GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (15)
  • 1
    Online Resource
    Online Resource
    New Strategies in Breast Cancer: The Significance of Molecular Subtypes in Systemic Adjuvant Treatment for Small T1a,bN0M0 Tumors
    American Association for Cancer Research (AACR) ; 2014
    In:  Clinical Cancer Research Vol. 20, No. 24 ( 2014-12-15), p. 6242-6246
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 20, No. 24 ( 2014-12-15), p. 6242-6246
    Abstract: Awareness of breast cancer heterogeneity has strikingly increased in the past decade in parallel with the development of high-throughput molecular tests. Beyond the clear usefulness of antiestrogen treatment in luminal tumors and trastuzumab in HER2-positive tumors, breast cancer subtypes may have additional clinical and predictive roles that can be relevant to clinical practice. In this article, we discuss the significance of molecular subtypes in the systemic treatment of early-stage breast tumors smaller than 1 cm (T1a,bN0M0) and suggest new strategies for future treatment recommendations for these patients. Clin Cancer Res; 20(24); 6242–6. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-14-1086
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract PD5-06: Safety of assisted reproductive technologies (ART) following treatment completion in young women with germline BRCA pathogenic variants having a pregnancy after breast cancer
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD5-06-PD5-06
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD5-06-PD5-06
    Abstract: BACKGROUND: Young breast cancer (BC) survivors are at risk of infertility. Ovarian stimulation for fertility preservation before (neo)adjuvant chemotherapy is standard of care. Research efforts have shown no negative prognostic effect of pregnancy following BC therapy, also among BRCA carriers. Currently, poor evidence is available on the safety to undergo ART following BC treatment, with no data in carriers of germline BRCA pathogenic variants. To provide evidence on the safety of fertility treatments in this specific population, we assessed the outcomes of a cohort of BRCA-mutated BC survivors who had a pregnancy after prior BC history by comparing the group of patients who underwent ART to achieve pregnancy to the group with spontaneous pregnancy. METHODS: We conducted a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤ 40 years with stage I-III BC, between January 2000 and December 2012, bearing germline BRCA1/2 pathogenic variants. Survivors with a pregnancy (any outcome) after BC, with no disease-free survival (DFS) event before pregnancy, were assigned to the ART and non-ART group if their pregnancy was achieved through ART or spontaneously, respectively. ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), and embryo transfer under hormonal replacement therapy (HRT). RESULTS: Of 1,424 patients registered in the study, 168 with a pregnancy after BC were included in the present analysis. A total of 22 patients were included in the ART group and 146 in the non-ART group. Before BC diagnosis, 18.2% patients in the ART group had at least one child, compared to 38.4% in the non-ART group (P=0.030). Patients had a median age at BC diagnosis of 33.0 vs 30.2 years old in the ART group and in the non-ART group, respectively (P=0.004); 45.4% and 17.1% had grade 1-2 tumors, respectively (P=0.008), and 59.1% vs 31.5% had hormone receptor-positive tumors, respectively (P=0.016). Both cohorts had similar tumor size and nodal stage characteristics. Type and duration of endocrine therapy were comparable between groups. The type of ART was not specified in 5 survivors (22.7%). Ovulation induction was used in 1 patient (4.5%), ovarian stimulation in 7 patients (31.8%), embryo transfer under HRT following oocyte donation in 5 patients (22.7%), and embryo transfer under HRT following oocyte and/or embryo cryopreservation for fertility preservation in 4 patients (18.2%). Median age at conception among survivors was 39.7 years in the ART group versus 35.4 years in the non-ART group (P & lt;0.001). Overall, no differences in obstetrical outcomes were observed between groups, although there were more delivery complications in the ART group vs the