scholarly journals Optimal Duration of Neoadjuvant Taxane and Carboplatin Combined With Anti-HER2 Targeted Therapy for HER2-Positive Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yifan Xie ◽  
Siyu Wu ◽  
Ying Zhang ◽  
Jianwei Li ◽  
Miao Mo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Multivariable Analysis ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Significant Difference ◽  
Cycle Group ◽  
Positive Breast Cancer

BackgroundTaxane, carboplatin and trastuzumab (TCH) is an effective neoadjuvant regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer with high pathologic complete response (pCR) rate. The KATHERINE trial changes the outlook for high-risk HER2-positive breast cancer, which suggests that escalation treatment for patients with residual disease after neoadjuvant anti-HER2 therapy may improve survival. The major objective of this study was to investigate the fewest cycles of neoadjuvant TCH therapy needed to screen out non-pCR patients.MethodsThis retrospective study included patients with HER2-positive breast cancer who received either four or six cycles of TCH preoperatively at Fudan University Shanghai Cancer Center between 2008 and 2019. The pCR status was evaluated, and relevant factors associated with pCR were identified using univariate and multivariable analyses. The pathological results of core needle biopsy (CNB) in the breast tumor after two cycles of neoadjuvant chemotherapy were also collected. Kaplan-Meier curve was used to estimate the event-free survival (EFS).ResultsOf 758 eligible patients, 303 were included and analyzed in the four-cycle group and 455 in the six-cycle group. There was no significant difference between the two groups in terms of the pCR rate (46.5% [95% CI 40.9% - 52.2%] in the four-cycle group and 49.9% [95% CI 45.3% - 54.5%] in the six-cycle group, p = 0.365) or the four-year EFS (90.8% in four-cycle group and 93.8% in six-cycle group; p = 0.264). Multivariable analysis indicated that a negative hormone receptor status and the weekly paclitaxel were independent factors for predicting pCR. After adjusting for factors in the multivariable analysis, there was still no significant difference between four and six cycles of neoadjuvant TCH (OR = 1.252, 95% CI 0.904 - 1.733, p = 0.176). Furthermore, 17.9% patients with invasive carcinoma on CNB after two cycles of TCH ultimately achieved pCR in the breast after the completion of neoadjuvant treatment.ConclusionFour cycles of taxane/carboplatin-based neoadjuvant anti-HER2 therapy may be applied as an optimal treatment duration for screening high-risk HER2-positive breast cancer patients for escalation treatment. Further prospective study is warranted.

scholarly journals Neoadjuvant zoledronic acid for HER2-positive breast cancer: the Zo-NAnTax trial

2019 ◽  
Vol 11 ◽  
pp. 175883591985397 ◽  
Author(s):  
Susanne Crocamo ◽  
Renata Binato ◽  
Bruno de Paula ◽  
Giselle Vignal ◽  
Lídia Magalhães ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Mevalonate Pathway ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Grade 3 ◽  
Positive Breast Cancer

Background: Preclinical evidence suggests that zoledronic acid (ZOL) works synergistically with chemotherapy by enhancing anti-tumor activity. ZOL blocks the mevalonate pathway and may indirectly interact with human epidermal growth factor receptor 2 (HER2) pathway activation. The clinical efficacy and biological rationale of chemotherapy plus anti-HER2 therapy and ZOL as a part of neoadjuvant therapy has not been previously tested. Patients and methods: We conducted a phase II clinical trial to evaluate the efficacy and safety of ZOL as part of a neoadjuvant treatment in patients with HER2-positive breast cancer (BC). The protocol consisted of four cycles of doxorubicin/cyclophosphamide with ZOL, followed by four cycles of docetaxel with trastuzumab and ZOL prior to surgery. The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints were safety and the identification of clinicopathological characteristics associated with pCR. Results: A total of 71 patients with stage IIA to IIIB BC were included, with 60 eligible for the safety assessment and 58 for the efficacy analysis. Overall, the pCR rate was 42%, with higher rates in hormone receptor (HR)-positive tumors (40%), which contrasts with the results of pivotal trials. The most commonly observed grade 3 and 4 events were febrile neutropenia (grade 3, 20%; grade 4, 3%) and diarrhea (grade 3, 12%). Conclusions: The addition of ZOL as a repositioning drug in neoadjuvant treatment was an effective and well-tolerated therapy. This drug combination might overcome endocrine and anti-HER2 resistance. The higher pCR rates in the HR-positive subgroup deserve further translational investigation.

