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 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 Primary Systemic Therapy for HER2/Neu-Positive Operable Breast Cancer Increases the Number of Breast-Conserving Surgery and Disease-Free Survival: Retrospective Cohort Analysis at Single Institution

2021 ◽  
Vol 07 (02) ◽  
pp. 089-095
Author(s):  
Yohana Azhar ◽  
Hasrayat Agustina ◽  
Bethy S Hernowo
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Conserving Surgery ◽  
Breast Cancer Surgery ◽  
Primary Systemic Therapy ◽  
Free Survival ◽  
Hormonal Receptor ◽  
Sequential Regimen ◽  
Disease Free

Abstract Objective The aim of this study was to evaluate the efficacy and cardiotoxicity profile, and to reduce the extend of breast cancer surgery in primary systemic therapy (PST) HER2/neu–positive operable breast cancer patients. Materials and Methods A total of 152 patients diagnosed from 2010 to 2015 were included in the study. The PST consisted of a sequential regimen of taxanes and anthracyclines plus trastuzumab. The clinical and pathological responses and the type of breast cancer surgery were evaluated and correlated with clinical and biological factors. The cardiotoxicity profile and long-term benefits were analyzed. Results The median patient age was 47 (37–67) years, with T2 and T3 67 (44.1%) and 85 (55.9%), respectively. Axillary lymph node breast cancer at diagnosis N0 was 104 (68.4%) and N1 and N2 were 28.9% and 2.6%, respectively. A total of 95.7% of patients had nonspecific type of breast cancer, 67% of tumors were hormonal receptor–negative, 75.5% were grade III, 100% Ki67 > 20%, and 90% of tumors were confirmed to be HER2/neu–positive through immunohistochemistry. Following PST, pathological complete response (pCR) rate was achieved in 44.7% evaluable patients. The pCR rate was higher in HR-negative (93.1% vs. 6.9%) cancer and in grade III (86.2%) than in grade I and II (13.8%) cancer; only 75.5% of complete response (CR) on ultrasound and magnetic resonance imaging were also CR on pathology results. Breast conserving surgery was performed in 41.4%. Regarding type of chemotherapy, there were no significant differences between chemotherapy with anthracycline backbone or taxanes to achieved pathological complete response. Despite that, we were unable to demonstrate an association between pCR and better DFS with p = 0.096; HR 5.7 95.0% CI (0.73–45.52). Patients who are hormonal receptor positive tend to have lower disease-free survival (DFS) than those who are hormonal receptor negative; HR = 6.34, 95.0% CI (1.54–26.00) and p = 0.010. Five years DFS was higher for those who achieved pCR compare with those who did not. Even in this research we failed to show it is statistically significant. Conclusion A sequential regimen of taxanes and anthracyclines plus trastuzumab was effective with high pCR rates and increases the possibility to do breast conservation surgery and had tolerable cardiotoxicity profile.

scholarly journals Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis

BMJ ◽  
2021 ◽  
pp. e066381
Author(s):  
Fabio Conforti ◽  
Laura Pala ◽  
Isabella Sala ◽  
Chiara Oriecuia ◽  
Tommaso De Pas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Relative Risk ◽  
Pathological Complete Response ◽  
Early Stage ◽  
Disease Free Survival ◽  
Complete Response ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Disease Free