non-ART group (22.1% vs 4.1%, respectively, P=0.011). Median follow-up from pregnancy was 3.4 years (range: 0.8-8.6) for patients in the ART group vs 5.0 years (range: 0.8-17.6) in the non-ART group (P=0.009). In the ART group, 2 patients (9.1%) experienced a DFS event (both were loco-regional recurrences) as compared to 40 patients (27.4%) in the non-ART group (P=0.182). No patients died in the ART group compared to 10 patients (6.9%) in the non-ART group. CONCLUSIONS: To our knowledge, this is the first study assessing the safety of ART in BC survivors bearing germline BRCA pathogenic variants. Even though the exposed cohort was small, results showed that the use of ART does not appear to increase the relapse risk at short-term follow-up. Further reproductive studies in BRCA-mutated BC patients are warranted. Citation Format: Margherita Condorelli, Marco Bruzzone, Marcello Ceppi, Alberta Ferrari, Albert Grinshpun, Anne-Sophie Hamy, Evandro de Azambuja, Estela Carrasco, Fedro A. Peccatori, Antonio Di Meglio, Shani Paluch-Shimon, Philip D. Poorvu, Marta Venturelli, Christine Rousset-Jablonski, Claire Senechal, Luca Livraghi, Riccardo Ponzone, Laura De Marchis, Katarzyna Pogoda, Amir Sonnenblick, Cynthia Villarreal-Garza, Octavi Córdoba, Luis Teixeira, Florian Clatot, Kevin Punie, Rossella Graffeo Galbiati, Maria Vittoria Dieci, Alejandro Pérez-Fidalgo, Francois P. Duhoux, Fabio Puglisi, Arlindo R. Ferreira, Eva Blondeaux, Tamar Peretz-Yablonski, Olivier Caron, Claire Saule, Lieveke Ameye, Judith Balmaña, Ann H. Partridge, Hatem A. Azim, Jr, Isabelle Demeestere, Matteo Lambertini. Safety of assisted reproductive technologies (ART) following treatment completion in young women with germline BRCA pathogenic variants having a pregnancy after breast cancer [abstract] . In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-PD5-06
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Abstract P5-13-19: Sarcopenia and skeletal muscle density as predictors of toxicity in patients with metastatic breast cancer receiving alpelisib
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-13-19-P5-13-19
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P5-13-19-P5-13-19
    Abstract: Background: Poor body composition metrics (BCM) are associated with inferior cancer outcomes. Alpelisib, a PIK3CA inhibitor, is increasingly used in approximately 40% of hormone receptor positive HER2 negative (luminal) metastatic breast (HR-MBC) patients who carry a somatic mutation in the PIK3CA gene. In the SOLAR-1, the clinical trial that led to FDA approval, serious adverse reactions occurred in 35% patients who were treated with Alpelisib and severe hyperglycemia was reported in 65% of the patients. Alpelisib is given at a fixed dose (300 mg daily) regardless of variables such as high adiposity or low muscle mass also called sarcopenia. In this study we investigated the association of BCM with toxicity and response to Alpelisib. Methods: Eligible HR-MBC patients treated with Alpelisib at Tel Aviv Sourasky Medical Center were identified. Toxicity grading, dose reduction, treatment discontinuation and hospitalizations were recorded. Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and skeletal muscle density (SMD) were measured at the third lumbar (L3) vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) & lt;41 (Martin, JCO 2012). Low skeletal muscle density (SMD) was defined as & lt; 37.8 Hounsfield Units (HU). Fisher exact tests, t tests, the Kaplan-Meier method, and Cox regression modeling were used. Results: All together Seventeen HR-MBC with PIK3CA mutation treated with Alpelisib met the study requirements. Median age was 63 (range 37-82). Of them 71% were sarcopenic. Any grade toxicity appeared in 83% of the sarcopenic patients versus 20% is the non-sarcopenic (P=0.0276). Both toxicity-related hospitalization and grade 3-4 toxicities and were found in 25% of the sarcopenic vs 0% in the non-sarcopenic. Severe adverse events - defined as grade 3-4 toxicities, hospitalization and dose reductions appeared in 66.6% of the sarcopenic vs 40% of the non-sarcopenic (P=NS). Low SMD appeared in 76% of the cohort. In the low SMD group 69% experienced grade 3-4 toxicity vs 25% in high SMD (P=NS). Hyperglycemia in all grades