Dose-dense docetaxel, carboplatinum and trastuzumab (ddTCH) as neoadjuvant therapy for human epidermal receptor 2 (HER2) positive breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11003-11003 ◽  
Author(s):  
H. S. Han ◽  
P. Doliny ◽  
M. Blaya ◽  
S. Gluck ◽  
J. Slingerland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Pathologic Complete Response ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Grade Ii ◽  
Her 2 ◽  
Dose Dense ◽  
Grade Iii ◽  
Positive Breast Cancer

11003 Background: Docetaxel, cisplatin, and trastuzumab given every 21 days in Her 2-postitive breast cancer demonstrates a pathologic complete response (pCR) rate of 23%. Decreasing the interval between doses of chemotherapy has lead to improvement in survival in the adjuvant setting. In one study dose dense chemotherapy improved response only in patients whose tumors overexpressed her-2. We conducted a phase II trial to evaluate the efficacy and safety of neoadjuvant dose-dense TCH for HER 2-positive breast cancer. Methods: Patients with T2–4 N0–3 M0 HER-2 positive (by FISH) breast cancers were eligible. Neoadjuvant therapy consisted of carboplatinum (AUC 6) Day 1,15,29,43, docetaxel (75mg/m2) Day 1,15,29, 43 and weekly trastuzumab for 10 weeks 4mg/kg Day 1 then 2mg/kg Day 8,15,22,29,36,43,50,57,64, Pegfilgastrim Day 2,16,30,44. The primary end point was the rate of pCR. Results: Twenty patients are evaluable for response. The median age was 51.5 years (range 29–73). Mean tumor size was 5.6 cm. Patients had stage IIA (30%), IIB (15%), IIIA (45%), IIIB (5%), and IIIC (5%). Estrogen receptors were positive in 36% of tumors. No grade 4 or 5 toxicity occurred. The most frequent toxicity was hand-foot syndrome (Grade I 15%, Grade II 10%, Grade III 15%). Neutropenia occurred in 5 patients (Grade II 10%, Grade III 15%) There were no episodes of febrile neutropenia or hospitalizations. Grade I cardiotoxicity was seen in 30%. The rate of pCR was 40% in the breast and 35% in both breast and axilla. 16/20 patients (80%) had pathologically negative lymph nodes. Conclusions: Changing the scheduling of TCH from every 21 days to every 14 days improves the pCR rate from 23 to 40%. The regimen was well tolerated. No significant financial relationships to disclose.

Comparison of serum HER-2/neu between trastuzumab-based regimen and anthyracycline-based regimen during neoadjuvant chemotherapy in advanced primary breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11582-e11582
Author(s):  
J. Lee ◽  
W. Min ◽  
S. Kim ◽  
B. Son
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Ductal Carcinoma ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Breast Cancers ◽  
Maximal Diameter ◽  
Her 2 ◽  
Positive Breast Cancer

e11582 Background: Serum Her-2/neu has been known as molecular surrogating marker of predicting treatment response in Her-2 positive breast cancer. We compare the change of serum Her-2/neu during neoadjuvant chemotherapy between trastuzumab(H) and anthyracyline(A) based treatment. Methods: All breast cancers were tested by immunohistochemical stain and FISH for Her-2/neu before treatment. Serum Her-2/neu was twice measured by Chemiluminescence immunoassay(ADVIA centaurTMsystem) before neoadjuvant chemotherapy and before operation. The cutoff value was 10.2 mg/ml according to previous study. Pathologic complete response (pCR) was considered as no residual tumor or remnant ductal carcinoma in situ, partial response (PR) was less than 50% decrease in maximal diameter in pathologic tumor size. Results: Serum Her-2/neu of trastuzumab group was more decreased than of anthyracyline group (H; 12.9 ± 14.5 ng/mL vs. A; 2.2 ± 1.2 ng/mL, p=0.024). In trastuzumab group, pCR was relatively correlated with decrease of serum Her-2/neu (PR: 0.8 ± 0.84 ng/ml vs. pCR: 21.1 ± 13.2 ng/ml, p=0.08). Conclusions: A decrease in serum Her-2/neu levels during treatment was associated with pathologic response in patients receiving neoadjuvant chemotherapy, particularly, trastuzumab-based regimen. Serum Her-2/neu levels may serve to monitoring neoadjuvant therapy in Her-2/neu positive breast cancer. No significant financial relationships to disclose.

