Abstract 518 Long-term cardiac follow Up after dose-dense anthracycline based chemotherapy for breast cancer

Anthracycline based chemotherapy is associated with a life-time dose dependent cardiotoxicity. Previous oncologic studies have shown beneficial therapeutic effects of dose-dense and intense dose-dense regimes for patients with high-risk mamma-carcinoma. However, little is known about the long-term cardiac effects of this treatment strategy compared to conventional anthracycline therapy. 

In a multi-center cohort control study including 123 patients with breast cancer, we investigated the effects of a dose-dense anthracycline based treatment (n=66) with a regular treatment protocol (n=57).  The mean follow up was 113 months. 14 (21.2%) of patients in the dose-dense treatment arm and 20 (35.1%) patients in the control arm died during follow up.  At the end of the follow-up period, all surviving patients enrolled at the main study center (n=70) were invited for a cardiac examination including echocardiography, ECG and biomarkers. 35 patients were successfully screened (16 of the dose-dense and 19 of the control group) while 9 patients declined the invitation as they lived abroad and 24 patients declined for personal reasons in part connected to the COVID-19 pandemic. Two patients were lost to follow-up.

There was no significant difference in left ventricular function (58.07 (±5.40)% vs. 59.58 (±3.70)%, p=0.34), left ventricular strain (-18.32 (±3.09)% vs. -19.78 (2.99±)% p=0.213), conduction time (QRS 86.88 (±6.58) ms vs. 83.63 (±7.62) ms p=0.191, PQ 144.50 (±18.71) ms vs. 160.58 (±28.30) ms p=0.061), repolarization time (QTc 407.25 (±10.45) ms vs. 411.32 (±27.23) ms p=0.578), kidney function (100.10 (±15.34) ml/min1.76m² vs. 94.88 (±14.54) ml/min1.76m² p=0.316) or cardiac biomarkers (BNP 189.88 (±302.09) ng/l vs. 159.53 (±171.75) ng/l p=0.712 and hsTNT 4.88 (±1.67) pg/ml vs. 5.11 (±1.56) pg/ml p=0.676) between the groups, however, a significant reduction in overall mortality and cancer relapse was noted in the dose dense cohort – even when adjusted for receptor status, age, lymph node status, ki67%, grading, and ECOG status (HR 3.7 [1.1;12.1] p=0.0337).

In conclusion, even in a long-term follow-up situation shorter dosing intervals of anthracyclines (dose-dense application) was not associated with an increase in cardiotoxicity, while beneficial effects with regards to cancer outcomes were maintained.  

Clin Res Cardiol (2023). https://doi.org/10.1007/s00392-023-02180-w
Long-term cardiac follow Up after dose-dense anthracycline based chemotherapy for breast cancer
M. Heckmann¹, J. Lehmann², F. Roll¹, N. Frey¹, A. Schneeweiss³, F. Marme⁴, L. H. Lehmann¹
¹Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie, Universitätsklinikum Heidelberg, Heidelberg; ²Rechtsmedizin, Universitätsklinikum Heidelberg, Heidelberg; ³Sektion Gynäkologische Onkologie, Universitätsklinikum Heidelberg, Heidelberg; ⁴Sektion Konservative Gynäkologische Onkologie, Universitätsklinikum Mannheim, Mannheim;
Anthracycline based chemotherapy is associated with a life-time dose dependent cardiotoxicity. Previous oncologic studies have shown beneficial therapeutic effects of dose-dense and intense dose-dense regimes for patients with high-risk mamma-carcinoma. However, little is known about the long-term cardiac effects of this treatment strategy compared to conventional anthracycline therapy.  In a multi-center cohort control study including 123 patients with breast cancer, we investigated the effects of a dose-dense anthracycline based treatment (n=66) with a regular treatment protocol (n=57).  The mean follow up was 113 months. 14 (21.2%) of patients in the dose-dense treatment arm and 20 (35.1%) patients in the control arm died during follow up.  At the end of the follow-up period, all surviving patients enrolled at the main study center (n=70) were invited for a cardiac examination including echocardiography, ECG and biomarkers. 35 patients were successfully screened (16 of the dose-dense and 19 of the control group) while 9 patients declined the invitation as they lived abroad and 24 patients declined for personal reasons in part connected to the COVID-19 pandemic. Two patients were lost to follow-up. There was no significant difference in left ventricular function (58.07 (±5.40)% vs. 59.58 (±3.70)%, p=0.34), left ventricular strain (-18.32 (±3.09)% vs. -19.78 (2.99±)% p=0.213), conduction time (QRS 86.88 (±6.58) ms vs. 83.63 (±7.62) ms p=0.191, PQ 144.50 (±18.71) ms vs. 160.58 (±28.30) ms p=0.061), repolarization time (QTc 407.25 (±10.45) ms vs. 411.32 (±27.23) ms p=0.578), kidney function (100.10 (±15.34) ml/min1.76m² vs. 94.88 (±14.54) ml/min1.76m² p=0.316) or cardiac biomarkers (BNP 189.88 (±302.09) ng/l vs. 159.53 (±171.75) ng/l p=0.712 and hsTNT 4.88 (±1.67) pg/ml vs. 5.11 (±1.56) pg/ml p=0.676) between the groups, however, a significant reduction in overall mortality and cancer relapse was noted in the dose dense cohort – even when adjusted for receptor status, age, lymph node status, ki67%, grading, and ECOG status (HR 3.7 [1.1;12.1] p=0.0337). In conclusion, even in a long-term follow-up situation shorter dosing intervals of anthracyclines (dose-dense application) was not associated with an increase in cardiotoxicity, while beneficial effects with regards to cancer outcomes were maintained.
https://dgk.org/kongress_programme/jt2023/aV1646.html