PO-71 Potential for new trial end point: success of functional mammosphere assay in Thrombin Inhibition Preoperatively (TIP) trial in early breast cancer

PURPOSE Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were nonsignificant. CONCLUSION Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.

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Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer

Journal of Oncology ◽

10.1155/2019/7386734 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Young-Joon Kang ◽

Han-Byoel Lee ◽

Yun Gyoung Kim ◽

JaiHong Han ◽

Yumi Kim ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Prognostic Factor ◽

Progesterone Receptor ◽

Cancer Patients ◽

Early Breast Cancer ◽

Receptor Expression ◽

Breast Cancer Patients ◽

Ki 67 ◽

End Point

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

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PO-36 - Thrombin Inhibition Preoperatively (TIP) in early breast cancer, the first clinical trial of NOACs as an anti-cancer agent: trial methodology

Thrombosis Research ◽

10.1016/s0049-3848(16)30169-4 ◽

2016 ◽

Vol 140 ◽

pp. S189-S190 ◽

Cited By ~ 6

Author(s):

C.C. Kirwan ◽

N.J. Bundred ◽

J. Castle ◽

R. Clarke ◽

C. Dive ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Early Breast Cancer ◽

Trial Methodology ◽

Thrombin Inhibition ◽

Anti Cancer ◽

Cancer Agent

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Disease-free survival (DFS) as surrogate end-point for overall survival (OS) in early breast cancer (EBC): Correlation may be different according to drugs and/or strategies tested

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.6622 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 6622-6622

Author(s):

D. Giannarelli ◽

E. Bria ◽

P. Carlini ◽

M. Di Maio ◽

F. Cuppone ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Early Breast Cancer ◽

Disease Free Survival ◽

Free Survival ◽

End Point ◽

Disease Free

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Longer-Term Assessment of Trastuzumab-Related Cardiac Adverse Events in the Herceptin Adjuvant (HERA) Trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.0463 ◽

2010 ◽

Vol 28 (21) ◽

pp. 3422-3428 ◽

Cited By ~ 174

Author(s):

Marion Procter ◽

Thomas M. Suter ◽

Evandro de Azambuja ◽

Urania Dafni ◽

Veerle van Dooren ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Events ◽

Early Breast Cancer ◽

End Points ◽

Trastuzumab Treatment ◽

End Point ◽

Neo Adjuvant Chemotherapy ◽

Cardiac Adverse Events

Purpose We investigated the incidence of cardiac adverse events in patients with early breast cancer in the Herceptin Adjuvant (HERA) trial who were treated with 1 year of trastuzumab after completion of (neo)adjuvant chemotherapy. Patients and Methods The HERA trial is a three-group, randomized trial that compared 1 year or 2 years of trastuzumab with observation in women with human epidermal growth factor receptor-2 (HER2) –positive early breast cancer. Eligible patients had normal left ventricular ejection fraction (LVEF; ≥ 55%) after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Cardiac function was monitored throughout the trial. This analysis considers patients randomly assigned to 1 year of trastuzumab treatment or observation. Results There were 1,698 patients randomly assigned to observation and 1,703 randomly assigned to 1 year of trastuzumab treatment; 94.1% of patients had been treated with anthracyclines. The incidence of discontinuation of trastuzumab because of cardiac disorders was low (5.1%). At a median follow-up of 3.6 years, the incidence of cardiac end points remained low, though it was higher in the trastuzumab group than in the observation group (severe CHF, 0.8% v 0.0%; confirmed significant LVEF decreases, 3.6% v 0.6%) In the trastuzumab group, 59 of 73 patients with a cardiac end point reached acute recovery; of these 59 patients, 52 were considered by the cardiac advisory board (CAB) to have a favorable outcome from the cardiac end point. Conclusion The incidence of cardiac end points remains low even after longer-term follow-up. The cumulative incidence of any type of cardiac end point increases during the scheduled treatment period of 1 year, but it remains relatively constant thereafter.

