scholarly journals Testing for HER2 in Breast Cancer: A Continuing Evolution

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Sejal Shah ◽  
Beiyun Chen
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Humanized Monoclonal Antibody ◽  
Epidermal Growth ◽  
Invasive Breast Carcinomas ◽  
Disease Free

Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.

scholarly journals Multicenter study of primary systemic therapy with docetaxel, cyclophosphamide and trastuzumab for HER2-positive operable breast cancer: the JBCRG-10 study

2019 ◽  
Vol 50 (1) ◽  
pp. 3-11
Author(s):  
Takayuki Ueno ◽  
Norikazu Masuda ◽  
Nobuaki Sato ◽  
Shoichiro Ohtani ◽  
Jun Yamamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathological Complete Response ◽  
Complete Response Rate ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Complete Response ◽  
Primary Systemic Therapy ◽  
Free Survival ◽  
Epidermal Growth ◽  
Disease Free

Abstract Background The original aim of this study was to evaluate the treatment sequence and anthracycline requirement in docetaxel, cyclophosphamide and trastuzumab therapy. After one death in the anthracycline-containing arm, the protocol was amended to terminate the randomization. The single-docetaxel, cyclophosphamide and trastuzumab arm was continued to examine the efficacy and safety of the anthracycline-free regimen. Methods Women with human epidermal growth factor receptor-2-positive, operable and primary breast cancer were randomized to receive 5-fluorouracil, epirubicin and cyclophosphamide (four cycles) followed by docetaxel, cyclophosphamide and trastuzumab (four cycles), or docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide, or docetaxel, cyclophosphamide and trastuzumab (six cycles). After the protocol amendment, patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm alone. The primary endpoint was a pathological complete response. Results In total, 103 patients were enrolled between September 2009 and September 2011: 21, 22 and 24 patients in the 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel, cyclophosphamide and trastuzumab; docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide and docetaxel, cyclophosphamide and trastuzumab arms, respectively, and 36 patients in the docetaxel, cyclophosphamide and trastuzumab arm after the protocol amendment. In total, 60 patients were allocated to the docetaxel, cyclophosphamide and trastuzumab arm, in which the pathological complete response rate was 45.8%, and disease-free survival at 3 years was 96.6%. Patients with stage I or IIA in the docetaxel, cyclophosphamide and trastuzumab arm showed good disease-free survival (100% at 3 years). The comparison of efficacy among the three arms was statistically underpowered. Left ventricular ejection fraction decreased significantly after 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel–docetaxel, cyclophosphamide and trastuzumab (P = 0.017), but not after docetaxel, cyclophosphamide and trastuzumab followed by 5-fluorouracil, epirubicin and cyclophosphamide or docetaxel, cyclophosphamide and trastuzumab. Conclusions The pathological complete response rate for docetaxel, cyclophosphamide and trastuzumab was similar to previous reports of anthracycline-containing regimens. Docetaxel, cyclophosphamide and trastuzumab might be an option for primary systemic therapy in human epidermal growth factor receptor-2-positive early breast cancer. A larger confirmatory study is necessary.

scholarly journals High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller

2009 ◽  
Vol 27 (34) ◽  
pp. 5700-5706 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Jennifer K. Litton ◽  
Kristine R. Broglio ◽  
Funda Meric-Bernstam ◽  
Ronjay Rakkhit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Distant Recurrence ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Node Negative ◽  
Epidermal Growth

Purpose To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) –positive breast cancer. Methods We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence–free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Results Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor–positive tumors. Conclusion Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

scholarly journals Management of Early-Stage Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

2021 ◽  
Vol 17 (6) ◽  
pp. 320-330 ◽  
Author(s):  
Sonia Pernas ◽  
Sara M. Tolaney
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Epidermal Growth ◽  
Positive Breast Cancer

