bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-03-11: Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1
Authors: Liu Q , Zhu Y , Liu Y 
Published: March 2017

Abstract
Tamoxifen is the most widely used endocrine therapy in estrogen receptor (ER)- positive breast cancer patients. Tamoxifen resistance has been a major clinical problem and is accountable for relapse in about one third of these patients. Most of these recurrent patients will inevitably receive chemotherapy. However, the association between tamoxifen-resistance and chemosensitivity in breast cancer has never been explored. We found that both mRNA and protein expression of BARD1 and BRCA1 were significantly upregulated in tamoxifen-resistant MCF7 and T47D breast cancer cell lines, when compared with their parental lines. Furthermore, the tamoxifen-resistant cells were markedly more resistant to DNA-damaging chemotherapy including cisplatin and doxorubicin, but not to paclitaxel. Silencing BARD1 or BRCA1 by siRNAs or inhibition of BRCA1 phosphorylation by Dinaciclib restored the sensitivity to cisplatin and doxorubicin in tamoxifen-resistant cells. In addition, we identified that activated PI3K/AKT/ERK pathway in tamoxifen-resistant cells was responsible for the upregulation of BARD1 and BRCA1. BKM120, a PI3K inhibitor, decreased the expression of BARD1 and BRCA1 in tamoxifen-resistant cells and re-sensitized them to cisplatin and doxorubicin both in vitro and in xenografted mice. More importantly, higher BARD1 expression was significantly associated with poorer prognosis in breast cancer patients. BARD1 and BRCA1 were also significantly upregulated in recurrent breast cancer samples after tamoxifen compared with their primary counterparts. These results indicate an important role of BARD1 and BRCA1 in the chemoresistance of ER-positive breast cancer. Targeting PI3K/Akt pathway or BRCA1 phosphorylation may help to overcome the resistance to DNA-damaging chemotherapy in these tumors.
Citation Format: Liu Q, Zhu Y, Liu Y. Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-03-11.
Abstract P3-06-03: The short term effects of an AKT inhibitor (AZD5363) on biomarkers of the AKT pathway and anti-tumour activity in a breast cancer paired biopsy study (STAKT trial)
Authors: Roberston JFR , Cheung KL , Ahmed S , Coleman RE , Evans A , Holcombe C , Rea D , Rauchhaus P , Skene A , Littleford R , Jahan A , Kelly S , Lindermann JPO , Horgan K , Foxley A , Rugman P , Pass M 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P3-06-05: Receptor-mediated binding of HER2-targeted antibody-liposomal doxorubicin conjugate MM-302 increases liposome binding, nuclear doxorubicin, DNA damage and efficacy relative to untargeted PEGylated liposomal doxorubicin (PLD/Doxil)
Authors: Espelin C , Geretti E , Coma S , Koncki Z , Leonard S , Dumont N , Reynolds J , Molnar I , Wickham T 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P3-07-05: CDK8 inhibition improves the efficacy of ER- and HER2-targeted drugs in breast cancer
Authors: McDermott MS , Chumanevich A , Liang J , Chen M , Altilia S , Hennes C , Roninson IB , Broude EV 
Published: March 2017

Abstract
Over 70% of breast cancer patients are estrogen receptor (ER) positive and 25% of patients over-express HER2 making these patients susceptible to therapeutic intervention with ER- and HER2-targeted therapies, respectively. However, intrinsic and acquired resistance to targeted therapies is a significant clinical issue and new therapeutic approaches aimed to preventing and overcoming resistance are urgently needed. We have previously shown that high expression of CDK8, a transcription regulating kinase, is associated with shorter relapse free survival in both ER and HER2 positive breast cancer. We have found that CDK8 inhibition by a selective small molecule inhibitor (Senexin B), by shRNA knockdown or by CRISPR/CAS9 knockout, strongly inhibits estrogen signaling in ER-positive breast cancer cells. Senexin B produces a synergistic growth inhibitory effect with an antiestrogen fulvestrant in all the tested ER-positive breast cancer cell lines in vitro and in MCF7 xenograft model in vivo. Senexin B treatment also inhibited invasive growth of MCF7 xenografts. CDK8 inhibition suppressed the emergence of estrogen independence upon long-term estrogen deprivation. A highly synergistic growth inhibitory effect occurred when Senexin B was combined with an anti-HER2 monoclonal antibody (a biosimilar of trastuzumab) or with the HER2/EGFR small molecule inhibitor lapatinib. These synergistic effects were observed in all HER2 positive breast cancer cell lines tested including those that exhibit innate and acquired resistance to HER2 targeting therapy. Furthermore, combining lapatinib with Senexin B completely abrogated the emergence of acquired lapatinib resistance. Taken together these results suggest that CDK8 inhibition, when combined with either ER- or HER2-targeted therapies, offers a rational approach to improving the efficacy of targeted drugs in breast cancer.
Citation Format: McDermott MS, Chumanevich A, Liang J, Chen M, Altilia S, Hennes C, Roninson IB, Broude EV. CDK8 inhibition improves the efficacy of ER- and HER2-targeted drugs in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-05.
Abstract P3-07-14: Targeting ERR-α regulated lactate metabolism eliminates drug-resistant breast cancer cells
Authors: Quayle L , Park S , McDonnell DP , Ottewell PD , Holen I 
Published: March 2017