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Update for: Thrombin Inhibition Preoperatively (TIP) in Early Breast Cancer, the first clinical trial of DOACs as an anti-cancer agent

Thrombosis Research ◽

10.1016/j.thromres.2018.02.097 ◽

2018 ◽

Vol 164 ◽

pp. S224-S225

Author(s):

J. Castle ◽

J.R. Harvey ◽

R. Clarke ◽

C. Holcombe ◽

A. Volleamere ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Early Breast Cancer ◽

Thrombin Inhibition ◽

Anti Cancer ◽

Cancer Agent

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Thrombin inhibition preoperatively in early breast cancer

http://isrctn.com/ ◽

10.1186/isrctn14785273 ◽

2015 ◽

Author(s):

Binyam Tesfaye

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Thrombin Inhibition

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A Phase II Placebo-Controlled Trial of Neoadjuvant Anastrozole Alone or With Gefitinib in Early Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.6578 ◽

2007 ◽

Vol 25 (25) ◽

pp. 3816-3822 ◽

Cited By ~ 149

Author(s):

Ian E. Smith ◽

Geraldine Walsh ◽

Anthony Skene ◽

Antonio Llombart ◽

José Ignacio Mayordomo ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Phase Ii ◽

Controlled Trial ◽

Geometric Mean ◽

Objective Response ◽

Cancer Resistance ◽

Geometric Mean Ratio ◽

End Point ◽

Clinical Resistance

Purpose Increased epidermal growth factor receptor (EGFR) expression may promote breast cancer resistance to endocrine therapy. We have therefore investigated whether neoadjuvant gefitinib, an EGFR inhibitor, might overcome biologic and clinical resistance to neoadjuvant anastrozole in a phase II placebo-controlled trial. Patients and Methods Postmenopausal women with stage I to IIIB hormone receptor–positive early breast cancer received anastrozole 1 mg daily for 16 weeks and were randomly assigned at a ratio of 2:5:5 to receive, in addition, gefitinib 250 mg/d orally for 16 weeks: placebo 1 tablet/d orally for 2 weeks and then gefitinib for 14 weeks or placebo for 16 weeks. The primary end point was biologic change in proliferation as measured by Ki67 at 2 and 16 weeks; the main secondary end point was overall objective response (OR). Results Two hundred six women were randomly assigned. Mean changes in Ki67 with anastrozole and gefitinib versus anastrozole alone were −77.4% and −83.6%, respectively, between baseline and 16 weeks (geometric mean ratio = 1.37; 95% CI, 0.79 to 2.39; P = .26), −80.1% and −71.3% between baseline and 2 weeks (geometric mean ratio = 0.70; 95% CI, 0.39 to 1.25; P = .22) and −19.3% and −43% (geometric mean ratio = 1.42; 95% CI, 0.86 to 2.35; P = .16) between 2 and 16 weeks. ORs in the combination and anastrozole alone groups were 48% and 61% (estimated difference = −13.1%; 95% CI, –27.3% to 1.2%), respectively, with a nonsignificant trend against the combination (P = .08) and 48% versus 72% (estimated difference = −24.1%; 95% CI, –45.3% to −2.9%) in the progesterone-receptor–positive subgroup, which was significant (P = .03) and consistent with Ki67 changes. Common treatment-related adverse events included diarrhea, rash, alopecia, dry skin, and nausea. There was no evidence of a pharmacokinetic interaction. Conclusion Addition of gefitinib to neoadjuvant anastrozole had no additional clinical or biologic effect, failing to support our original hypothesis.

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Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.19.02750 ◽

2020 ◽

Vol 38 (28) ◽

pp. 3261-3272 ◽

Cited By ~ 6

Author(s):

Adrian Murray Brunt ◽

Joanne S. Haviland ◽

Mark Sydenham ◽

Rajiv K. Agrawal ◽

Hafiz Algurafi ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Controlled Trial ◽

Local Tumor Control ◽

Tumor Control ◽

Breast Radiotherapy ◽

End Point ◽

Whole Breast Radiotherapy ◽

Significant Difference

PURPOSE Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

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