory tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-03-06.
Abstract P5-07-10: Circulating microRNAs as early predictors of relapse in operable breast cancer
Authors: Agelaki S , Papadaki C , Stratigos M , Spiliotaki M , Markakis G , Mastrostamatis G , Mavroudis D , Ioannis S
Published: February 2018

Background: Metastasis remains a major threat for patients (pts) with operable breast cancer (BC). Recurrence could arise from a state of tumour dormancy during which there is growth restriction of undetectable micrometastases. The expression of dormancy and metastasis related miRNAs was evaluated in the plasma of pts with operable BC obtained before adjuvant therapy in order to discover novel biomarkers for the prediction of relapse.

Methods: Plasma miR-21, miR-23b, miR-190, miR-200b and miR-200c expression was assessed by qRT-PCR in 133 pts with early BC (non-relapsed, n=84; relapsed, n=49). Expression was classified as high or low according to the median values and was associated with pts' clinicopathological characteristics and clinical outcome.

Results: No correlation was observed between the expression of miRNAs and the clinicopathological characteristics of pts. After a median f-up of 90.5 mo, median Disease Free Interval (DFI) was significantly lower in pts with high compared to low miR-21 [105 mo vs not reached (NR); p=0.001], miR-200c (105.2 mo vs NR; p=0.007), or both miR-21 and miR-200c expression (81.37 mo vs NR; p=0.001). miR-21-high was also associated with decreased median Overall Survival (OS; p=0.041). In multivariate analysis the number of infiltrated axillary lymph nodes (N3 vs N0-N2, HR: 2.86; p= 0.004) and miR-21 expression (high vs low, HR: 2.824; p=0.001) were independent negative prognostic factors for DFI, whereas negative hormone receptor status (HR: 3.062; p=0.024) and miR-21 high (HR: 3.545; p=0.029) independently predicted for worse OS. Moreover, miR-21 expression was higher in pts presenting early relapse (defined as relapse at ≤ 3 yrs) compared to those without relapse at 5 yrs (p=0.032). Furthermore, higher miR-21 (p=0.038), miR-23b (p=0.039), miR-200b (p=0.027) and miR-200c (p<0.001) levels were observed in pts with late relapse (at ≥ 5 yrs) compared to those without relapse.

Conclusions: Differential expression levels of metastasis and/or dormancy related circulating miRNAs are encountered before adjuvant therapy in pts with operable BC presenting subsequent relapse compared to non-relapsed pts. In addition, circulating miRNAs could predict for early or late recurrence years before clinical detection of metastases. These results merit prospective validation in an independent pt cohort.

Citation Format: Agelaki S, Papadaki C, Stratigos M, Spiliotaki M, Markakis G, Mastrostamatis G, Mavroudis D, Ioannis S. Circulating microRNAs as early predictors of relapse in operable breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-10.
Abstract P5-09-01: Not presented
Authors: Vera YS , de la Rosa CG , Parra AC , Marchau LM , Saucedo EC , Camarillo CL
Published: February 2018

This abstract was not presented at the symposium.