appeared in all the sarcopenic patients and 80% of the non-sarcopenic. Time to treatment failure (time to progression or toxicity) was numerically shorter in the sarcopenic group vs non-sarcopenic group (82 days vs 114 days respectively). Conclusion: AEs percentage was significantly higher in patients with sarcopenia. These AEs were seen more often in the early cycles. TTF on Alpelisib was shorter in the sarcopenic and low SMD groups. We assume that it was not statistically significant probably due to the low number of patients. Hence, we suggest a novel tool including two parameters (sarcopenia and SMD) for prediction of treatment toxicity which may serve for better treatment decision in the course of the disease in HR-MBC. As Aplelisib is reimbursed in Israel since 2021, we expect additional patients in our cohort and at SABCS 2021, we will extend our cohort and analysis. Data and statisticsSarcopenicNon-SarcopenicP-valueLow SMDHigh SMDP-valueHyperglicemia all grades100%80%0.294192.31%100%0.0475Hyperglicemia grade 3-433.33%40%138.46%25%1AEs all grades83.33%20%0.027669.23%50%0.584AEs grade 3-425%00.514715.38%25%1SAE including G3-4 AEs + hospitalization + dose reductions66.67%40%0.592869.23%25%0.25TTF (days)82114187991 Citation Format: Ari Raphael, Rivka Kessner, Rebeka Raphael, Amir Sonnenblick, Shlomit Strulov Shachar. Sarcopenia and skeletal muscle density as predictors of toxicity in patients with metastatic breast cancer receiving alpelisib [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-19.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P5-13-19
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract PD10-04: Phase Ib/II open-label, randomized trial of atezolizumab (atezo) with ipatasertib (ipat) and fulvestrant (fulv) vs control in MORPHEUS-HR+ breast cancer (M-HR+ BC) and atezo with ipat vs control in MORPHEUS triple negative breast cancer (M-TNBC)
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD10-04-PD10-04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD10-04-PD10-04
    Abstract: Background: The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to gauge safety and identify early efficacy signals in treatment (tx) combinations across cancers. Within MORPHEUS, atezo (anti-PD-L1) was evaluated with ipat, an oral AKT inhibitor, with (M-HR+ BC) and without (M-TNBC) fulv. Methods: In 2 separate randomized trials, eligible immune checkpoint inhibitor naive pts with either 2L/3L HR+ chemotherapy-naive BC who had prior CDK4/6 inhibitor treatment or 2L TNBC, received atezo (840 mg D1, 15) with ipat (400 mg D1-21); pts with HR+ BC also received fulv monthly. Control tx for M-HR+ BC (NCT03280563) was fulv and for M-TNBC (NCT03424005) was capecitabine; given the adaptive nature of the MORPHEUS platform only some of the control arm pts were enrolled concurrently with pts in the ipat arms for M-HR+ BC. Primary endpoints were ORR (overall response rate; investigator-assessed RECIST 1.1) and safety. Progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Results: Median duration of survival follow-up was 7.6 months for M-HR+ BC (data cutoff: Aug 2020) and 10.8 for M-TNBC (data cutoff: Mar 2021). In M-HR+ BC, none of whom received prior fulvestrant, 26 pts received atezo + ipat + fulv and 15 received fulv. Confirmed ORRs were 23.1% (95% CI: 9.0, 43.7) and 0% (95% CI: 0, 21.8), respectively. Median PFS was 4.4 mo (95% CI: 1.6, not evaluable) and 1.9 mo (95% CI: 1.6, 3.9), respectively. Updated survival data will be presented. Respectively, 61.5% and 20.0% of pts had Gr 3-4 AEs; no G5 AEs were observed; serious AEs (SAEs) occurred in 38.5% and 13.3% of pts; 7.7% and 0% of pts had tx-related AEs leading to tx withdrawal. The most common tx-related AEs were rash (73.0%), diarrhea (53.8%), nausea (42.3%), fatigue (26.9%), vomiting (23.1%), decreased appetite (19.2%), headache (15.4%), pyrexia (11.5%), hyperglycemia (11.5%), and aspartate aminotransferase (AST) increase (11.5%), in the combination arm; of these, rash (38.4%), diarrhea (7.7%), and AST increase (7.7%) included Grade 3-4 tx-related AEs. In M-TNBC, 29 pts received atezo + ipat and 24 received capecitabine. Confirmed ORRs were 3.4% (95% CI: 0.1, 17.8) and 20.8% (95% CI: 7.1, 42.2), respectively. Median PFS was 1.7 