Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Gianni, Luca; Dafni, Urania; Gelber, Richard D.; Azambuja, Evandro de; Muehlbauer, Susanne; Goldhirsch, Aron; Untch, Michael; Smith, Ian; Baselga, J.; Jackisch, Christian; Cameron, David; Mano, Max Senna; Pedrini, José Luiz; Veronesi, Andrea; Mendiola, C.; Płużańska, A; Семиглазов, Владимир; Vrdoljak, Eduard; Eckart, Michael J.; Shen, Zhenzhou; Skiadopoulos, George; Procter, Marion; Pritchard, Kathleen I.; Piccart‐Gebhart, Martine; Bell, Richard H.

doi:10.1016/s1470-2045(11)70033-x

Cited by 569 publications

(342 citation statements)

References 21 publications

Supporting

Mentioning

317

Contrasting

Unclassified

Order By: Relevance

“…Adjuvant chemotherapy based on anthracyclines was used in 94% cases, with 26% treated solely with taxanes; 76% patients received adjuvant radiotherapy. The mean time between diagnosis and the use of trastuzumab was 8.4 months [6].…”

Section: Adverse Eventsmentioning

confidence: 99%

“…In the HERA trial, 5.5% of patients stopped their trastuzumab treatment because of side effects. [6] Serious cardiac complications during adjuvant trastuzumab treatment are estimated to occur for 0.5% of patients, which includes circulatory insufficiency of 0-3.9%. The most common asymptomatic condition in the Polish study population was decreased LVEF (1.81%).…”

Section: Adverse Eventsmentioning

confidence: 99%

“…In the trastuzumab group of the HERA trial a significant decrease in LVEF was seen in 3.6% of patients, and severe heart failure in 0.8%. [6] It should be noted that it was not possible to establish the severity of side effects or complications from our database.…”

Section: Adverse Eventsmentioning

confidence: 99%

See 2 more Smart Citations

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

Jagielska

Czubek

Tałasiewicz

et al. 2018

MCT

View full text Add to dashboard Cite

IntroductionIn patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising. Specific aimThe aim of this study was to assess efficacy of trastuzumab(Herceptin) -comprising adjuvant immunotherapy in terms of overall and diseasefree survival as compared to other adjuvant therapies. Patients Results OS Conclusion These results demonstrate the great benefits of inclusion of immunotherapy as the adjuvant Original ResearchJagielska et al. Molecular and Cellular Therapies (2018) 6:2 c o m p o n e n t a s c u r r e n t l y t h e b e s t o v e r a l l therapeutic strategy for the patients suffering breast cancers. As this strategy greatly exceeds any other therapeutic options available for practicing oncologists at the present time, it definitely justifies allocation of all needed public resources, while assuring highest quality health service for the patients in Poland.

show abstract

Section: Adverse Eventsmentioning

confidence: 99%

Section: Adverse Eventsmentioning

confidence: 99%

See 1 more Smart Citation

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

Jagielska

Czubek

Tałasiewicz

et al. 2018

MCT

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…As a result, these signatures are predictive for ERα + tumors, which represent 60-70% of human BC, but not for HER2 + :ERα − or triple-negative BC (9). Thus, Oncotype, a 21-gene recurrence signature (10), is highly predictive for ERα + [hazard ratio (HR), 4.79] but not other subtypes such as HER2 + (HR, 1.0); the invasiveness gene signature (IGS) generated from CD44 + /CD24 -/low breast TICs (11) scores on ERα + (HR, 2.12) but not HER2 + patients (HR, 0.96) (10) (this study); and a stroma-derived prognostic predictor (SDPP) (12) is shown herein to predict clinical outcome for HER2 + :ERα + but not for HER2 + :ERα − BC.…”

mentioning

confidence: 99%

Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2 ⁺ :ERα ⁻ breast cancer

Liu

Voisin

Bader

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Human Epidermal Growth Factor Receptor 2-positive (HER2 + ) breast cancer (BC) is a highly aggressive disease commonly treated with chemotherapy and anti-HER2 drugs, including trastuzumab. There is currently no way to predict which HER2 + BC patients will benefit from these treatments. Previous prognostic signatures for HER2 + BC were developed irrespective of the subtype or the hierarchical organization of cancer in which only a fraction of cells, tumor-initiating cells (TICs), can sustain tumor growth. Here, we used serial dilution and single-cell transplantation assays to identify MMTV-Her2/Neu mouse mammary TICs as CD24 + :JAG1 − at a frequency of 2-4.5%. A 17-gene Her2-TICenriched signature (HTICS), generated on the basis of differentially expressed genes in TIC versus non-TIC fractions and trained on one HER2 + BC cohort, predicted clinical outcome on multiple independent HER2 + cohorts. HTICS included up-regulated genes involved in S/G2/ M transition and down-regulated genes involved in immune response. Its prognostic power was independent of other predictors, stratified lymph node + HER2 + BC into low and high-risk subgroups, and was specific for HER2 + :estrogen receptor alpha-negative (ERα − ) patients (10-y overall survival of 83.6% for HTICS − and 24.0% for HTICS + tumors; hazard ratio = 5.57; P = 0.002). Whereas HTICS was specific to HER2 + :ERα − tumors, a previously reported stroma-derived signature was predictive for HER2 + :ERα + BC. Retrospective analyses revealed that patients with HTICS + HER2 + :ERα − tumors resisted chemotherapy but responded to chemotherapy plus trastuzumab. HTICS is, therefore, a powerful prognostic signature for HER2 + :ERα − BC that can be used to identify high risk patients that would benefit from anti-HER2 therapy. , and triple-negative (basal-like, Claudin-low) tumors. HER2 + BC is caused by overexpression/amplification of the HER2/ERBB2/NEU tyrosine kinase receptor and constitutes 15-20% of cases. Approximately 50% of these are ERα + tumors, and 50% are ERα − . Current treatment of HER2 + BC involves chemotherapy plus trastuzumab (Herceptin; Genentech), a monoclonal antibody directed against HER2 (1-3). Despite improvement in disease-free survival (DFS) over a 4-y follow-up (4), the cost of trastuzumab, adverse effects such as cardiac failure, and emergence of drug-resistance metastases represent serious limitations for its use, particularly in lowincome countries (5). A prognostic signature that can predict clinical outcome from tumor biopsies at time of presentation may help prioritize patients for anti-HER2 therapy.Because BC consists of several different subtypes, each with distinct pathological features and clinical behaviors, predictive prognostic signatures may need to be developed for each subtype.In addition, many types of cancer exhibit hierarchical organization whereby only a fraction of cells, termed tumor-initiating cells (TICs), sustains growth, whereas the remaining tumor cells, which descend from TICs, have lost their tumorigenic potential (6). HER2/...

show abstract

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Cited by 569 publications

References 21 publications

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

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

Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2 ⁺ :ERα ⁻ breast cancer

Contact Info

Product

Resources

About

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial

Cited by 569 publications

References 21 publications

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

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

Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2 + :ERα − breast cancer

Contact Info

Product

Resources

About

Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2 ⁺ :ERα ⁻ breast cancer