Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831

Perez, Edith A.; Romond, Edward H.; Suman, Vera J.; Jeong, Jong‐Hyeon; Sledge, George W.; Geyer, Charles E.; Martino, Silvana; Rastogi, Priya; Gralow, Julie R.; Swain, Sandra M.; Winer, Eric P.; Colón‐Otero, Gerardo; Davidson, Nancy E.; Mamounas, E.; Zujewski, Jo Anne; Wolmark, Norman

doi:10.1200/jco.2014.55.5730

Cited by 852 publications

(681 citation statements)

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“…With the application of HER‐2 fluorescent in situ hybridization and HER‐2 immunohistochemistry which are standard clinical tests for HER‐2 gene amplification 35, 36, HER‐2 gene amplification or protein overexpression has been extensively studied in breast cancer 37, 38, 39, 40, much less is known about genetic variants and mutations that might have an impact on the risk or therapy of breast cancer. It may be more challenged to successfully target HER‐2 mutations than EGFR mutation.…”

Section: Introductionmentioning

confidence: 99%

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Sun

Shi

Shen

et al. 2015

J Cellular Molecular Medi

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Studies over the last two decades have identified that amplified human epidermal growth factor receptor (HER‐2; c‐erbB‐2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer. Lots of painstaking efforts were invested on the HER‐2 targeted agents, and significantly improved outcome and prolonged the survival of patients. However, some patients classified as ‘HER‐2‐positive’ would be still resistant to the anti‐HER‐2 therapy. Various mechanisms of drug resistance have been illustrated and the alteration of HER‐2 was considered as a crucial mechanism. However, systematic researches in regard to the HER‐2 mutations and variants are still inadequate. Notably, the alterations of HER‐2 play an important role in drug resistance, but also have a potential association with the cancer risk. In this review, we summarize the possible mutations and focus on HER‐2 variants’ role in breast cancer tumourigenesis. Additionally, the alteration of HER‐2, as a potential mechanism of resistance to trastuzumab, is discussed here. We hope that HER‐2 related activating mutations could potentially offer more therapeutic opportunities to a broader range of patients than previously classified as HER‐2 overexpressed.

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Section: Introductionmentioning

confidence: 99%

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Sun

Shi

Shen

et al. 2015

J Cellular Molecular Medi

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“…The introduction of HER2‐directed therapy has revolutionized the treatment and survival expectations for women with HER2+ breast cancer,25 even for those with metastatic disease 26. Our data suggest that such lifesaving therapy should not be withheld out of concern of a higher cardiotoxicity risk in most women with a reduced cardiac function.…”

Section: Discussionmentioning

confidence: 87%

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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“…The development of the first anti-HER2-targeted therapy with trastuzumab more than 15 years ago has significantly improved the survival of breast cancer patients in 3 Newer agents such as lapatinib, pertuzumab, and an antibody-drug conjugate trastuzumab emtansine (T-DM1), have shown prolongation of diseasefree survival. 4 Dual blockade using trastuzumab and pertuzumab has shown prolonged survival in patients with advanced HER2-positive cancer when compared with trastuzumab alone.…”

Section: Targeted Therapy For Her2-positive Breast Cancermentioning

confidence: 99%

Recent advances in breast cancer treatment

Cheung¹

2018

Hong Kong Med J

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Trastuzumab Plus Adjuvant Chemotherapy for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Planned Joint Analysis of Overall Survival From NSABP B-31 and NCCTG N9831

Cited by 852 publications

References 10 publications

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

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

Recent advances in breast cancer treatment

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