mo (95% CI: 1.5, 2.8) and 4.1 mo (95% CI: 2.3, 5.7), respectively. Median OS was 10.8 mo (95% CI: 7.0, 18.1) and 15.2 mo (95% CI: 14.4, 20.8). Gr 3-4 AEs were seen in 51.7% and 37.5% of pts, respectively; Gr 5 AEs were seen in 1 pt in the combination arm (encephalitis due to atezo). SAEs occurred in 51.7% and 16.7% of pts, respectively; 6.9% and 4.2% of pts had tx-related AEs leading to tx withdrawal. The most common tx-related AEs were rash (55.2%), diarrhea (48.3%), nausea (37.9%), pyrexia (31.0%), and fatigue (24.1%) in the combination arm; of these, rash (24.1%), fatigue (3.4%), and pyrexia (3.4%) included Gr 3-4 tx-related AEs. Biomarker data, including PI3K pathway status, PD-L1 and CD8-panCK expression, will also be presented. Conclusion: Atezo + ipat + fulv was tolerable with a preliminary efficacy signal in HR+ BC. Atezo + ipat had limited efficacy in biomarker unselected TNBC. Citation Format: Sara A. Hurvitz, Valentina Boni, Elizabeth Comen, Seock-Ah Im, Kyung Hae Jung, Sung-Bae Kim, Keun Seok Lee, Sherene Loi, Hope S. Rugo, Amir Sonnenblick, Melinda L. Telli, Kelly DuPree, Marcella Fasso, Ya-Chen Lin, Mina Nikanjam, Frauke Schimmoller, Xiaosong Zhang, Jing Zhu, Peter Schmid. Phase Ib/II open-label, randomized trial of atezolizumab (atezo) with ipatasertib (ipat) and fulvestrant (fulv) vs control in MORPHEUS-HR+ breast cancer (M-HR+ BC) and atezo with ipat vs control in MORPHEUS triple negative breast cancer (M-TNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-PD10-04
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Heparanase Accelerates Obesity-Associated Breast Cancer Progression
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 20 ( 2019-10-15), p. 5342-5354
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 20 ( 2019-10-15), p. 5342-5354
    Abstract: Obese women have higher risk of bearing breast tumors that are highly aggressive and resistant to therapies. Tumor-promoting effects of obesity occur locally via adipose inflammation and related alterations to the extracellular matrix (ECM) as well as systemically via circulating metabolic mediators (e.g., free fatty acids, FFA) associated with excess adiposity and implicated in toll-like receptor-mediated activation of macrophages—key cellular players in obesity-related cancer progression. Although the contribution of macrophages to proneoplastic effects of obesity is well documented, the role of ECM components and their enzymatic degradation is less appreciated. We show that heparanase, the sole mammalian endoglucuronidase that cleaves heparan sulfate in ECM, is preferentially expressed in clinical/experimental obesity-associated breast tumors. Heparanase deficiency abolished obesity-accelerated tumor progression in vivo. Heparanase orchestrated a complex molecular program that occurred concurrently in adipose and tumor tissue and sustained the cancer-promoting action of obesity. Heparanase was required for adipose tissue macrophages to produce inflammatory mediators responsible for local induction of aromatase, a rate-limiting enzyme in estrogen biosynthesis. Estrogen upregulated heparanase in hormone-responsive breast tumors. In subsequent stages, elevated levels of heparanase induced acquisition of procancerous phenotype by tumor-associated macrophages, resulting in activation of tumor-promoting signaling and acceleration of breast tumor growth under obese conditions. As techniques to screen for heparanase expression in tumors become available, these findings provide rational and a mechanistic basis for designing antiheparanase approaches to uncouple obesity and breast cancer in a rapidly growing population of obese patients. Significance: This study reveals the role of heparanase in promoting obesity-associated breast cancer and provides a mechanistically informed approach to uncouple obesity and breast cancer in a rapidly growing population of obese patients.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-18-4058
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract P3-05-27: The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P3-05-27-P3-05-27
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P3-05-27-P3-05-27