Abstract
Novel therapeutic strategies to eliminate chemo-resistant tumour cells responsible for the development of secondary lesions are essential in order to prevent breast cancer relapse. We have developed an in vitro model system enabling isolation of a putative metastasis-initiating breast cancer cell sub-population with a mitotically quiescent, drug-resistant phenotype. We hypothesise that this population is able to utilise oestrogen-related receptor-alpha (ERR-α)-regulated oxidative lactate metabolism and that inhibition of this critical survival pathway will result in elimination of tumour cells that have survived anti-cancer therapies.
Flow cytofluormetric monitoring of Vybrant® DiD retention identified a mitotically quiescent sub-population (~0.05%) in MDA-MB-231 human breast cancer cells grown under high glucose (11mM) conditions. DiD-retaining cells accumulated in the G2/M phase of the cell cycle and were shown to be non-senescent following cytochemical analysis of β-galactosidase activity. Cytotoxicity assays with doxorubicin (0.40μM for 72 hours) demonstrated increased survival in the quiescent fraction (40.76%) compared with the rapidly dividing bulk cell population (1.63%, P ≤ 0.0001). Isolated drug-resistant cells contained a sub-fraction (~1%) that was able to form new clonal populations following cessation of treatment. Mitotically quiescent cells were cultured under high glucose (11mM) or glucose-depleted conditions with high lactate (22mM) in the presence of ERR-α inhibitors Cpd29 (10μM) or XCT790 (10μM). Colony formation was completely eliminated in Cpd29- and XCT790-treated samples compared to untreated controls. Drug-resistant sub-clones were isolated from the quiescent population following 72 hours treatment with doxorubicin (0.40μM) and were cultured under glucose-depleted conditions with high lactate (22mM) in the presence of ERR-α inhibitors Cpd29 (10μM) or XCT790 (10μM). In both instances, colony formation was completely prevented.
We provide the first evidence that blocking cellular energy production through inhibition of ERR-α regulated oxidative lactate metabolism can eradicate a chemo-resistant, quiescent breast cancer cell population. Our data suggest that ERR-α inhibitors may be used in combination with chemotherapy to eliminate minimal residual disease and reduce breast cancer recurrence.
Citation Format: Quayle L, Park S, McDonnell DP, Ottewell PD, Holen I. Targeting ERR-α regulated lactate metabolism eliminates drug-resistant breast cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-14.
Abstract P3-08-08: Preferences for breast cancer risk reduction among BRCA1 and BRCA2 mutation carriers: A discrete choice experiment
Authors: Liede A , Evans G , Metcalfe KA , Price M , Snyder C , Lynch HT , Friedman S , Amelio J , Posner J , Lindeman G , Mansfield CA 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P3-13-16: 200 experiences of oncoplastic surgery with the omental flap reconstruction
Authors: Abe N , Sagawa N , Unesoko M , Zaha H 
Published: March 2017

