HER2 cluster amplification as a factor of an especial sensitivity for anti-HER2 neoadjuvant therapy with biosimilar of trastuzumab in Russian women with breast cancer stage II-III.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12102-e12102
Author(s):  
Irina Vladimirovna Kolyadina ◽  
Olga Gordeeva ◽  
Inna Ganshina ◽  
Larisa Zavalishina ◽  
Yulia Andreeva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Radical Surgery ◽  
Locally Advanced ◽  
Pathologic Response ◽  
Stage Ii ◽  
Cancer Stage ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

e12102 Background: Effect of neoadjuvant chemotherapy (NACT) is extremely important for patients with HER2-positive breast cancer stage II-III as it correlates with long-term outcomes. However, predictive factors for achieving complete pathologic response (pCR) remain unclear. Aim of the study: Assess an impact of clinical, morphological and genetic factors on pCR achievement in patients with HER2-positive breast cancer stage II-III treated by biosimilar of trastuzumab. Methods: We studied treatment results in 73 patients with HER2-positive breast cancer (BC) stage II-III (aged 29-71, median – 51 years), treated with NACT with anti-HER2 therapy and radical surgery in “N.N. Blokhin National Medical Research Center of Oncology” оf the Ministry of Health of the Russian Federation in 2015-2018. After radical surgery pathologic response was assessed. Initially operable tumors were observed in 45,2% patients, locally advanced - in 53,4%. Luminal HER2-positive BC was diagnosed in 41,1%, non-luminal HER2-positive in 58,9%. Ki67 was high (≥ 20%) in 91,5%. NACT included anthracycline and non-antracycline regimens with addition of biosimilar of trastuzumab ± pertuzumab. Radical mastectomy was performed in 78,8% patients, 21,2% had breast-conserving surgery. We studied biopsies obtained before the start of treatment in all women, HER2 amplification was detected by HER2 IQFISH pharmDx (DAKO) kit in accordance with ASCO/CAP 2018 guidelines. In 87,1% HER2+ status was defined as ASCO/CAP 2018 category 1; cluster amplification was detected in 30,1% patients. We analyzed the rate of bpCR и tpCR achievement depending on clinical, pathological data and amplification of HER2. Results: Pathologic complete response in primary tumor (bpCR) was achieved in 57,4%, both in primary tumor and lymph nodes (tpCR) – in 48,9% patients; bpCR achievement depended on age, NACT regimen, addition of pertuzumab and HER2 copy number ( < 0,05). The highest rate of bpCR was noted in women aged 50 and older (71,9%, p = 0,026); in patients received TCH±Р regimen (80,0%, p = 0,045); with addition of pertuzumab (88,9%, p = 0,049); and if cluster amplification was detected (81%, p = 0,013). Cluster amplification was the only one significant predictive factor for achieving tpCR: with cluster amplification - 68,8%, without - 38,7% (p = 0,049). Conclusions: Cluster amplification of HER2 is the most significant factor of especial sensitivity for NACT with biosimilar of trastuzumab in HER2-positive BC stage II-III.

scholarly journals 4CPS-124 Safety and effectiveness of trastuzumab emtansin in locally advanced or metastatic HER2 positive breast cancer

2019 ◽  
Author(s):  
M Mejias Trueba ◽  
R Jiménez Galán ◽  
M Muñoz Burgos ◽  
AB Guisado Gil ◽  
MD Vega Coca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Efficacy and safety of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCH-P) in HER2-positive breast cancer: An Indian experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12619-e12619
Author(s):  
Ajay Gogia ◽  
Shalabh Arora ◽  
SVS Deo ◽  
Sandeep Mathur ◽  
Dayanand Sharma
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Breast Conservation ◽  
Radical Mastectomy ◽  
Stage Ii ◽  
Breast Conservation Surgery ◽  
Secondary Outcome ◽  
Her2 Positive ◽  
Positive Breast Cancer

e12619 Background: Dual targeted therapy with chemotherapy is one of the therapeutic approaches as neoadjuvant treatment in HER2/neu positive breast cancer (BC). However the safety and efficacy data of dual-targeted, chemotherapy regimen (docetaxel, carboplatin, trastuzumab, & pertuzumab [TCH-P] is limited from the Indian subcontinent. Methods: This retrospective study aims to evaluate the efficacy and toxicity of neoadjuvant TCH-P regimen in early, locally advanced, and oligometastatic (OM) HER2-positive BC, at All India Institute of Medical Sciences, New Delhi, India, in between the period 2015-2020. Total 6 cycles of 3-weekly neoadjuvant chemotherapy (NACT) protocol containing docetaxel (75 mg/m2), carboplatin (AUC = 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) and pertuzumab ( 840 mg loading followed by 420 mg) were planned. Subcutaneous peg-filgrastim was prophylactically administered on day 2 of each cycle. The primary outcome was the pathological complete response (pCR), which was defined as an absence of invasive and noninvasive cancer in breast or lymph node and secondary outcome were clinical overall response rate (ORR), rate of breast conservation surgery( BCS) for patients for whom modified radical mastectomy( MRM)was planned and toxicity. Results: Forty-five patients with a median age of 48 years (31-65) were included in this study. The TNM (AJCC-7th edition) stage distribution was stage II, 14 (31.1%); stage III, 29 (64.5%); and stage IV (OM), 2 (4.4%). Clinical node positivity disease was found in 26 (57.8%) cases. Nineteen (42.2%) patients had hormone-positive and 26(57.8%) cases were premenopausal. The clinically ORR and CR were seen in 100% and 60% respectively. Overall pCR rate was observed in 25 (55.6%) patients (70% in stage II). BCS was performed in 23(51.1%) cases. In 12(26.6%) cases, planned MRM was changed to BCS following NACT. Grade 3 and 4 toxicities were diarrhea 7 cases, thrombocytopenia in 6, neutropenia in 4, febrile neutropenia in 1, and anemia in 2 cases. Ten patients required dose modification and interruption. No patient had congestive heart failure or induction death. Conclusions: This is the first study of the non-anthracycline-based neoadjuvant protocol in HER2 positive BC from India. The TCH-P is an effective, safe, and well-tolerated, protocol with a path CR rate of 55.6% and 26.6% BCS conversion rate from planned MRM.