    Abstract: Background: Invasive early breast cancer (IBC) often presents with a co-existing ductal carcinoma in situ (DCIS) component, while about 5% of the cases present with an extensive ( & gt;25%) intraductal component (EIC). The presence of a DCIS component was previously shown to be associated with favorable clinico-pathological characteristics and survival outcomes. However, the association between co-existing DCIS and genomic risk of recurrence is unclear. Methods: Patients with early hormone receptor positive (HR+) HER2neu-negative (HER2-) breast cancer and known OncotypeDX breast recurrence score (RS), who underwent breast surgery in our institute, were included. A natural language processing (NLP) algorithm was used to identify co-existence of extensive DCIS (DCIS-H) and non-extensive DCIS (DCIS-L) in surgical pathological reports. Genomic risk was determined using OncotypeDX RS, while clinical risk was calculated according to the MINDACT criteria, based on tumor size and grade. The genomic and clinical risks of DCIS-H, DCIS-L and pure IBC (No-DCIS) were compared. Results: A total of 45 (5%) DCIS-H cases, 468 (56%) DCIS-L cases and 328 (39%) No-DCIS cases were identified. DCIS-H cases presented with less aggressive clinico-pathological characteristics, such as lower proportions of histologic grade III (10% vs 26% vs 21%) and lower proportions of node-positive disease (13% vs 18% vs 21%), compared to DCIS-L and No-DCIS cases, respectively. The distribution of OncotypeDX RS significantly varied between the groups. DCIS-H tumors were less likely to have a high RS and more likely to have a low or intermediate RS compared to DCIS-L and No-DCIS tumors (High RS: 4% vs 20% vs 20%, Low + intermediate RS: 96% vs 80% vs 80%, respectively; p=0.04). Additionally, the proportions of high clinical risk cases were lower in the DCIS-H group compared to the DCIS-L and No-DCIS groups (42% vs 53% vs 50%, respectively; p=0.002). Based on genomic and clinical risk and current guidelines, we found that women presented with an extensive DCIS component (DCIS-H) had a lower probability of receiving an adjuvant chemotherapy recommendation compared to women presented with a non-extensive DCIS component (DCIS-L) or pure IBC (No-DCIS) (11% vs 29% vs 25%, respectively; p=.035). No differences in disease recurrence were detected between the groups. Conclusions: Co-existing extensive DCIS in invasive early HR+Her2- breast cancer is significantly correlated with lower genomic and clinical risk of recurrence and a smaller chance for chemotherapy recommendation. The rarity of this condition (5% of cases) limited our ability to detect differences in outcomes. These findings warrant future studies of the underlying genomic landscape of co-existing extensive DCIS. Citation Format: Yael Bar, Kfir Bar, Judith Ben- Dror, Didi Feldman, Meishar Shahoha, Ahuva Weiss-Meilik, Nachum Dershowitz, Wolf Ido, Amir Sonnenblick. The impact of co-existing ductal carcinoma in situ in invasive early hormone receptor positive breast cancer on the genomic and clinical risk of recurrence [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-27.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P3-05-27
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract PD10-06: Clinical behavior and outcomes of BRCA -mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PD10-06-PD10-06
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PD10-06-PD10-06
    Abstract: Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS] ) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p & lt;0.001). Compared to mBRCA2 breast cancer pts, those with mBRCA1 were younger, more likely to have reported Jewish ancestry, had more grade 3 tumors, less nodal involvement, lobular histology and HER2 positivity, and received more frequently chemotherapy (all p & lt;0.001). More mBRCA1 pts with hormone receptor-positive tumors did not receive adjuvant endocrine therapy (14.7% vs. 4.2%, p & lt;0.001). No difference between mBRCA1 and mBRCA2 pts was observed in risk-reducing mastectomy (43.9% vs. 46.0%; p=0.371) or salpingo-oophorectomy (48.3% vs. 48.8%; p=1.0). Median follow-up was 7.9 years (range 5.6-10.6 years). Second primary breast cancers (17.0% vs. 12.2%, p=0.025) and non-breast primary malignancies (4.3% vs. 1.9%, p=0.033) were more frequent among mBRCA1 pts compared to mBRCA2 pts, while distant recurrences were less frequent (10.4% vs. 15.4%, p=0.013). 