bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES4-3: Regimens in HER2+ disease
Authors: Hurvitz SA 
Published: May 2016

Abstract
The discovery of the HER2 alteration and subsequent development of HER2-targeted therapy has substantially improved the natural history of HER2-positive metastatic breast cancer. In the past 17-years, four biologically targeted agents have been approved for the treatment of this disease subtype. These therapeutic advances have, in large part, been responsible for the significant improvement in median overall survival that can be expected now for a patient diagnosed with advanced HER2+ disease. While this progress has been remarkable, long-term durable remission is still rare, as the vast majority of patients will experience tumor progression with all available therapies. Thus the development of agents that prevent or circumvent mechanisms of resistance is still needed.

During this educational session, data relating to the use of trastuzumab, lapatinib, pertuzumab and trastuzumab emtansine will be explored in detail. Regimens involving chemotherapy, anti-hormonal treatment, and combinations of HER2-targeted agents will be evaluated. Specifically, questions surrounding optimal choice for first- and second-line therapy will be addressed by discussing the results of the CLEOPATRA, EMILIA and MARIANNE trials. The challenge of treating central nervous system metastases will be examined with a focus on promising agents under clinical investigation. In addition, differences in treatment response and disease outcome will be explored based on hormone receptor co-expression or activation of the PI3K pathway. As key evidence is discussed, the audience will be led through the decision-making process using case-based examples. Finally, innovative treatments undergoing clinical evaluation will be considered with a critical appraisal of preclinical and early clinical data.
It is expected that by the end of this session, audience members will possess an in-depth understanding of data relating to optimal treatment of HER2+ advanced disease and will be aware of promising avenues of research for continued areas of unmet need.
Citation Format: Hurvitz SA. Regimens in HER2+ disease. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES4-3.
Abstract ES8-2: Prognostic indicators in treatment of DCIS
Authors: Euhus DM 
Published: May 2016

Abstract
The goal of DCIS treatment is to avoid a future invasive breast cancer. Invasive breast cancer risk is heterogeneous across the population of DCIS patients. More than 40% of women with minimal, low grade DCIS will develop invasive breast cancer if left untreated and followed for more than 10 years. Risk of invasive recurrence is about 2% per year for DCIS treated by simple excision (lower for small low grade lesions and higher for larger high grade lesions). A reliable approach for risk-stratifying individual DCIS lesions could permit tailored approaches to therapy or avoidance of therapy all together in the lowest risk women. Screen-detected, grade 1 and 2 micropapillary DCIS in older women is likely the lowest risk lesion. Progression to invasive breast cancer is more likely related to focal myoepithelial cell dysfunction than molecular alterations in the bulk luminal cell populations. Nevertheless, p16, ER, COX2, HER-2/neu, and Ki67 staining patterns in the bulk luminal cell population have been linked to recurrence risk. A 12 gene recurrence score has been shown to predict the risk of recurrence for DCIS treated by excision without radiation. This assay was adapted from the 21-gene OncoTypeDx test and is weighted heavily towards proliferation markers. Accurate prediction of invasive recurrence risk will likely require detection of focal alterations in myopeithelial cells and the basement membrane.
Citation Format: Euhus DM. Prognostic indicators in treatment of DCIS. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES8-2.
Abstract MS1-2: Targeting CDK 4/6 in breast cancer
Authors: Finn R 
Published: May 2016

