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Background: Pregnancy after breast cancer (BC) is of substantial importance for many young women at diagnosis and during follow-up. BC treatment including standard endocrine therapy (ET) (5-10 years) may reduce ovarian reserve and the chances of subsequent successful pregnancy, given conception is contraindicated during ET. A temporary interruption of ET to attempt and carry a pregnancy in this population has never been prospectively studied. Methods: POSITIVE is a single-arm, prospective, investigator-initiated, international trial evaluating the safety and pregnancy outcomes of interrupting ET for young women with early-stage hormone-receptor-positive (HR+) BC who desire pregnancy. The primary objective is to assess the risk of BC relapse associated with ET interruption for ~2 years to achieve pregnancy. Women ≤42 years with stage I-III HR+ BC who received adjuvant ET (SERM alone, GnRH analogue plus SERM or AI) for 18 to 30 months and wished to interrupt ET to attempt pregnancy were eligible. The primary endpoint is breast cancer free interval (BCFI) defined as the time from enrollment to the first BC event (local, regional, distant recurrence or a new invasive contralateral BC). Planned sample size was 500 patients. Three interim analyses of BCFI were reviewed by the Data Safety Monitoring Committee (DSMC) to assure a 95% chance of stopping the trial early if the annual BCFI event rate exceeded 4%; with primary analysis triggered after 1600 patient years of follow-up (pyfu) and no more than 46 BCFI events defined as the safety threshold. The DSMC recommended continuing the study following each interim analysis. We now report the primary results. Results: From 12/2014 to 12/2019, 518 women were enrolled. At enrollment, the median age of participants was 37 years (27-43 years); 75.0% were nulliparous, 93.4% had stage I/II disease, 66.3% node-negative. Median time from BC diagnosis to enrollment was 29 months (IQR: 25-32). Tamoxifen alone was the most prescribed ET (41.7%), followed by tamoxifen+ovarian function suppression (35.7%). 62.0% of participants had received neo/adjuvant chemotherapy. At a median follow-up of 41 months (1638 pyfu), 44 participants had experienced a BCFI event, not exceeding the pre-specified safety threshold of 46 events. The 3-year BCFI failure percent was 8.9% (95% CI: 6.3 to 11.6%), similar to the 9.2% (95% CI: 7.6 to 10.8%) calculated in the comparative external control cohort from the SOFT/TEXT trials (Sun et al, Breast 2020). Of 497 women followed for pregnancy status, 368 (74.0%) had at least one pregnancy, 317 (63.8%) had at least one live birth, with a total of 365 babies born. Based on competing risk analysis, 76.3% of patients resumed ET (half within 26 months), 8.3% had BCFI event/death before ET resumption, and 15.4% had not resumed ET yet. Conclusions: The POSITIVE trial demonstrates that for young women with early HR+ BC desiring pregnancy, temporary interruption of ET to attempt pregnancy does not confer a greater short-term risk of recurrence than that observed in a modern historical control group that did not interrupt ET. Most participants have had a live birth. Further follow-up is planned to confirm long-term safety. These results should be considered in counselling BC patients desiring future pregnancy. Citation Format: Ann Partridge, Olivia Pagani, Samuel M. Niman, Monica Ruggeri, Fedro Alessandro A. Peccatori, Hatem A. Azim, Marco Colleoni, Cristina Saura, Chikako Shimizu, Anna Saetersdal, Judith Kroep, Audrey Mailliez, Ellen Warner, Virginia F. Borges, Frédéric Amant, Andrea Gombos, Akemi Kataoka, Christine Rousset-Jablonski, Simona Borstnar, Junko Takei, Jeong Eon Lee, Janice Walshe, Manuel Ruiz Borrego, Halle Moore, Christobel Saunders, Vesna Bjelic-Radisic, Snezana Susnjar, Fatima Cardoso, Karen L. Smith, Teresa Ferreiro Vilarino, Karin Ribi, Kathryn Ruddy, Sarra El-Abed, Martine Piccart, Larissa A. Korde, Aron Goldhirsch, Richard D. Gelber. Pregnancy Outcome and Safety of Interrupting Therapy for women with endocrine responsIVE breast cancer: Primary Results from the POSITIVE Trial (IBCSG 48-14/BIG 8-13) [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 GS4-09.