8-year DFS was 62.8% and 65.9% for mBRCA1 and mBRCA2 pts, respectively (adjusted HR 0.76; 95% CI 0.60-0.96). The worse DFS in mBRCA1 was observed regardless of hormone receptor status (pinteraction=0.848): hormone receptor-positive (adjusted HR 0.77; 95% CI 0.58-1.03) and hormone receptor-negative (adjusted HR 0.73; 95% CI 0.48-1.13). No differences in DRFI and OS were observed between mBRCA1 and mBRCA2 pts. Compared to pts with hormone receptor-negative disease, those with hormone receptor-positive breast cancer had higher chances of developing distant (± loco-regional) recurrences (16.1% vs. 9.0%; p & lt;0.001) and less frequent second primary malignancies (BC: 12.1% vs. 17.9%, p=0.005; non-BC: 2.8% vs. 4.0%, p=0.216). No differences in DFS and OS were observed between pts with hormone receptor-positive or negative breast cancer. However, there was a trend towards worse DRFI in women with hormone receptor-positive breast cancer as compared to those with hormone receptor-negative disease (8-year DRFI: 83.4% vs. 90.1%; adjusted HR 1.39; 95% CI 0.94-2.05). Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PD10-06
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 1836: Patient-derived xenograft (PDX) models expressing HER2 reflect clinical responses to targeted HER2 inhibition
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1836-1836
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 1836-1836
    Abstract: Background While HER2-directed agents are most often used for treating breast cancer, there is increasing evidence that these therapies may be of value in other solid tumors. Sequencing efforts and immunohistochemistry (IHC) have identified mutations, amplifications, and overexpression of HER2 in ovarian, HNSCC, NSCLC, and GI cancers. PDX models could permit evaluation of HER2 response/resistance mechanisms to optimize therapeutic strategies. In this pilot study, we evaluated the response of PDX models to HER2-targeted therapies and correlated responses to clinical outcomes. Materials and Methods PDX models were developed from a variety of patient solid tumors, evaluated by IHC for HER2 expression and next-generation sequencing for genomic alterations in HER2 (mutations, amplifications/deletions, and expression levels). Models were screened against single agent HER2-directed therapies including trastuzumab (n=15), trastuzumab emtansine (n=23), and lapatinib (n=10). Tumor regression (TR) values and RECIST criteria were determined and correlated with known literature-based response rates (RR) as well as individual patient outcomes. Results 32 PDX models from 30 patients were interrogated (primarily breast and colorectal). Twenty (63%) models have been sequenced to date; 13 (65%) harbor amplification at ERBB2 gene locus. Further, 56% (18/32) have been evaluated by IHC for HER2 to date: 50% have 2+ HER2 staining, 17% 3+ staining, and 33% 1+/- staining. Based on PDX tumor growth, stable disease/regression was observed in 10% of models screened against lapatinib (CR/PR=0%), 50% screened against trastuzumab (CR/PR=8%), and 67% tested against trastuzumab emtansine (CR/PR=14%). Only models with +2/+3 HER2 staining showed regression with HER2-targeted treatment, with nearly 70% of +1/- HER2 models showing progressive disease. Finally, there were 4 correlations to patient clinical outcomes available, with 3/4 (75%) of the PDX model responses mimicking those of the patient to the same treatment. Conclusion and Future Directions Extensive sequencing of human cancers has demonstrated HER2 amplification or mutation in numerous solid tumors, suggesting HER2-directed therapy could be applied more broadly in the clinic. Consistent with clinical findings, HER2 therapy responses depended upon the strength of HER2 expression (based on IHC). Nevertheless, response rates in PDX models varied depending on which HER2-targeted agent was deployed, highlighting the potential existence of differential mechanisms of de novo resistance/sensitivity. Comprehensive sequencing and drug testing of these PDX models is planned and could allow a deeper understanding of such mechanisms. In this context, application of PDX models for translational modeling of HER2 drug responses, particularly in the context of co-clinical trials, will continue to evolve. Citation Format: Daniel Ciznadija, Amir Sonnenblick, Jennifer Jaskowiak, Angela Davies, David Sidransky. Patient-derived xenograft (PDX) models expressing HER2 reflect clinical responses to targeted HER2 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1836. doi:10.1158/1538-7445.AM2017-1836