scholarly journals Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes

JAMA Oncology ◽  
2016 ◽  
Vol 2 (6) ◽  
pp. 751 ◽  
Author(s):  
Kristine R. Broglio ◽  
Melanie Quintana ◽  
Margaret Foster ◽  
Melissa Olinger ◽  
Anna McGlothlin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Long Term Outcomes ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 342 ◽  
Author(s):  
Babak Nami ◽  
Hamid Maadi ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Her 2 ◽  
Available Information ◽  
Positive Breast Cancer

Human epidermal growth factor receptor (HER) 2 (HER2) is overexpressed in 20–30% of breast cancers. HER2 is a preferred target for treating HER2-positive breast cancer. Trastuzumab and pertuzumab are two HER2-targeted monoclonal antibodies approved by the Food and Drug Administration (FDA) to use as adjuvant therapy in combination with docetaxel to treat metastatic HER2-positive breast cancer. Adding the monoclonal antibodies to treatment regimen has changed the paradigm for treatment of HER2-positive breast cancer. Despite improving outcomes, the percentage of the patients who benefit from the treatment is still low. Continued research and development of novel agents and strategies of drug combinations is needed. A thorough understanding of the molecular mechanisms underlying the action and synergism of trastuzumab and pertuzumab is essential for moving forward to achieve high efficacy in treating HER2-positive breast cancer. This review examined and analyzed findings and hypotheses regarding the action and synergism of trastuzumab and pertuzumab and proposed a model of synergism based on available information.

scholarly journals Efficacy and safety of neoadjuvant therapy for HER2-positive early breast cancer: a network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Jie Zhang ◽  
Yushuai Yu ◽  
Yuxiang Lin ◽  
Shaohong Kang ◽  
Xinyin Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Combination Chemotherapy ◽  
Target Therapy ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Single Target ◽  
Dual Target ◽  
Better Than ◽  
Positive Breast Cancer

Aims: Currently, there are many approaches available for neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer that improve therapeutic efficacy but are also controversial. We conducted a two-step Bayesian network meta-analysis (NMA) to compare odds ratios (ORs) for pathologic complete response (PCR) and safety endpoints. Methods: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and online abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium were searched comprehensively and systematically. Phase II/III randomised clinical trials for targeted therapy in at least one arm were included. Results: A total of 9779 published manuscripts were identified, and 36 studies including 10,379 patients were finally included in our analysis. The NMA of PCR showed that dual-target therapy is better than single-target therapy and combination chemotherapy is better than monochemotherapy. However, anthracycline did not bring extra benefits, whether combined with dual-target therapy or single-target therapy. On the other hand, the addition of endocrine therapy in the HER2-positive, hormone receptor (HR)-positive subgroup might have additional beneficial effects but without significant statistical difference. By performing a conjoint analysis of the PCR rate and safety endpoints, we found that ‘trastuzumab plus pertuzumab’ and ‘T-DM1 containing regimens’ were well balanced in terms of efficacy and toxicity in all target regimens. Conclusion: In summary, trastuzumab plus pertuzumab-based dual-target therapy with combination chemotherapy regimens showed the highest efficacy of all optional regimens. They also achieved the best balance between efficacy and toxicity. As our study showed that anthracycline could be replaced by carboplatin, we strongly recommended TCbHP as the preferred choice for neoadjuvant treatment of HER2-positive breast cancer. We also look forward to the potential value of T-DM1 in improving outcomes, which needs further study in future trials.

scholarly journals UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

2021 ◽  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Needle Biopsy ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

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