Abstract
Background:There are several small case series about the omental flap for breast reconstructions. However, the long-term oncological safety and the clinical benefits remain uncertain, especially the flap is used as a part of oncoplastic breast surgery. We retrospectively studied 200 patients who underwent oncoplastic breast surgery using the laparoscopically harvested omental flap.
Methods:A retrospective chart review of 200 patients who underwent oncoplastic surgery using the omental flap at our institution from April 2002 to March 2016 was performed. All the omental flaps were laparoscopically harvested, and mainly used as a partial reconstruction immediate after breast-conserving surgery (BCS). Short- and long-term laparoscopy-associated complications, local recurrences and cosmetic outcomes were evaluated.
Results:Although 46 cases of nipple-sparing mastectomy or skin-sparing mastectomy were included, most of patients underwent partial breast reconstruction after BCS. The successful rate of laparoscopically harvesting of the omental flap was 99.5% (199 out of 200). The rate of complications was 12.0%. Laparoscopy-associated complications occurred in 4 cases (2.0%). The rate of positive margin was 6.5%. Local recurrence occurred in two cases (1.0%) during medial follow-up period of 78 months. In 24 patients (12.0%), the volume of the flap was insufficient. When applied to nipple-sparing mastectomy or skin-sparing mastectomy, volume luck occurred in 32.6% of patients. Cosmetic outcome was mostly satisfactory. Approximately 80% of patients scored good or excellent evaluated with 4 point scale by 3 health professions. The size of the reconstructed breast basically did not change even after radiation therapy. Donor-site scars were almost negligible just like those of laparoscopic cholecystectomy.
Conclusions:The laparoscopically harvested omental flap has minimal donor-site morbidity and deformity. The long-term oncological safety is also promising. Although there is a limit of adaptable volume, the omental flap is an attractive option in partial breast reconstruction after BCS.
Citation Format: Abe N, Sagawa N, Unesoko M, Zaha H. 200 experiences of oncoplastic surgery with the omental flap reconstruction [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-16.
Abstract P3-13-28: Lipofilling of the axilla to reduce secondary lymphedema after axillary lymph node dissection
Authors: Vandermeeren L , Belgrado J-P , Vankerckhove S , Valsamis J-B , Feipel V , Rooze M , Moraine J-J , Hertens D , Carly B , Liebens F 
Published: March 2017

Abstract
This abstract was not presented at the symposium.
Abstract P3-14-03: Does fat transfer increase the risk of breast cancer recurrence? A meta-analysis involving 2382 patients
Authors: Wazir U , Chehade HEH , Headon H , Oteifa M , Kasem A , Mokbel K 
Published: March 2017

Abstract
Introduction: Lipofilling is an increasingly popular technique for breast reconstruction following both mastectomy and breast conserving surgery. However, concerns remain over its oncological safety and its effect on cancer recurrence.
Methods: A systematic literature review and meta-analysis was carried out. Patients who had undergone mastectomy and patients who had undergone breast conserving surgery (BCS) were looked at separately in order to investigate whether the addition of lipofilling had a significant effect on locoregional recurrence rate.
Results: Eleven studies were used in the analysis yielding a total of 2382 patients. For patients undergoing mastectomy (mean follow up = 36.2 months: range=12-90) or BCS (mean follow up = 30.2 months: range = 12-60) , the addition of lipofilling was not found to significantly affect the locoregional recurrence rate.
Conclusion: This meta-nalysis demonstrates that lipofilling is an oncologically safe procedure to be incorporated into breast reconstruction following either mastectomy or BCS for breast cancer. However a careful oncological follow up is recommended. In the future, more adequately- powered controlled clinical trials are needed in order to fully understand long term outcomes after lipofilling.
Citation Format: Wazir U, Chehade HEH, Headon H, Oteifa M, Kasem A, Mokbel K. Does fat transfer increase the risk of breast cancer recurrence? A meta-analysis involving 2382 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-03.
Abstract P3-14-08: Immediate breast reconstruction is highly accepted by breast cancer patients undergoing mastectomy when routinely offered- Recent experience of an Australian tertiary oncoplastic breast unit
Authors: Cheung DSM , Trinh L , Edirimanne S , Eslick G 
Published: March 2017

