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Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients

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Abstract

In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin®) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin® therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV–EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m2; p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m2; p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (−21.0 ± 0.5 vs. −18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.

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Abbreviations

A′:

Late annular velocity

AR:

Atrial reversal

A :

Late diastolic velocity

C :

Anthracycline-embedded chemotherapy

CI:

Confidence interval (25/75 %)

2D-STE:

Two-dimensional speckle tracking echocardiography

Doc:

Docetaxel

DT:

Deceleration time

EC:

Epirubicin–cyclophosphamide

EC/TX/CAP:

Epirubicin–cyclophosphamide/paclitaxel/capecitabine

EF:

Ejection fraction

ERO:

Effective Regurgitate Orifice area

ETC:

Epirubicin–paclitaxel–cyclophosphamide

E′:

Early annular velocity

E :

Early diastolic velocity

FEC:

5-Fluorouracil–epirubicin–cyclophosphamide

FS:

Fractional shortening

GLS:

Global longitudinal strain

IVRT:

Iso-volumetric relaxation time

LA:

Left atrium

LA-VI:

Left atrium volume index

LV:

Left ventricle

LV-DVI:

Left ventricle diastolic volume index

LV-SVI:

Left ventricle systolic volume index

ns.:

Non-significant

nt.:

Not tested

PVD:

Pulmonary diastolic flow velocity

PVS:

Pulmonary systolic flow velocity

RLS:

Regional longitudinal strain

RV:

Right ventricle

RVSP:

Right ventricle systolic pressure

s′ :

TDI mitral valve annular systolic motion

s a :

TDI tricuspid annular systolic motion

SEM:

Standard error of mean

SVI:

Stroke volume index

T :

Trastuzumab

TAC:

Docetaxel–doxorubicin–cyclophosphamide

TAPSE:

Tricuspid annular plane systolic excursion

TDI:

Tissue Doppler imaging

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Authors and Affiliations

  1. Asklepios-Harz-Klinik Goslar, Medizinische Klinik I, Kardiologie, Angiologie, Diabetologie und Internistische Intensivmedizin, Koesliner Str. 12, 38640, Goslar, Germany

    Stefan Andreas Lange

  2. Medizinische Klinik I, Kardiologie und Angiologie, Klinikum Worms, Akademisches Lehrkrankenhaus der Johannes–Gutenberg–Universitaet, Gabriel-von-Seidl-Str. 81, Mainz, Germany

    Jens Jung

  3. Zentrale Krankenhausapotheke, Harzklinikum D. C. Erxleben, Akademisches Lehrkrankenhaus der Otto-von-Guericke Universitaet Magdeburg, Ilsenburger Str. 15, Wernigerode, Germany

    Almut Jaeck

  4. Frauenklinik, Brustzentrum-Perinatalzentrum, Klinikum Worms, Akademisches Lehrkrankenhaus der Johannes–Gutenberg–Universitaet, Gabriel-von-Seidl-Str. 81, Mainz, Germany

    Thomas Hitschold

  5. Medizinische Klinik/Kardiologie, Herzzentrum Dresden, Universitaetsklinik, Technische Universitaet Dresden, Fetscherstr. 76, Dresden, Germany

    Bernd Ebner

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  1. Stefan Andreas Lange
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Correspondence to Stefan Andreas Lange.

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Lange, S.A., Jung, J., Jaeck, A. et al. Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients. Cardiovasc Toxicol 16, 193–206 (2016). https://doi.org/10.1007/s12012-015-9328-9

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