Abstract
For decades, cyclin-dependent kianses (CDKs) have been known to be critical regulators of cell cycle progression leading to the Nobel Prize in 2001 for their identification and characterization. Subsequently, alteration in these and associated proteins have been implicated in cancer. In breast cancer, they have been associated with various molecular subtypes, prognosis, and response to therapy. The concept of blocking CDKs has been around for some time but only recently have they seen clinical success. First generation CDK inhibitors did not demonstrate significant clinical activity and had unacceptable toxicity. In addition to having an appropriate compound, as with other molecular targeted agents, identification of a patient population most likely to benefit is critical to successful clinical development. Palbociclib (PD-0332991, Pfizer) is a first-in-class CDK 4/6 specific inhibitor. Pre-clinical studies identified that ER+ breast cancer models were most sensitive to growth inhibition with palbociclib and identified a synergistic interaction in inhibiting proliferation in combination with anti-estrogens (Finn et al 2009). These data served as a hypotheses for the Phase II Paloma-1/ TRIO 18 study of palbociclib +letrozole vs letrozole alone (Finn et al Lancet Oncolog 2015). Results of this study demonstrated a significant improvement in PFS with the combination and served as the basis for the expedited approval of palbociclib +letrozole as first line therapy for advanced post-menopausal ER+ breast cancer. Most common toxicities were neutropenia, leukopenia and fatigue. Subsequently, a consistent benefit was seen in combination with fulvestrant in more advanced settings (Turner et al NEJM 2015) with a similar toxicity profile. Currently there are several other CDK 4/6 inhibitors in development in breast cancer and other malignancies including abemaciclib (LY2835219, EliLilly) and ribociclib (LEE011, Novartis). In the presentation we will review the rationale for CDK 4/6 inhibition in breast cancer as well as clinical efficacy and toxicity data and the ongoing development of this new class of agent in breast cancer.
Citation Format: Finn R. Targeting CDK 4/6 in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr MS1-2.
Abstract OT1-03-02: Evaluation of the use of oral care to prevent oral mucositis in estrogen receptor positive metastatic breast cancer patients treated with everolimus: Phase III randomized control trial
Authors: Niikura N , Ohta Y , Hayashi N , Naito M , Kashiwabara K , Watanabe K , Yamashita T , Mukai H , Umeda M 
Published: May 2016

Abstract
Background:
In patients with estrogen receptor (ER)-positive advanced breast cancer, everolimus plus exemestane prolongs progression-free survival compared to exemestane monotherapy. However, as an adverse event from everolimus, oral mucositis (all grades) has been reported in 58% of all patients and 81% of Asian patients. Although no established prevention method is available, a previous study reported that professional oral care might prevent oral mucositis, and dentists have hypothesized that such care can reduce the occurrence of oral mucositis induced by everolimus. To evaluate this hypothesis, we compare the incidence of oral mucositis with and without professional oral care.
Method:
This is a randomized, multi-center, open-label, phase III study to evaluate the efficacy of professional oral care in preventing oral mucositis induced by everolimus in postmenopausal ER-positive metastatic breast cancer (MBC). Patients will be randomized into professional oral care and control groups (1:1 ratio). All patients will receive everolimus (10 mg daily) with exemestane (25 mg daily) and will continue everolimus until disease progression. Before the initiation of everolimus, instruction on a professional brushing method will be provided to both groups by specialists. In the professional oral care group, patients will receive teeth surface cleaning, scaling, and tongue cleaning before starting everolimus, and will continue to receive professional oral care weekly from oral surgeons throughout the 8 week treatment. In the control group, patients will brush their own teeth and gargle with 0.9% sodium chloride solution or water. The primary endpoint is the incidence of all grades of oral mucositis. The secondary endpoints are the incidence of over grade 2 and over 3 oral mucositis as determined by an oncologist and oral surgeons. The endpoints include onset and duration of oral mucositis. Major eligibility criteria include: 1) Postmenopausal women with ER positive MBC, and 2) No more than one prior chemotherapy treatment for MBC. Target accrual is 200 patients with a two-sided type I error rate of 5% and 80% power to detect 25% risk reduction. This study has just begun, and 5 of a planned 200 patients have been enrolled. (This study was registered with the UMIN 000016109).
Citation Format: Niikura N, Ohta Y, Hayashi N, Naito M, Kashiwabara K, Watanabe K, Yamashita T, Mukai H, Umeda M. Evaluation of the use of oral care to prevent oral mucositis in estrogen receptor positive metastatic breast cancer patients treated with everolimus: Phase III randomized control trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-02.
Abstract OT2-02-05: POSNOC: Positive sentinel node—Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy: A randomised trial looking at axillary treatment in early breast cancer
Authors: Goyal A 
Published: May 2016

