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Anthracycline Use for Early Stage Breast Cancer in the Modern Era: a Review

  • Breast Cancer (ML Telli, Section Editor)
  • Published:
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Opinion statement

Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20–30%. Anthracycline toxicities include the rare—but potential morbid—cardiotoxicity or leukemogenic effect, and the almost universal—but very distressing—alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer. Current literature supports that anthracyclines are not required for all patients with breast cancer and should be avoided in those with high cardiac risk. Recent results from the ABC trials suggest that anthracyclines should not be spared for patients with triple negative breast cancer (regardless of axillary node involvement) or HER2−/ER+ with significant node involvement. Based on current literature, for HER2-negative patients with low-risk breast cancer, anthracyclines could be spared with regimens such as cyclophosphamide, methotrexate, and fluorouracil (CMF) or docetaxel and cyclophosphamide (TC). Patients with intermediate or high-risk breast cancer should be considered for anthracycline-based regimens based on other factors such as age, comorbidities, tumor grade, lymphovascular invasion, and genomic profiling. Patients with HER2-positive breast cancer with low risk could be treated with paclitaxel and trastuzumab. For the remaining patients with HER2 overexpression, while docetaxel, carboplatin, and trastuzumab (TCH) has demonstrated to improve disease-free survival (DFS), anthracycline-containing regimens should be discussed, especially for those with very high-risk breast cancer. Although several biomarkers, such as topoisomerase II (TOP2A) and chromosome 17 centromeric duplication (Ch17CEP) have been proposed to predict benefit from anthracycline regimens, further research is required to delineate their proper utility in the clinical setting.

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Abbreviations

BC:

Breast cancer

OS:

Overall survival

TOP2A:

Topoisomerase 2A

ROS:

Reactive oxygen species

SEER:

Surveillance, Epidemiology, and End Results

LVEF:

Left ventricular ejection fraction

CHF:

Congestive heart failure

HR:

Hazard ratio

RR:

Relative risk

NSABP:

National Surgical Adjuvant Breast and Bowel Project

ASCO:

American Society of Clinical Oncology

AML:

Acute myelogenous leukemia

MDS:

Myelodysplastic syndrome

DFS:

Disease-free survival

CMF:

Cyclophosphamide, methotrexate, and fluorouracil

L-PAM:

L-Phenylalanine mustard

PAF:

L-PAM and fluorouracil

PR:

Progesterone receptor

ER:

Estrogen receptor

AC:

Doxorubicin and cyclophosphamide

CEF:

Cyclophosphamide, epirubicin, and fluorouracil

TC:

Docetaxel and cyclophosphamide

FAC:

Doxorubicin, cyclophosphamide, and fluorouracil

FASG:

French Adjuvant Study Group

TaxAC:

Taxane and anthracycline-based regimen

TNBC:

Triple negative breast cancer

EFS:

Event-free survival

ACTH:

AC plus docetaxel and trastuzumab

TCH:

Docetaxel, carboplatin, and trastuzumab

FEC100:

Fluorouracil, epirubicin, and cyclophosphamide

EC-D:

Epirubicin and cyclophosphamide followed by docetaxel

Ch17CEP:

Chromosome 17 centromeric duplication

CDK4/6:

Cyclin-dependent kinases 4/6

Rb:

Retinoblastoma

E2F:

Elongation factor 2

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Acknowledgements

The manuscript development is supported by The Einstein Paul Calabresi Career Development Program (NIH 5K12CA132783-08) and NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA (Grant Number UL1TR001073).

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Authors and Affiliations

  1. Department of Oncology, Section of Breast Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Sakshi Jasra MD & Jesus Anampa MD

  2. Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Sakshi Jasra MD

  3. Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1695 Eastchester Rd., Bronx, NY, 10461, USA

    Jesus Anampa MD

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Jasra, S., Anampa, J. Anthracycline Use for Early Stage Breast Cancer in the Modern Era: a Review. Curr. Treat. Options in Oncol. 19, 30 (2018). https://doi.org/10.1007/s11864-018-0547-8

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