scholarly journals Role of Post-Neoadjuvant therapy with trastuzumab emtansine in HER2-positive breast cancer

2021 ◽  
pp. 68-74
Author(s):  
E. V. Lubennikova ◽  
Ya. V. Vishnevskaya
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Long Term Results ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

Safety of chemoradiotherapy in combination with targeted therapy in patients with locally advanced HER2-positive breast cancer

2017 ◽  
Vol 6 (4) ◽  
pp. 14
Author(s):  
A. S. Belokhvostova ◽  
I. P. Aslanidi ◽  
Yu. A. Ragulin ◽  
T. V. Pekshina ◽  
A. B. Orkina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Locally Advanced ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Neoadjuvant dose-dense docetaxel, carboplatinum, and trastuzumab (ddTCH) chemotherapy for HER2 overexpressing breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11557-e11557 ◽  
Author(s):  
S. Bayraktar ◽  
U. D. Bayraktar ◽  
I. M. Reis ◽  
M. Pegram ◽  
C. Welsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

e11557 Background: Neoadjuvant chemotherapy for locally advanced breast cancer was shown to improve the complete pathologic (pCR) and clinical response (cCR) as well as the disease free survival (DFS). Docetaxel, cisplatin, and trastuzumab given every 21 days in her2-positive breast cancer demonstrated a pCR rate of 23%. The concept of dose dense chemotherapy regimens has attracted much attention and we hypothesized that dose-dense regimen would further improve pCR, cCR and would maintain the safety profile while being a suitable regimen for outpatient administration. Methods: 48 patients with stage II/III HER2-positive breast cancer were prospectively enrolled on a clinical trial of a neoadjuvant regimen consisting of docetaxel 70 mg/m2 on days 1, 15, 29, and 43; carboplatinum at an AUC of 6 on days 1, 15, 29, and 43; trastuzumab 4 mg/kg on day 1 and 2 mg/kg weekly x 10 starting on day 8; peg-filgastrim 6 mg on days 2, 16, 30, and 44. Results: The median age was 50 years (range 30–78). 52% of patients were premenopausal, 63% and 22% were of Hispanic and African descent, respectively. Estrogen receptor was positive in 52% patients and median tumor size was 5 cm at the time of diagnosis. TNM stage distribution at presentation: T1 2%, T2 25%, T3 57%, T4 16%; N0 29%, N1 46%, N2 16%, N3 7%; M0 100%. pCR in breast; axilla; and both breast and axilla was observed in 19 of 44 patients (43.2%; 95% CI 28.3% - 59.0%); in 29 of 44 patients (65.9%; 95% CI 50.1% - 79.5%); and in 16 of 44 patients (36.4%; 95% CI 22.4% - 52.2%), respectively. No grade 4 or 5 toxicity occurred. The most frequent grade 3 toxicities were hand-foot syndrome (7%), neutropenia (4%), nausea/vomiting (2%), and bone pain (2%). Grade 2 cardiotoxicity was seen in 8% of patients and no grade 3 cardiotoxicity was observed. Conclusions: This neoadjuvant regimen was well tolerated and yielded a good pCR rate for this high risk group of patients. No significant financial relationships to disclose.

Neoadjuvant bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: Results from a phase II trial (AVANTHER).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 602-602
Author(s):  
Maria Fernandez Abad ◽  
Isabel Calvo ◽  
Noelia Martinez ◽  
Mercedes Herrero ◽  
Yolanda Quijano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
High Rate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Combination Methods ◽  
Positive Breast Cancer

602 Background: B in combination with T has showed meaningful activity in patients (pts) with metastatic HER2-positive breast cancer. AVANTHER is a Phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. Methods: Pts with centrally-confirmed HER2-positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate of pathological complete response (pCR) in breast and axilla. For all patients, a tissue sample at baseline as well as at surgery was collected for biomarker analyses. Results: A total of 44 pts have been enrolled. Median tumor size: 3.9 cm. Seven (19.4%) pts had stage IIA; 17 (47.2%) stage IIB; 8 (22.2%) stage IIIA and 4 (11.1%) stage IIIB. Twenty-one (58.3%) pts had both positive-hormonal receptors and 10 (27.8%) were hormone receptor negative. Eight (22.2%) pts had sentinel biopsy before NC, being negative in 6 (16.7%) cases. Data from surgery (only from 36 pts): pCR was achieved in 16 (44.4%) pts. Safety and tolerability were good, with rare adverse events of grade ≥3 [1 (2.8%) episode of severe hypertension]. Conclusions: These data show that the combination of P with T and B without an anthracycline for 12 weeks is very effective as NC in HER2 positive breast cancer pts with a high rate of pCR and minimal side effects.

Sign in / Sign up

Export Citation Format

Share Document