Abstract
Background
Women with early breast cancer that has spread to 1 or 2 sentinel nodes (SNs) undergo axillary node clearance (ANC) or axillary radiotherapy (ART). The publication of the Z11 trial challenged this practice. There are however concerns about this trial which may limit the interpretation and generalisability of its results. These issues include the proportion of patients with micrometastases, variability in radiotherapy and applicability in patients undergoing mastectomy. Therefore further randomized trials are needed to define the role of axillary treatment in patients with 1 or 2 SNs with macrometastases. The UK-ANZ POSNOC trial is asking this question and will provide a more solid evidence base to inform clinical practice.
Methods
Trial design: A pragmatic, randomized, multicenter, non-inferiority trial.
Interventions: All participants will receive systemic adjuvant therapy according to local guidelines and radiotherapy to breast or chest wall if indicated. Women in the intervention group will receive systemic adjuvant therapy alone, whereas those receiving standard care will receive adjuvant therapy plus ANC or ART.
Study population: Women with unifocal or multifocal invasive breast cancer(≤5 cm) undergoing breast conserving surgery or mastectomy, who have 1 or 2 nodes with macrometastases at SN biopsy. The sample size is 1900 women. All participants will be followed up for 5 years.
Primary outcome: axillary recurrence at 5 years.
Secondary outcomes: arm morbidity, quality of life, anxiety, loco-regional recurrence, distant metastasis; time to axillary recurrence, axillary recurrence-free survival, disease-free and overall survival, contralateral breast cancer, non-breast malignancy and economic evaluation.
Key differences from Z11
a) stringent radiotherapy quality assurance program, b) prospective pathology reporting, b) axillary ultrasound is mandatory, b) mastectomy patients are eligible, c) axillary treatment in the standard group may be ANC or ART.
Current enrollment
126 patients.
Further information
Web - www.posnoc.co.uk
Email - posnoc@nottingham.ac.uk
Citation Format: Goyal A. POSNOC: Positive sentinel node—Adjuvant therapy alone versus adjuvant therapy plus clearance or axillary radiotherapy: A randomised trial looking at axillary treatment in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT2-02-05.
Abstract OT3-02-10: Nordic trip, a randomized phase 3 study in early triple negative breast cancer
Authors: Loman N , Linderholm B , Joensuu H , Ejlertsen B , Johannsson OT , Geisler J , Bendahl P-O , Ahlgren J , Lindman H 
Published: May 2016

Abstract
Background: Adjuvant treatment among the heterogeneous group of triple negative breast cancers (TNBC) is still a challenge. Recently published data indicate that platinum salts may have a role in the treatment of TNBC (v Minckwitz 2014), especially in BRCA-associated cases (Tutt 2014). Subgroup analyses from two large adjuvant studies indicate that also oral capecitabine may add a significant value in this subset of BC (Lindman 2010, O'Shaughnessy, 2010).
As a planned collaboration between the nordic countries, we are currently preparing a three-armed randomized phase 3 study of the addition of carboplatin and capecitabine respectively to a chemo backbone consisting of a taxane-antracycline based treatment in both the adjuvant and the neoadjuvant setting.
Objectives: The primary endpoint will be invasive disease-free survival (IDFS). Secondary endpoints will include IDFS in subsets of TNBC, eg according to gene-expression-based subtypes of TNBC(Lehmann 2011), and BRCA-mutation status. In the cohort treated neoadjuvant, biomarkers predicting pathological response will be identified with the purpose to validate them in the adjuvant cohort.
Method: 1800 patients (pts) with early TNBC stage 1 (&gt;10 mm) - 3 will be randomized 1:1:1 to three treatment arms.
A: nab-paclitaxel (nP) followed by epirubicine-cyclophosphamide (EC)
B: nP-capecitabine followed by EC-capecitabine.
C: nP-carboplatin followed by EC
Treatment will be given either in the adjuvant or in the neoadjuvant setting, the primary endpoint will include all randomized pts from both cohorts.
Statistical considerations: We assume a 75% five-year IDFS with standard treatment (A), and that a relative reduction of the event incidence of 30% for each of the two experimental treatments (B and C) would be a clinically relevant finding (HR=0.7). In order to achieve 80% power at a 0.05 significance level for each of the two comparisons A vs. B and A vs. C, 600 patients need to be evaluated in each of the three treatment arms. Stratification factors: pre- vs postoperative treatment, nodal status and treatment site.
Citation Format: Loman N, Linderholm B, Joensuu H, Ejlertsen B, Johannsson OT, Geisler J, Bendahl P-O, Ahlgren J, Lindman H. Nordic trip, a randomized phase 3 study in early triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-10.
Abstract P1-05-06: Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer
Authors: Bui QT , Kang KW 
Published: May 2016

