Association of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

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Real-World Setting Cost-Effectiveness Analysis Comparing Three Therapeutic Schemes of One-Year Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer from the Cyprus NHS Payer Perspective

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17124339 ◽

2020 ◽

Vol 17 (12) ◽

pp. 4339

Author(s):

Savvas S. Ioannou ◽

Yiola Marcou ◽

Eleni Kakouri ◽

Michael A. Talias

Keyword(s):

Breast Cancer ◽

Cost Effectiveness ◽

Early Breast Cancer ◽

Real World ◽

Cost Effective ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Lifetime Horizon ◽

Effectiveness Analysis ◽

One Year

Introduction: This study is one of the first real-world cost-effectiveness analyses of one-year adjuvant trastuzumab used in HER2-positive early female breast cancer in comparison to chemotherapy alone. It is just the second one in Europe, the first one in Cyprus, and the fourth one worldwide ever carried out using real-world data. Methods: Using a Markov model (four health states), a cost-effectiveness analysis was carried out both over 20 years and for a lifetime horizon. The sampling method used in this study was the randomized sampling of 900 women. Results: The findings for the 20-year horizon showed that all trastuzumab arms were more cost-effective, with a willingness-to-pay threshold of only €60,000 per quality-adjusted life year (QALY) [incremental cost-effectiveness ratios (ICER): €40,436.10/QALY]. For the lifetime horizon, with thresholds of €20,000, €40,000, and €60,000/QALY, all trastuzumab arms were found to be more cost-effective (ICER: €17,753.85/QALY). Moreover, for the 20-year and the lifetime horizons, with thresholds of €20,000/QALY, €40,000/QALY, and €60,000/QALY, the most cost-effective of the three subgroups (anthracyclines and then trastuzumab, no anthracyclines and then trastuzumab, and anthracyclines, taxanes, and trastuzumab) was that of anthracyclines and then trastuzumab (ICER: €18,301.55/QALY and €8954.97/QALY, respectively). Conclusions: The study revealed that adjuvant trastuzumab for one year in female HER2-positive early breast cancer can be considered cost-effective.

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Efficacy and cardiac safety of adjuvant trastuzumab-based chemotherapy regimens for HER2-positive early breast cancer

Annals of Oncology ◽

10.1093/annonc/mdq096 ◽

2010 ◽

Vol 21 (11) ◽

pp. 2153-2160 ◽

Cited By ~ 53

Author(s):

R.B. Costa ◽

G. Kurra ◽

L. Greenberg ◽

C.E. Geyer

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Cardiac Safety ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: a retrospective substudy of the HERA trial (BIG 1-01)

The Lancet Oncology ◽

10.1016/s1470-2045(13)70017-2 ◽

2013 ◽

Vol 14 (3) ◽

pp. 244-248 ◽

Cited By ~ 95

Author(s):

Bernhard C Pestalozzi ◽

Eileen Holmes ◽

Evandro de Azambuja ◽

Otto Metzger-Filho ◽

Laurence Hogge ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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Abstract P4-12-02: Adjuvant trastuzumab improved the prognosis of HER2-positive early breast cancer: Single institutional cohort study from clinical practice

10.1158/1538-7445.sabcs15-p4-12-02 ◽

2016 ◽

Author(s):

S Akiyoshi ◽

M Ishida ◽

C Koga ◽

Y Nakamura ◽

K Taguchi ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Clinical Practice ◽

Early Breast Cancer ◽

Her2 Positive ◽

Adjuvant Trastuzumab

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Extracellular Matrix Features Discriminate Aggressive HER2-Positive Breast Cancer Patients Who Benefit from Trastuzumab Treatment

Cells ◽

10.3390/cells9020434 ◽

2020 ◽

Vol 9 (2) ◽

pp. 434

Author(s):

Ilona Rybinska ◽

Marco Sandri ◽

Francesca Bianchi ◽

Rosaria Orlandi ◽

Loris De Cecco ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Gene Expression Pattern ◽

Response To Therapy ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Adjuvant Trastuzumab ◽

Trastuzumab Treatment ◽

Worse Prognosis

We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25–37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment.

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