Background: The addition of trastuzumab (H) to pre-operative chemotherapy in HER2+ breast cancer (H+BC) increases the rate of pathological complete response (pCR). TCH is a widely used adjuvant regimen in early stage H+BC. Lapatinib (L) is a small molecule HER2 antagonist that produces responses following H failure, and has been reported to augment H activity in combination in vitro. We compared neo-adjuvant docetaxel, carboplatin (TC) + H v TCL v TCHL in pts with H+BC. Methods: Pts with stages Ic–III H+BC were randomized to receive neo-adjuvant TCH, TCL or TCHL (ICORG/CTRIAL-IE 10-05, NCT01485926 www.clinicaltrials.gov). Pts subsequently underwent surgery and received H post-operatively for 1 year from the first dose of H. The primary endpoint of the trial was pCR. Secondary objectives were overall survival (OS) and relapse-free survival (RFS) and molecular and pharmacological markers of response. This study was supported by GSK, Novartis, The Cancer Clinical Research Trust and The Caroline Foundation. Results: When the NCIC CTG MA.31 trial reported inferior outcomes for L compared to H, we discontinued the TCL arm. This abstract reports data on the 76 pts recruited to the TCH and TCHL arms only, who included stage II (69.7%; n=53) or stage III disease (21.1%; n=16, with stage unknown for 9.2% (n=7). The final analysis set numbered 75 pts. Clinicopathological characteristics were well balanced between arms. The pCR rate of the two arms TCHL and TCH were virtually identical at 51.6% and 52.8% respectively (Fisher’s test p-value: 1.000). TCHL pts had significantly superior 5 year relapse-free survival (relative risk (RR) 0.171, 95% CI 0.041 – 0.713; log-rank test p-value = 0.009). OS was comparable between the TCH and TCHL groups (RR 0.205, 95% CI 0.025 – 1.675); log-rank test p-value = 0.2). Median RFS and OS were not reached. The most frequent serious adverse event was diarrhoea which occurred in 21.3% (n=16/75) pts (Grade 3 diarrhoea 13/16). One pt (TCH arm) who did not have protocol-mandated prophylactic G-CSF had a Grade 5 toxicity. One TCHL pt had a self-limiting diverticular perforation. There was a significantly higher frequency of severe diarrhoea in pts who received the TCHL regimen (Grade 3+, 32.4% vs 10.5%, p=0.038). The use of prophylactic loperamide reduced the frequency of diarrhoea in both the TCHL arm (86.2% vs 44.4%, p=0.004) and in the TCH arm (58.8% vs 24%, p=0.009). A post lock audit with minimum 9-year follow-up showed relapse rates of 15% TCHL vs 33% TCH. Conclusions: The study did not meet its primary pCR endpoint possibly due to a high TCH pCR rate, and small numbers. TCHL produced a statistically significant improvement in RFS compared to TCH. TCHL produced a higher rate of gastro-intestinal toxicity, but the use of loperamide significantly reduced the frequency of diarrhoea. These data suggest that anti-HER2 TKIs merit further investigation in the neo-adjuvant treatment of early stage H+BC. Table 1. pCR rates, 5 year RFS and OS results for ICORG/CTRIAL-IE 10-05 (NCT01485926) study pts. * significant, p Citation Format: John Crown, Denis M. Collins, Alex J. Eustace, Maccon Keane, Linda Coate, John Kennedy, Seamus O’Reilly, Catherine Kelly, Miriam O’Connor, Michael J. Martin, Conleth Murphy, Karen Duffy, Janice Walshe, Thamir Mahgoub, Giuseppe Gullo, Brian Moulton, Alberto Alvarez-Iglesias, Imelda Parker, Bryan Hennessy. Five year follow up of a randomized phase II comparison of neo-adjuvant docetaxel, carboplatin, trastuzumab with or without lapatinib in HER-2 positive breast cancer [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 P1-11-09.

Background The aims of this study were to explore the impact of COVID-19 on health-care services and quality of life (QoL) in women diagnosed with breast cancer (BC) in Ireland and whether the impact varied by social determinants of health (SDH). Methods Women diagnosed with BC completed a questionnaire measuring the impact of COVID-19, disruption to BC services, QoL, SDH, and clinical covariates during COVID-19 restrictions. The association between COVID-19 impact and disruption to BC services and QoL was assessed using multivariable regression with adjustment for SDH and clinical covariates. An interaction between COVID-19 impact and health insurance status was assessed within the regression models. Results A total of 30.5% (n = 109) of women reported high COVID-19 impact, and these women experienced more disruption in BC services (odds ratio = 4.95, 95% confidence interval = 2.28 to 10.7, P Conclusions There was a large disruption to BC services and decrease in QoL for women with BC in Ireland during the pandemic. However, the impact was not the same for all women. It is important that women with BC are reintegrated into proper care and QoL is addressed through multidisciplinary support services.