Abstract
Epithelial-mesenchymal transition (EMT) is process in which epithelial cells undergo unique morphologic changes characterized by a transition from epithelial cobblestone phenotype to elongated fibroblastic phenotype (mesenchymal phenotype) leading to increased motility and invasion. Our previous study demonstrated that tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells showed the increased expression of mesenchymal marker proteins compared to the parent MCF-7 cells. Notch plays a crucial role in the promotion of EMT during both development and tumor progression. Especially, Notch-1 and Notch-4 were reported as prognostic markers in human breast cancer. Here, we found that the basal expression and activity of Notch-4 were significantly increased in TAMR-MCF-7 cells compared to control MCF-7 cells. Suppression of Notch-4 by either Notch inhibitors or Notch-4 siRNA significantly attenuated the EMT signaling. Interestingly, long-term treatment with DAPT, a Notch inhibitor, eventually led to partial reversal of EMT by up-regulating E-cadherin expression. Activated or tyrosine-phosphorylated STAT3 (pYSTAT3) protein is supposed as a critical signaling molecule in the regulation of tumorigenesis and metastasis of cancer cells. We further found that TAMR-MCF-7 cells exhibited constitutive STAT3 phosphorylation. Suppression of Notch-4 activation attenuated the activated STAT3 elevation in TAMR-MCF-7 cells. We hypothesized that Notch-4 regulated EMT in TAMR-MCF-7 cells via STAT3 signaling. Intrasplenic injection model of liver metastases was performed using TAMR-MCF-7 cells. Mice were received subcutaneous injections daily with DAPT (10 mg/kg) formed smaller tumor size in spleens and showed less micrometastatic tumor burden in livers compared to group treated with vehicle. In conclusion, inhibition of Notch signaling may have efficacy in the treatment of breast cancer metastasis.
Citation Format: Bui QT, Kang KW. Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-06.
Abstract P1-07-02: 5-year overall survival of early breast cancer during pregnancy: A multicenter French case control study
Authors: Vanlemmens L , Ploquin A , Delaloge S , Rouzier R , Lesur A , Frenel J-S , Loustalot C , Bachelot T , Provansal M , Ferrero J-M , Coussy F , Debled M , Kerbrat P , Vinceneux A , Djelila A , Baron M , Jebert S , Decoupigny E , Tresch E , Bonneterre J 
Published: May 2016