scholarly journals TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

2019 ◽  
Vol 37 (9) ◽  
pp. 714-722 ◽  
Author(s):  
Roisin M. Connolly ◽  
Jeffrey P. Leal ◽  
Lilja Solnes ◽  
Chiung-Yu Huang ◽  
Ashley Carpenter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Predictive Value ◽  
Pathologic Complete Response ◽  
Area Under The Curve ◽  
Complete Response ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positron Emission ◽  
Significant Difference ◽  
Positive Breast Cancer

PURPOSE Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)–positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS Patients with stage II/III, estrogen receptor–negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION Early changes in SULmax predict response to four cycles of PT in estrogen receptor–negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

Neoadjuvant Treatment With Trastuzumab in HER2-Positive Breast Cancer: Results From the GeparQuattro Study

2010 ◽  
Vol 28 (12) ◽  
pp. 2024-2031 ◽  
Author(s):  
Michael Untch ◽  
Mahdi Rezai ◽  
Sibylle Loibl ◽  
Peter A. Fasching ◽  
Jens Huober ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Reference Group ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Breast Conservation ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Purpose Trastuzumab, a humanized antibody against the human epidermal growth factor receptor type 2 (HER2), has shown high efficacy in breast cancer. We prospectively investigated its efficacy given simultaneously with anthracycline-taxane–based neoadjuvant chemotherapy. Patients and Methods Patients with operable or locally advanced, HER2-positive tumors were treated preoperatively with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel with or without capecitabine (EC-T[X]) and trastuzumab 6 mg/kg (with a loading dose of 8 mg/kg) every 3 weeks during all chemotherapy cycles. Patients with HER2-negative tumors treated in the same study with the same chemotherapy but without trastuzumab were used as a reference group. Results Of 1,509 participants, 445 had HER2-positive tumors treated with trastuzumab and chemotherapy. Pathologic complete response (pCR; defined as no invasive or in situ residual tumors in the breast) rate was 31.7%, which was 16% higher than that in the reference group (15.7%). HER2-positive patients without response to the first four cycles of EC showed an unexpectedly high pCR rate of 16.6% (3.3% in the reference group). Breast conservation rate was 63.1% and comparable to that of the reference group (64.7%). EC-T(X) plus trastuzumab was associated with more febrile neutropenia and conjunctivitis, but with a comparable short-term cardiac toxicity profile as the reference group. Conclusion This trial confirms that combining trastuzumab with anthracycline-taxane–based neoadjuvant chemotherapy results in a high pCR rate without clinically relevant early toxicity. Combination of chemotherapy with trastuzumab should be considered when neoadjuvant treatment is given to patients with HER2-positive breast cancer.

scholarly journals Immune Checkpoint Blockade in HER2-Positive Breast Cancer: What Role in Early Disease Setting?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1655
Author(s):  
Cinzia Solinas ◽  
Debora Fumagalli ◽  
Maria Vittoria Dieci
Keyword(s):  
Breast Cancer ◽  
Immune Checkpoint ◽  
Neoadjuvant Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Current Evidence ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

The present commentary synthesizes the current evidence on the role of the immune response in HER2-positive breast cancer. It points out the strengths and weaknesses of the findings observed so far, particularly in the early setting, including the clinical significance of scoring tumor-infiltrating lymphocytes. A figure proposing research hypotheses for the implementation of immune checkpoint blockade use for patient candidates to neoadjuvant treatment is presented.

scholarly journals Neoadjuvant Pertuzumab plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2 Positive Breast Cancer: Real-World Data from a National Institute of Oncology in Poland.

2022 ◽  
Author(s):  
Agnieszka Irena Jagiełło-Gruszfeld ◽  
Magdalena Rosinska ◽  
Malgorzata Meluch ◽  
Katarzyna Pogoda ◽  
Anna Niwińska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Her2 Positive ◽  
Real World Data ◽  
Cancer Subtypes ◽  
Cancer Management ◽  
Her2 Positive Breast Cancer ◽  
Neoadjuvant Systemic Therapy ◽  
Positive Breast Cancer

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

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