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-1836
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Cost Effectiveness of Whole Population BRCA Genetic Screening for Cancer Prevention in Israel
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Prevention Research Vol. 14, No. 4 ( 2021-04-01), p. 455-462
    Details
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 14, No. 4 ( 2021-04-01), p. 455-462
    Abstract: With the growing technical ease and reduction in genetic screening costs, whole population BRCA screening may be a feasible option. Our objective was to investigate the cost effectiveness of whole population screening for BRCA mutations in Israel, for varying degrees of BRCA carrier state. Lifetime costs of whole female population screening for BRCA mutation carrier state versus nonscreening were compared using a Markovian process decision analysis model. Model parameters including ovarian and breast cancer risks were obtained from previously published data. Screening and other treatment-related costs were received from the Israeli Ministry of Health pricing list according to specified codes. Quality-adjusted life years were used for cost-effectiveness analysis. Sensitivity analysis was conducted to evaluate model uncertainties, specifically varying degrees of BRCA prevalence. Results show that whole population BRCA screening in Israel is cost effective across a wide range of BRCA prevalence rates with an incremental cost-effectiveness ratio of 81,493 new Israeli Shekels for a BRCA prevalence of 2.5%, increasing to 250,000 new Israeli Shekels for a 0.75% prevalence rate, per quality-adjusted life year gained. Discount rate and population BRCA prevalence and rate of risk reduction salpingo-oophorectomy are the most influential parameters in the model. Whole population screening for BRCA mutations should be offered as part of general health screening strategies by national medical insurance providers, even for non-Ashkenazi Jews. Our algorithm can be applied for other countries, adjusting local costs of screening and treatment. Prevention Relevance: Whole population BRCA mutation screening in Israel is cost effective across a wide prevalence rate and should be offered as part of general health screening strategies by national medical insurance providers for cancer prevention.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    URL: Article
    DOI: 10.1158/1940-6207.CAPR-20-0411
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2422346-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Abstract P4-10-16: Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P4-10-16-P4-10-16
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P4-10-16-P4-10-16
    Abstract: Purpose We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. Experimental Design The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival (DDFS). Results Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N=209), were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (HR=1.27 p-interaction=0.014 [DCN], HR=1.58, p-interaction=0.027 [PLAU] , HR=1.71, p-interaction=0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR=0.73 p-interaction=0.47 [DCN] , HR=0.71, p-interaction=0.73 [PLAU], HR=0.84; p-interaction=0.36 [HER2STROMA] ). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC & lt;50%). Conclusions Reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy. Citation Format: Amir Sonnenblick, Mali Salmon-Divon, Roberto Salgado, Noam Pondé, Sibylle Loibl, Carsten Denkert, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Amos Azaria, Sherene Loi, Stefan Michiels, Christos Sotiriou. Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-16.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-P4-10-16
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...