Abstract
Introduction:
Despite recommendations by breast cancer guidelines, that immediate breast reconstruction (IBR) should be offered to all breast cancer patients considered for mastectomy national IBR rates have been reported as low as 12% in Australia. We report our oncoplastic breast cancer unit experience on acceptance of IBR, where it is routinely offered for all the medical fit breast cancer patients.
Methods:
We retrospectively reviewed, prospectively collected data on IBR by 3 oncoplastic breast cancer surgeons from 1st of September 2014 to 31st of March 2016.Patients were considered to be unfit for IBR if they were American Society of Anasthesiologist (ASA) Score 4 or 5, have unstable psychiatric illness, inflammatory breast cancer or high metastatic cancer burden. All the patients who were fit for IBR were offered both prosthetic and autologous IBR options.
Results:
137 patients underwent mastectomy operation, of whom 27 were considered unfit for IBR. Of the remaining 110 patients, 84 (76%) accepted IBR. Of the patients who had IBR 64 (76%) had single stage prosthetic, 15 (18%) two stage prosthetic and 5 (6%) autologous reconstructions. Those who accepted IBR were younger compared to those who didn't have IBR (median age: 47 yrs vs. 67 yrs, p&lt;0.001), and were more likely to be in current relationship (78.57% vs. 61.54%, p=0.06). All the three surgeons had high IBR acceptance rates (70.45%, 71.43%, 84.44%) and patient insurance status did not influence IBR acceptance rate (public 57% vs. private 65%, p=0.47). The majority of patients (25 of 26) who did not accept IBR stated that breast reconstruction was not important for their body image.
Conclusion:
Our recent data shows, in Australia, when routinely offered to breast cancer patients who are fit for reconstructive surgery by oncoplastic breast cancer surgeons, IBR is highly accepted. Younger patients and those who are in current relationship, were more likely to accept IBR, whereas, individual perception of insignificance of breast reconstruction for the body image was the main determinant of not accepting IBR.
Citation Format: Cheung DSM, Trinh L, Edirimanne S, Eslick G. Immediate breast reconstruction is highly accepted by breast cancer patients undergoing mastectomy when routinely offered- Recent experience of an Australian tertiary oncoplastic breast unit [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-08.
Abstract P3-14-13: Total mastectomy and immediate breast reconstruction for breast cancer: A ten-year Canadian single institution experience
Authors: Younan RJ , Al Khaldi M , Maalouf C , Guez M , Boulva K , robidoux A , Nassif E , Poljicak M , BouMerhi J , Bernier C , Patocskai E 
Published: March 2017

Abstract
Fear of high local recurrence rate associated with immediate breast reconstruction (IBR) following total mastectomy for breast cancer might be a contributing factor to the low rate of immediate reconstruction performed in Quebec. The aim of this study was to demonstrate the oncological safety of total mastectomy with immediate breast reconstruction.
A retrospective chart review of all patients who underwent total mastectomy with immediate breast reconstruction at the University of Montreal Hospital Center between 2006 and 2015 was performed.
375 patients (420 cases) met the inclusion criteria. The mean age was 51.5 years (25-77). The median follow-up was 45.6 months (0.4-115.2). Clinical cancer staging was done according to the American Joint Committee on Cancer (AJCC) criteria. 349 cases (83.1%) were classified as Stage &lt; cIIb and 71 cases (16.9%) as ≥ cIIb. 73 patients (19.5%) received neoadjuvant chemotherapy, 113 (30.1%) received adjuvant chemotherapy and 91 (21.7%) received postoperative radiotherapy. Only 4 patients (3.5%) had a significant delay in receiving adjuvant chemotherapy and 4 patients (4.4%) had a delay in initiation of radiotherapy. In total, there were 12 (2.6%) local recurrences and 29 (7.7%) distant recurrences.
The results of this study demonstrate a low rate of local recurrence that is comparable to the current litterature. Total mastectomy in association with immediate breast reconstruction is therefore an oncologically safe approach for the treatment of breast cancer and should be more widely adopted by medical centers throughout Quebec.
Citation Format: Younan RJ, Al Khaldi M, Maalouf C, Guez M, Boulva K, robidoux A, Nassif E, Poljicak M, BouMerhi J, Bernier C, Patocskai E. Total mastectomy and immediate breast reconstruction for breast cancer: A ten-year Canadian single institution experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-14-13.
Abstract P3-17-03: DCIS and the risk of breast cancer death - A case control study
Authors: Wadsten C , Garmo H , Fredriksson I , Sund M , Wärnberg F 
Published: March 2017