Background The Clinical Treatment Score post-5 years (CTS5) integrates four clinicopathological variables to estimate the residual disease recurrence risk in hormone receptor-positive breast cancer patients who have been treated with five years of adjuvant endocrine therapy. This study aimed to determine the accuracy of the CTS5. Methods A systematic review was performed in accordance with the PRISMA statement. Studies relevant for inclusion in the current review were identified from The Cochrane Library, EBSCO, Ovid, PubMed, and Embase. Results Six papers reported on 30 354 postmenopausal patients (age range 42 to 91 years). The pooled hazard ratio (HR) of distant recurrence relative to the low-risk CTS5 category was 5.41 (95% c.i. 4.50 to 6.51; P < 0.05) for the high-risk CTS5 category and 2.32 (95% c.i. 1.90–2.84; P < 0.05) for the intermediate CTS5 category. Three papers reported on 10 425 premenopausal patients (age range 18 to 54 years). The pooled HR of distant recurrence relative to the low-risk CTS5 category was 5.42 (95% c.i. 2.26 to 13.01; P < 0.05) for the high-risk CTS5 category and 2.82 (95% c.i. 1.35 to 5.88; P < 0.05) for the intermediate CTS5 category. Relative to high-risk postmenopausal patients, the mean observed 10-year distant recurrence risk for the high CTS5 category was 13.83 per cent, which differs significantly from the CTS5 estimation of 10-year distant recurrence risk (20.3 per cent, 95% c.i. 17.2 to 24; P = 0.000). Conclusion The CTS5 can predict late distant recurrence risk in pre- and postmenopausal hormone receptor-positive breast cancer patients. CTS5 overestimates the risk for high-risk patients and thus, its use in these patients warrants caution.

Purpose The aim of this study is to understand the impact of COVID-19 on breast cancer (BC) services and quality of life (QoL) in women living with and beyond BC in Ireland and whether the impact varied by social determinants of health (SDH). Methods The survey study invited women diagnosed with BC in the past five years to complete a questionnaire measuring the impact of COVID-19, disruption to BC services, QoL, SDH, and clinical covariates during a period of COVID-19 restrictions. The association between COVID-19 impact, disruption to BC services, and QoL was assessed using logistic and linear regression respectively with adjustment for SDH and clinical covariates. Interactions between COVID-19 impact and SDH were explored. Results 30.5% of women reported a high COVID-19 impact, which was associated with younger age, urban living, and employment status. Over half of all women reported disrupted BC services. A high COVID-19 impact was associated with more disruption to BC services and lower QoL scores. Women in post-active treatment and further removed from their diagnosis reported significantly more disruption to BC services. Younger women and women not employed reported significantly lower QoL scores. Additionally, there were significant interactions between health insurance status and COVID-19 impact on both outcomes. Conclusion The COVID-19 pandemic has significantly impacted women with a prior diagnosis of BC in Ireland, and this impact varied by SDH, including age, region, employment status, and health insurance status. Further research is needed to understand the long-term impact of the pandemic on women with BC.

Background Activation of the phosphoinositide -3 kinase (PI3K) pathway is a resistance mechanism to anti-HER2 targeted therapy. This trial was conducted to determine the maximum tolerated dose (MTD) of copanlisib, an oral pan-class I PI3K inhibitor, combined with trastuzumab for patients with advanced HER2 positive breast cancer resistant to anti-HER2 therapy. Patients and Methods In this phase Ib open label dose escalation study, using a 6 + 6 design, patients with advanced HER2-positive breast cancer who had disease progression following at least one prior line of HER2 therapy in the metastatic setting were treated with a dose escalation schedule of copanlisib (dose level 1 =45mg or dose level 2 = 60mg) IV on days 1, 8 and 15 of a 28 day cycle along with a fixed dose of trastuzumab 2mg/kg weekly after a loading dose of 4mg/kg in cycle 1. Archival tumour tissue, voluntary serial tumour biopsies and serial plasma samples were collected for genomic sequencing. Results Twelve patients were enrolled. MTD was determined as copanlisib 60mg plus trastuzumab 2mg/kg weekly. There was no dose limiting toxicity. The most common treatment-related adverse events (AE) of any grade experienced in more than 2 patients were hyperglycemia (58%), fatigue (58%), nausea (58%) and hypertension (50%). Confirmed stable disease at 16 weeks was observed in 6 (50%) participants. PIK3CA mutations were detected in archival tumour tissue of 6 (50%) patients and did not appear to influence likelihood of clinical benefit. PIK3CA mutations were detected in serial plasma ctDNA of all 12 patients and fluctuated over the course of treatment. Next-Generation Sequencing (NGS) analysis identified novel somatic mutations in the TTRAP gene, which encodes a PI3K-like protein kinase, detected only in tumour samples obtained at metastatic time points. Additionally, NGS analysis demonstrated clear temporal genomic heterogeneity with decreasing PIK3CA mutation variant allele frequency (VAF) post therapy Conclusions The combination of copanlisib and trastuzumab was safely administered with good overall tolerability in this trial. Preliminary anti-tumour stability was observed in patients with heavily pre-treated metastatic HER2 positive breast cancer. Translational studies identified a number of potential biomarkers for further study in the now initiated phase 2 clinical trial. Citation Format: Niamh M Keegan, Simon Furney, Janice Walshe, Giuseppe Gullo, John Kennedy, Kyran Bulger, John McCaffrey, Catherine M Kelly, Keith Egan, P O'Donovan, Andres Hernando, Ausra Teiserskiene, Imelda Parker, Angela M Farrelly, Aoife Carr, Giulio Calzaferri, Ray McDermott, Maccon M Keane, Liam Grogan, Oscar S Breathnach, Patrick G Morris, Sinead Toomey, Bryan T Hennessy. A phase Ib trial of copanlisib in combination with trastuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER” [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 P1-19-24.