The addition of trastuzumab to chemotherapy dramatically improved the prognosis of early-stage human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, 15%-31% of patients still develop disease recurrence, on the basis of long-term follow-up of adjuvant pivotal trials. A better understanding of tumor biology has led to the development of optimized anti-HER2 drugs and add-on strategies to further improve survival outcomes. In the neoadjuvant setting, dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy has increased the rate of pathologic complete response, a surrogate marker of improved long-term outcome; yet, in the adjuvant setting, it has led to small benefits in invasive disease-free survival. Extended adjuvant therapy with the irreversible pan-HER2 inhibitor neratinib is an option for selected patients with HER2-positive and estrogen receptor–positive disease who have received neoadjuvant or adjuvant chemotherapy plus trastuzumab. Additionally, the use of the antibody-drug conjugate trastuzumab-emtansine has led to a significant improvement in invasive disease-free survival for patients with residual disease following neoadjuvant therapy and has taught us the importance of using preoperative therapy to adapt adjuvant treatment. Nevertheless, recurrences in the brain remain an important caveat, and not all patients benefit to the same extent from anti-HER2 therapies. Biologic heterogeneity within HER2-positive disease may modulate treatment response and prognosis. De-escalating treatment strategies to avoid unnecessary treatments and toxicities, without compromising outcomes, have become a crucial focus of research. To stratify patient risks and optimize treatment selection, other biomarkers including intrinsic subtype, level of HER2, and tumor-infiltrating lymphocytes should be further evaluated. We discuss the latest evidence on the current approach of early-stage, HER2-positive breast cancer and present future perspectives on its management.

scholarly journals Optimal time for adjuvant therapy initiation in breast cancer patients: A single center experience

2018 ◽  
Vol 71 (11-12) ◽  
pp. 394-403
Author(s):  
Bojana Vranjkovic ◽  
Dragana Petrovic ◽  
Jelena Radic ◽  
Maja Popovic ◽  
Kolarov Bjelobrk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Free Survival ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth ◽  
Disease Free

Introduction. This retrospective study evaluates the association between the time of chemotherapy initiation and disease free survival in regard to breast cancer subtypes and stage at diagnosis. Material and Methods. The study included a total of 1075 breast cancer patients, stages I - III, treated at Oncology Institute of Vojvodina, Serbia (from 2010 to 2012; n = 617). The gathered data included prognostic factors used in everyday practice. Patients were divided into three groups according to the interval between surgery and chemotherapy (? 30, 31 - 60, ? 61 days). Disease free survival was calculated. Results. Among the 617 patients, the 5-year disease free survival estimate was similar: 81.5%, 81.0%, 84.6% (log-rank test, p = 0.728) regarding the time of adjuvant chemotherapy initiation: ? 30 days, 31 - 60, and ? 61 days, respectively. The study showed that 85% of our breast cancer patients started adjuvant chemotherapy within 3 months after definitive surgery. In multivariate analysis, independent prognostic factors for disease free survival were nodal status and tumor size. The 5-year disease free survival estimate was 85.8% (p = 0.001) for patients with luminal- A subtype (Estrogen +, Progesterone high, human epidermal growth factor receptor 2-, Ki-67 < 20%) with a median follow-up of 62,7 months; for patients with luminal-B (Luminal B (human epidermal growth factor receptor 2 -) Estrogen +, human epidermal growth factor receptor 2-, either Ki-67 high or Progesterone low, Luminal B (human epidermal growth factor receptor +) Estrogen +, human epidermal growth factor receptor 2 +, any Ki-67, any Progesterone) 78.3% (p = 0.534) with a median follow-up of 55.9 months; for patients with triple negative breast cancer it was 73.4% with a median follow-up of 58,1 months, and for patients with human epidermal growth factor receptor 2+ it was 77.1% (p = 0.448) with a median follow-up of 55.5 months. Conclusion. Early initiation of adjuvant chemotherapy is particularly important in patients with advanced- stage breast cancer at diagnosis, and those with trastuzumab- treated triple-negative breast cancer and human epidermal growth factor receptor 2-positive tumors.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Disease-free survival pattern in breast cancer patients in India treated in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12030-e12030 ◽  
Author(s):  
Basavalinga S. Ajaikumar ◽  
Kodaganur Srinivasachar Gopinath ◽  
B S Srinath ◽  
Ramesh Bilimagga S ◽  
Nalini K Rao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Distant Failure ◽  
Her 2 ◽  
Disease Free

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.

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