Abstract
Introduction
The risk of breast cancer death after a primary ductal carcinoma in situ (DCIS) is less than 2 % after 10 years. Whereas in situ recurrences do not influence survival, a 17-fold elevated risk of breast cancer specific mortality has been shown for invasive recurrences. Adjuvant radiotherapy (RT) effectively reduces recurrences after breast conserving surgery (BCS) for DCIS, but no studies have been able to demonstrate a survival benefit from adjuvant RT treatment or from choosing mastectomy instead of BCS. Here patient and tumour related risk factors for breast cancer death in women with a pure primary DCIS were studied.
Patients and methods
Women registered with a primary DCIS, between 1992-2012 in three of Sweden´s health care regions with a population of approximately 5.2 million, were enrolled in a nested case-control study. Out of 6,964 women with DCIS, 96 patients who later died from breast cancer were identified. Four controls per case (n=318) were randomly selected by incidence density sampling. We retrieved medical records and pathology reports and calculated OR with 95% CIs for various variables using conditional logistic regression.
Results
Of the 96 cases, 10 patients developed distant metastasis without a known local recurrence. In 56 patients death was preceded by an invasive ipsilateral recurrence and in 3 patients by a recurrent ipsilateral DCIS. Seven patients had invasive breast events in both the ipsilateral and the contralateral breast. Seventeen patients had contralateral invasive breast cancer and 3 patients contralateral DCIS.
Multifocality and tumour size over 25mm (OR 2.6 (1.6 to 4.2)), positive or uncertain margin status (OR 2.8 (1.6 to 4.9)) and detection outside screening (OR 2.1 (1.2 to 3.9)) increased the risk of breast cancer death in univariate analysis, when adjusted for age and year of diagnosis. Suspicion of micro-invasion and nuclear grade 3 was associated with a nonsignificant increased risk, OR 1.8 (0.6 to 5.0) and 2.6 (0.9-6.5), respectively. The risk was not affected by age or treatment. Tumour size and margin status remained significant in the multivariable analysis, when adjusted for treatment and for contralateral breast cancer (OR 2.0 (1.2 to 3.7)).
Conclusion
In the present study, large tumours and positive or uncertain margin status were significant risk factors for later breast cancer death after a primary DCIS. More extensive treatment was not related to a lower risk. The significance of tumour biology and nuclear grade will be further examined and evaluated.
Citation Format: Wadsten C, Garmo H, Fredriksson I, Sund M, Wärnberg F. DCIS and the risk of breast cancer death - A case control study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-03.
Abstract P3-17-08: The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ. An updated meta-analysis involving 9803 patients
Authors: Chehade HEH , Headon H , Wazir U , El Tokhy O , Kasem A , Mokbel K 
Published: March 2017

Abstract
Background: Ductal carcinoma in situ (DCIS) is the predominant pre-invasive neoplasia of the breast. It was observed that omission of axillary dissection in those with pure DCIS had no adverse effect on survival or recurrence. Therefore, axillary dissection typically does not feature in the management of DCIS. However, it has recently been purported that in some cases of DCIS, the axillary lymph nodes may show evidence of invasive disease. Consequently, there may be a role for sentinel lymph node biopsy (SLNB) in patients with DCIS with a high risk of invasion.
Materials and Methods: Systematic literature review identified 48 studies (9803 DCIS patients who underwent SLNB). Separate analyses for patients diagnosed preoperatively by core sampling and patients diagnosed postoperatively by specimen pathology were conducted to determine the percentage of patients with axillary nodal involvement. Patient factors were analysed for associations with risk of nodal involvement.
Results: The mean percentage of positive SLNBs was higher in the pre-operative group (5.95% vs. 3.02%; p=0.0201). Meta-regression analysis showed a direct association with tumour size (p=0.0333) and grade(p=0.00839), but not median age nor tumour upstage rate.
Conclusions: SLNB should be considered in patients with a pre-operative diagnosis of extensive and/or high-grade DCIS after a careful multidisciplinary discussion in order to identify those patients who have unrecognised axillary spread.
Citation Format: Chehade HEH, Headon H, Wazir U, El Tokhy O, Kasem A, Mokbel K. The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ. An updated meta-analysis involving 9803 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-08.