Abstract
Background: Breast cancer (BC) during pregnancy (BCP) is a rare situation that requires collaboration between oncologists, surgeons and obstetricians. The main objectives of this study were to compare the overall survival (OS) and disease free survival (DFS) of a multicenter cohort of pregnant patients (pts) with those of matched control pts.
Methods: Patients from 27 centers and diagnosed between 2000 and 2006 with histological confirmed M0 invasive BC were included in this retrospective study. For the cohort of BCP, pts whose pregnancy was interrupted were not eligible. Controls were matched to BCP pts on 5 criteria: clinical T (of TNM), hormonal receptor (HR) status, HER2 status, administration of neo-adjuvant chemotherapy and pathological nodal status in the absence of neo-adjuvant chemotherapy. Survival times were estimated from the date of diagnosis using Kaplan-Meier method. OS was calculated until death from every cause, DFS was calculated until relapse or death from every cause; patients alive were censored at the date of last news.
Results: 100 BCP pts were identified. Their clinical and pathological characteristics were described on a previous presentation (SABCS 2013 P6-06-07). Matched controls could not be found for 12 BCP pts. 88 BCP pts were matched with 204 controls. The only differences between the 2 populations in terms of characteristics or treatment were more radical mastectomy (p=0.036) and fewer taxane administrations in the BCP group (p=0.06). The median duration of follow-up was 8.2 years for cases and 7.7 years for controls. There were no differences between BCP pts and controls in 5-year OS: 83.4%, IC 95% (73.5-89.8) vs 83.8%, IC 95% (77.9-88.3) nor 7-year OS: 76.5% (65.5-84.4) vs 78.1% (71.5-83.3) (p=0.52). The 5-year DFS was 58.6% IC 95% (47.3-68.3) vs 67.2% IC 95% (60.2-73.2) (p= 0.16). However, 5-year DFS was lower in HR+ BCP pts subgroup than in HR+ control group (56.7% IC 95% (40.7-69.8) vs 70.9% IC 95% (61.4-78.5) (p=0.023).
Conclusion: This multicenter French large study confirmed that there are no differences on OS and DFS between pregnant and no pregnant pts, though this might not be true for HR subgroup.
Citation Format: Vanlemmens L, Ploquin A, Delaloge S, Rouzier R, Lesur A, Frenel J-S, Loustalot C, Bachelot T, Provansal M, Ferrero J-M, Coussy F, Debled M, Kerbrat P, Vinceneux A, Djelila A, Baron M, Jebert S, Decoupigny E, Tresch E, Bonneterre J. 5-year overall survival of early breast cancer during pregnancy: A multicenter French case control study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-02.
Abstract P1-07-03: Reproductive factors and subtype specific breast cancer risk
Authors: Anderson WF , Pfeiffer RM , Wohlfahrt J , Ejlertsen B , Jensen M-B , Kroman NT 
Published: May 2016

Abstract
Introduction: Reproductive history and breast cancer risk reportedly differ by the estrogen receptor (ER±) and by the joint expression of ER and the human epidermal growth factor-2 receptor (ER±/HER2±). However, large sample sizes are needed to identify risk factor associations for the relatively less common ER- subtypes.
Material and Methods: We, therefore, linked two large-scale and population-based Danish registries to assess the associations for parity, number of live births, and age at first live birth (AFLB) with receptor-specific breast cancer risk. Relative risks (RRs) and 95% confidence intervals (CIs) for associations were estimated with Poisson regression models.
Results: With nearly 31 million women-years of follow-up, there were 45786 Danish women between the ages 20-84 years who developed an invasive breast cancer during the study period 1992-2011. Parity significantly reduced risk for ER+ and ER+/HER2- subtypes (RR for ER+/HER2- = 0.92; 0.87, 0.98) and suggestively increased risk for ER- and ER-/HER2- subtypes (RR for ER-/HER2- = 1.16; 0.99, 1.36). RRs increased with advancing AFLB for ER+ cancers, especially among premenopausal women; and were elevated for ER- cancers among age groups 12-19 years and 30-34 years compared to the reference age group 20-24 years.
Conclusion: Associations of breast cancer risk and reproductive history varied among Danish women by ER± and by ER±/HER2±, consistent with receptor-specific etiological heterogeneity. Risk estimates for ER+ and ER+/HER2- cancers were similar to the well-established associations for breast cancer overall, whereas relative risks for ER- and ER/HER2- cancers tended to be null or the inverse of ER+ associations.
Citation Format: Anderson WF, Pfeiffer RM, Wohlfahrt J, Ejlertsen B, Jensen M-B, Kroman NT. Reproductive factors and subtype specific breast cancer risk. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-03.