Abstract Objective To evaluate pathological complete response as a surrogate endpoint for disease-free survival and overall survival in regulatory neoadjuvant trials of early stage breast cancer. Design Systematic review and meta-analysis. Data sources Medline, Embase, and Scopus to 1 December 2020. Eligibility criteria for study selection Randomised clinical trials that tested neoadjuvant chemotherapy given alone or combined with other treatments, including anti-human epidermal growth factor 2 (anti-HER2) drugs, targeted treatments, antivascular agents, bisphosphonates, and immune checkpoint inhibitors. Data extraction and synthesis Trial level associations between the surrogate endpoint pathological complete response and disease-free survival and overall survival. Methods A weighted regression analysis was performed on log transformed treatment effect estimates (hazard ratio for disease-free survival and overall survival and relative risk for pathological complete response), and the coefficient of determination (R 2 ) was used to quantify the association. The secondary objective was to explore heterogeneity of results in preplanned subgroups analysis, stratifying trials according treatment type in the experimental arm, definition used for pathological complete response (breast and lymph nodes v breast only), and biological features of the disease (HER2 positive or triple negative breast cancer). The surrogate threshold effect was also evaluated, indicating the minimum value of the relative risk for pathological complete response necessary to confidently predict a non-null effect on hazard ratio for disease-free survival or overall survival. Results 54 randomised clinical trials comprising a total of 32 611 patients were included in the analysis. A weak association was observed between the log(relative risk) for pathological complete response and log(hazard ratio) for both disease-free survival (R 2 =0.14, 95% confidence interval 0.00 to 0.29) and overall survival (R 2 =0.08, 0.00 to 0.22). Similar results were found across all subgroups evaluated, independently of the definition used for pathological complete response, treatment type in the experimental arm, and biological features of the disease. The surrogate threshold effect was 5.19 for disease-free survival but was not estimable for overall survival. Consistent results were confirmed in three sensitivity analyses: excluding small trials (<200 patients enrolled), excluding trials with short median follow-up (<24 months), and replacing the relative risk for pathological complete response with the absolute difference of pathological complete response rates between treatment arms. Conclusion A lack of surrogacy of pathological complete response was identified at trial level for both disease-free survival and overall survival. The findings suggest that pathological complete response should not be used as primary endpoint in regulatory neoadjuvant trials of early stage breast cancer.

Pathological complete response rates in HER2 amplified breast cancers based on levels of HER2 amplification.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12632-e12632
Author(s):  
Ina Patel ◽  
Yasmeen Hashimie ◽  
James Hall ◽  
Ashwini Bhat
Keyword(s):  
Breast Cancer ◽  
Pathological Complete Response ◽  
Disease Free Survival ◽  
Response Rates ◽  
Complete Response ◽  
Response To Therapy ◽  
P Value ◽  
Her2 Amplification ◽  
Free Survival ◽  
Disease Free

e12632 Background: Untreated HER2 (Human Epidermal Growth Factor) amplified breast cancer has poorer prognosis, compared to those with HER2 negative status with shorter time to relapse and increased incidence of metastases and higher mortality. Both Trastuzumab and Pertuzumab (humanized monoclonal antibodies against HER2) have shown to improve PCR (Pathological Complete Response) rates when used in the neoadjuvant setting. However, whether the quantitative level of HER2 amplification affects PCR rates or disease-free survival/overall survival has not been well studied. If the level of HER2 amplification correlates with PCR rates, this could be a tool for clinicians to use as a predictive marker for response to therapy. Methods: This is a retrospective chart review of community oncology clinic patients with HER2 amplified breast cancer Stage I-III to evaluate the rates of PCR after HER2 targeted neo-adjuvant therapy categorized by HER2 CISH (Chromogenic in situ hybridization) amplification and stratified based on levels of amplification of < 3, 3 to 5, or > 5. Pathology reports were reviewed for report of PCR. Inclusion criteria was women age 19 to 90, HER2 positive biopsy proven breast cancer, Stage I-III, patients treated with neoadjuvant chemotherapy, adequate renal function, and left ventricular ejection fraction within normal range. Exclusion criteria was pregnancy, metastatic disease, history of other malignancies, and impaired renal or cardiac function. Results: The data consisted of 36 unique patients, 25% of whom had a HER2 below 3, 22.2% had a HER2 between 3 and 5, and 52.8% had a HER2 value > 5. There was found to be a statistically significant association between the level of HER2 amplification and PCR rates with increased amplification of HER2 relates with increased PCR rates (p value < 0.0176). Both three-year disease-free survival and three-year overall response rates were not statistically significantly associated with HER2 category (p value -0.2691 and 0.4692 respectively). Conclusions: The information from this study may introduce a future systematic approach to further risk stratify patients based upon their quantitative HER2 amplification level to help predict response to therapy. We have noted that a level of HER2 amplification > 5 led to significant association with PCR compared to < 3 and 3-5 values.

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.

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

Sign in / Sign up

Export Citation Format

Share Document