PMID- 28341761 OWN - NLM STAT- MEDLINE DCOM- 20180316 LR - 20181113 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 22 IP - 6 DP - 2017 Jun TI - Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. PG - 642-647 LID - 10.1634/theoncologist.2016-0406 [doi] AB - BACKGROUND: Trastuzumab and pertuzumab are approved for the neoadjuvant treatment of human epidermal growth receptor 2 (HER2)-positive breast cancer, but cardiac safety data is limited. We report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy. METHODS: Fifty-seven patients treated with neoadjuvant dose-dense AC-THP followed by adjuvant trastuzumab-based therapy between September 1, 2013, and March 1, 2015, were identified. The primary outcome was cardiac event rate, defined by heart failure (New York Heart Association [NYHA] class III/IV) or cardiac death. Patients underwent left ventricular ejection fraction (LVEF) monitoring at baseline, after AC, and serially during 1 year of anti-HER2 therapy. RESULTS: The median age was 46 years (range 26-68). Two (3.5%) patients developed NYHA class III/IV heart failure 5 and 9 months after initiation of trastuzumab-based therapy, leading to permanent discontinuation of anti-HER2 treatment. Seven (12.3%) patients developed a significant LVEF decline (without NYHA class III/IV symptoms). The median LVEF was 65% (range 55%-75%) at baseline and 64% (range 53%-72%) after AC, and decreased to 60% (range 35%-70%), 60% (range 23%-73%), 61% (range 25%-73%), and 58% (range 28%-66%) after 3, 6, 9, and 12 months (+/- 6 weeks) of trastuzumab-based therapy. CONCLUSION: The incidence of NYHA class III/IV heart failure after neoadjuvant AC-THP (followed by adjuvant trastuzumab-based therapy) is comparable to rates reported in trials of sequential doxorubicin and trastuzumab. Our findings do not suggest an increased risk of cardiotoxicity from trastuzumab plus pertuzumab following a doxorubicin-based regimen. IMPLICATIONS FOR PRACTICE: Dual anti-human epidermal growth receptor 2 (HER2) therapy with trastuzumab and pertuzumab combined with standard chemotherapy has received accelerated approval for the neoadjuvant treatment of stage II-III HER2-positive breast cancer. Cardiac safety data for trastuzumab and pertuzumab in this setting are limited to clinical trials that utilized epirubicin-based chemotherapy. Formalized investigations into the cardiac safety of trastuzumab and pertuzumab with doxorubicin- (rather than epirubicin) based regimens are important because these regimens are widely used for the adjuvant and neoadjuvant treatment of breast cancer. The known role of HER2 signaling in the physiological adaptive responses of the heart provides further rationale for study on the potential cardiotoxicity of dual anti-HER2 blockade. Findings from this retrospective study provide favorable preliminary data on the cardiac safety of trastuzumab and pertuzumab in combination with a regimen of neoadjuvant doxorubicin and cyclophosphamide followed by paclitaxel, one of the preferred breast cancer treatment regimens, according to the National Comprehensive Cancer Network. CI - (c) AlphaMed Press 2017. FAU - Yu, Anthony F AU - Yu AF AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA yua3@mskcc.org. AD - Department of Cardiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Singh, Jasmeet C AU - Singh JC AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Breast Medicine Services, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Wang, Rui AU - Wang R AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Breast Medicine Services, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Liu, Jennifer E AU - Liu JE AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Cardiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Eaton, Anne AU - Eaton A AD - Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Oeffinger, Kevin C AU - Oeffinger KC AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Division of Survivorship and Supportive Care, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Steingart, Richard M AU - Steingart RM AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Cardiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Hudis, Clifford A AU - Hudis CA AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Breast Medicine Services, Memorial Sloan Kettering Cancer Center, New York, New York, USA. FAU - Dang, Chau T AU - Dang CT AD - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. AD - Department of Breast Medicine Services, Memorial Sloan Kettering Cancer Center, New York, New York, USA. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170324 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 80168379AG (Doxorubicin) RN - 8N3DW7272P (Cyclophosphamide) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - K16AIQ8CTM (pertuzumab) RN - P188ANX8CK (Trastuzumab) RN - P88XT4IS4D (Paclitaxel) SB - IM CIN - Oncologist. 2018 Dec;23(12):e164-e165. PMID: 29895630 CIN - Oncologist. 2018 Dec;23(12):e165-e166. PMID: 30120162 MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects MH - Breast Neoplasms/complications/*drug therapy/pathology MH - Cardiotoxicity/*physiopathology MH - Cyclophosphamide/administration & dosage/adverse effects MH - Doxorubicin/administration & dosage/adverse effects MH - Female MH - Heart/drug effects/*physiopathology MH - Heart Failure/chemically induced/*physiopathology MH - Humans MH - Middle Aged MH - Neoadjuvant Therapy/adverse effects MH - Paclitaxel/administration & dosage/adverse effects MH - Receptor, ErbB-2/antagonists & inhibitors MH - Trastuzumab/administration & dosage/adverse effects MH - Ventricular Dysfunction, Left/chemically induced/*physiopathology PMC - PMC5469581 OTO - NOTNLM OT - Cardiotoxicity OT - Heart failure OT - Pertuzumab OT - Trastuzumab COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2017/03/28 06:00 MHDA- 2018/03/17 06:00 PMCR- 2017/12/01 CRDT- 2017/03/26 06:00 PHST- 2016/10/10 00:00 [received] PHST- 2017/01/16 00:00 [accepted] PHST- 2017/03/28 06:00 [pubmed] PHST- 2018/03/17 06:00 [medline] PHST- 2017/03/26 06:00 [entrez] PHST- 2017/12/01 00:00 [pmc-release] AID - theoncologist.2016-0406 [pii] AID - ONCO12111 [pii] AID - 10.1634/theoncologist.2016-0406 [doi] PST - ppublish SO - Oncologist. 2017 Jun;22(6):642-647. doi: 10.1634/theoncologist.2016-0406. Epub 2017 Mar 24.