To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre.Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival.39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count5% at diagnosis, previous haematological disorder, lower risk IPSS-R and a normal karyotype. Four out of five patients who received intensive therapy/transplant remain alive with median OS of 14 months. Median OS of Azacitidine-treated group was 11 months.t-MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

Background: The 21 gene recurrence score (OncotypeDx ®) is reimbursed in Ireland to guide adjuvant treatment decisions for ER+, LN-negative, human epidermal growth factor receptor 2 (HER2)-negative BC. There is emerging evidence supporting the clinical utility of this test in patients with LN+ disease. Although the exact cut-off for chemotherapy has not been defined in this population, SEER data support the omission of chemotherapy for patients with RS Results: In total, 294 patients were enrolled across the - nine centres. Complete data is available on 123 patients (range 38 to 75, median 54 years), which included two male patients. Of the remaining 121 (98%) patients, 49 (40%) were premenopausal, 26 (21%) perimenopausal and 46 (37%) postmenopausal. The median tumour size was 38 mm (Range 7 to 58 mm). There were 101 (82%) patients with invasive ductal carcinoma, 17 (14%) with lobular carcinoma and 5 (4%) classified as other breast histology. Seventeen patients (14%) had grade 1, 74 (60%) grade 2 and 32 (26%) grade 3 disease. There were 79 (64%) patients with 1 LN+, 35 (29%) with 2 LN+ and 9 (7%) with 3 LN+ status. Overall access to the 21 gene RS test led to a 32% reduction in chemotherapy, 112 (91%) to 72 (59%) patients. This was most notable in patients with ductal histology (91 vs 61) and grade 2 breast cancer (66 vs 41) representing a 24.4% and 20.3% reduction, respectively. Similarly patients with 1 LN+ (71 vs 46) and 2 LN+ (34 vs 21) represented a 20.3% and 9.7% reduction, respectively. This study also identified four patients aged less than 40, for whom chemotherapy was not recommended. The biggest reduction in chemotherapy occurred in women aged over 50 (62 vs 36) at 21.1%. Overall, in 65% of cases, medical oncologists deemed the RS test result significantly changed treatment recommendations. Conclusion: These findings are consistent with results from similar studies in other countries. Broader access to the 21-gene RS could result in a reduction in the use of chemotherapy in Ireland. Citation Format: William J Mullally, Dara Bracken-Clarke, Andrew Padmore, Seamus O'Reilly, Deirdre O’Mahony, Janice Walshe, John Kennedy, Rajnish Gupta, Cathy Kelly, Miriam O'Connor, Karen Duffy, Maccon Keane, Bryan T Hennessy, Patrick G Morris. The impact of the 21 gene recurrence score (RS) on chemotherapy prescribing in estrogen receptor positive (ER+), lymph node positive (LN+) breast cancer (BC) in Ireland: A national, multi-centre, prospective study [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 P3-08-56.

Supplemental material, Supplementary_Table_2 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Table_1 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Table_3 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Table_3 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Table_1 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Methods for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Table_2 for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology

Supplemental material, Supplementary_Methods for Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08–10 trial by Giuseppe Gullo, Alex J. Eustace, Alexandra Canonici, Denis M. Collins, Michael J. Kennedy, Liam Grogan, Oscar Breathhnach, John McCaffrey, Maccon Keane, Michael J. Martin, Rajnish Gupta, Gregory Leonard, Miriam O’Connor, Paula M. Calvert, Paul Donnellan, Janice Walshe, Enda McDermott, Kathleen Scott, Andres Hernando, Imelda Parker, David W. Murray, Alice C. O’Farrell, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Norma O’Donovan, William M. Gallagher, Bonnie Ky, Dimitrios Tryfonopoulos, Brian Moulton, Annette T. Byrne and John Crown in Therapeutic Advances in Medical Oncology