Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer

Piccart‐Gebhart, Martine; Procter, Marion; Leyland‐Jones, Brian; Goldhirsch, Aron; Untch, Michael; Smith, Ian; Gianni, Luca; Baselga, José; Bell, Richard H.; Jackisch, Christian; Cameron, David; Dowsett, Mitch; Barrios, Carlos H.; Steger, G.; Huang, Chiun‐Sheng; Andersson, Michael; Inbar, Moshe; Lichinitser, Mikhail; Láng, István; Nitz, Ulrike; Iwata, Hiroji; Thomssen, Christoph; Lohrisch, Caroline; Suter, Thomas M.; Rüschoff, Josef; ý, Tamás Süto; Greatorex, Victoria; Ward, Carol; McFadden, Eleanor; Dolci, Mirko; Gelber, Richard D.

doi:10.1056/nejmoa052306

Cited by 4,500 publications

(2,845 citation statements)

References 34 publications

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“…In a joint analysis from the NSABP (National Surgical Adjuvant Breast and Bowel Project) trial B‐31 and NCCTG (North Central Cancer Treatment Group) trial N9831, the addition of trastuzumab to standard chemotherapy was associated with 33% and 50% improvements in overall and disease‐free survival,25 which persisted at 10 years of follow‐up 26. Similar results were reported from the HERA (Herceptin Adjuvant) trial 27. The BCIRG (Breast Cancer International Research Group) 006 trial extended these findings by showing benefit from trastuzumab regimens both with and without anthracyclines 28.…”

Section: The Benefits Of Her2 Targeted Therapiessupporting

confidence: 53%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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Section: The Benefits Of Her2 Targeted Therapiessupporting

confidence: 53%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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“…EGFR targeting has been successful in the treatment of several cancers 9. The EGFR family consists of at least four members, of which both EGFR and human epidermal growth factor 2 (HER2) are critical targets in cancers including breast and gastric malignancies 10, 11, 12, 13. Cetuximab (CTX), an anti‐EGFR monoclonal antibody, has been widely used particularly for treatment of colorectal and lung cancers 14, 15.…”

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confidence: 99%

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

Kato

Futamura

Kanematsu

et al. 2015

Intl Journal of Cancer

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Targeted molecular therapy is an effective anticancer strategy. Anti‐EGFR monoclonal antibodies such as cetuximab (CTX) have been approved for the treatment of various malignancies, including colorectal cancer (CRC) with wild‐type KRAS. However, their efficacy in patients with KRAS mutations has not been established. Therefore, we investigated whether CTX treatment was effective as a single agent or in combination with zoledronic acid (ZOL) in human CRC cell lines with different KRAS status. CRC cell lines SW48 (wild‐type KRAS) and LS174T (mutant KRAS) were treated with ZOL, CTX and a combination of both drugs. Cytotoxicity was measured using the MTT assay. Changes in the levels of intracellular signaling proteins were evaluated using western blot analysis. Finally, we evaluated the efficacy of the combination treatment in an in vivo xenograft model. We observed that ZOL apparently inhibited growth in both cell lines, whereas CTX showed little effect. ZOL also increased the levels of unprenylated RAS. Combined ZOL and CTX treatment was synergistic in both cell lines and was associated with inhibition of the RAS‐MAPK and AKT‐mTOR signaling pathways. Furthermore, the combination treatment was more effective in suppressing the growth of xenografts derived from both SW48 and LS174T cells; this effect was associated with increased apoptosis. These results demonstrate that ZOL inhibits the growth of colon cancer cells regardless of KRAS status, and combination therapy using ZOL and CTX enhances this growth suppression. These findings suggest a novel strategy for the treatment of CRC independent of KRAS mutational status.

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“…A humanized monoclonal antibody against the extracellular domain of HER2, trastuzumab (Herceptin ® , Genentech, San Francisco, CA) has been shown to benefit patients with HER2+ breast cancer, alone or in combination with chemotherapy 4, 5. Adverse events typically associated with chemotherapy, such as alopecia, myelosuppression, and nausea and vomiting are not seen with trastuzumab.…”

Section: Introductionmentioning

confidence: 99%

“…Adverse events typically associated with chemotherapy, such as alopecia, myelosuppression, and nausea and vomiting are not seen with trastuzumab. Cardiotoxicity, either leading to an asymptomatic decrease in left ventricular ejection fraction (LVEF) or heart failure (HF), remains the most important adverse effect 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16…”

Section: Introductionmentioning

confidence: 99%

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

Nowsheen

Aziz

Park

et al. 2018

JAHA

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BackgroundTrastuzumab is life‐extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline.Methods and ResultsWe performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre‐ and on‐therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function (LVEF 63.4±5%) and 20 had an impaired cardiac function (LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF, compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation (P=NS). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF (P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%.ConclusionsWomen undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co‐managed by a cardiologist.

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Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer

Abstract: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)

Cited by 4,500 publications

References 34 publications

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

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