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.

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.

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.

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.

Changing pattern of recurrences in patients with early HER2-positive breast cancer receiving neoadjuvant chemotherapy in the era of dual anti-HER2 therapy

2019 ◽  
Vol 95 (1121) ◽  
pp. 155-161 ◽  
Author(s):  
Joanne W Chiu ◽  
Roland Leung ◽  
Vikki Tang ◽  
Wai Yin Cheuk ◽  
Jessica Lo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Surveillance ◽  
Breast Conservation ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Her2 Positive ◽  
Tertiary Referral Centre ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

BackgroundOver the last 10 years, there has been a major treatment revolution for early human epidermal growth factor receptor 2 (HER2)–positive breast cancer. We aimed to explore the outcome of different neoadjuvant chemotherapy in a tertiary breast cancer centre with early HER2-positive breast cancer as well as factors associated with pathological complete response (pCR) and recurrence-free survival (RFS). The pattern of recurrence was also studied.MethodsThis retrospective study analysed the outcome of neoadjuvant chemotherapy during the period 2005 to 2016 in a tertiary referral centre in Hong Kong. Patients were divided into three groups according to the neoadjuvant chemotherapy they received: chemotherapy only (Chemo), chemotherapy plus trastuzumab (Chemo-H) and chemotherapy plus double anti-HER2 therapy (Chemo-DH).ResultsThere were 226 cases analysed during the study period. The rate of pCR was 5%, 26% and 60% in Chemo, Chemo-H and Chemo-DH groups, respectively (Chemo vs pooled Chemo-H/DH: p<0.0001; Chemo-H vs Chemo-DH: p<0.0001). This was accompanied by a trend of increased rate of breast conservation therapy in Chemo-DH cohort (p=0.046). Use of double anti-HER2 therapy, older age (>50 years) and hormone receptor negativity were associated with more pCR. pCR was associated with better RFS. Among those with recurrence, the proportion of patients with brain as the only site of recurrence increased remarkably with more efficacious anti-HER2 treatment (0% in Chemo, 8% in Chemo-H, 67% in Chemo-DH).ConclusionpCR remains an important predictive factor for improved RFS. In the era of dual anti-HER2 neoadjuvant therapy, brain-only recurrence poses a challenge to disease surveillance and treatment.

Clinical utility of SERUM extracelullar domain of HER2 receptor (ECD) in HER2-positive breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12086-e12086
Author(s):  
Ariadna Gasol Cudós ◽  
Serafin Morales Murillo ◽  
Joel Veas Rodriguez ◽  
Carles Canosa Morales ◽  
Jordi Melé Olivé ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Positive Breast Cancer

e12086 Background: Although ECD expression was validated as tumor marker years ago, it is not used in daily clinical practice even if a prognostic value was demonstrated in some trials. Methods: In our single institution, during January 2013-2019, ECD was analyzed in a series of HER2 positive breast cancer patients; 71 in early or locally-advanced and 45 in metastatic setting. Results: In the metastatic cohort, median ECD expression was of 28 ng/ml (6,5-350), thus 10 (22%) patients had lower levels than threshold of 15ng/ml. No correlation was found between ECD expression and other clinicopathological variables. No association was found with overall survival however in patients with metastases at diagnosis higher ECD expression was correlated with a short overall survival (25 vs 54 months). Higher levels of ECD decreased according to good response to treatment. Median ECD expression was of 12ng/ml (3,6-97) in non-metastatic setting, however only 11 (15%) patients had elevated levels ( > 15ng/ml). Estrogen receptor and ki67 expression were not correlated with ECD levels. Median ECD expression in tumors > 5cm was 21,87 ng/ml versus 12ng/ml in smaller tumors (p = 0,006); in nodal involvement median ECD was 16,77 ng/ml versus 12,05 without affectation (p = 0,09). Patients with ECD higher than 10 ng/ml had a 55% pathologic complete response (pCR) versus 25% if less than 10ng/ml (OR 3.68, p = 0.027). Interestingly, none of tumors > 5cm and ECD < 10ng/ml achieved a pCR. Conclusions: Higher levels of ECD were observed in the metastatic setting and their decreased levels during treatment was correlated with response. In early and locally-advanced setting higher levels were found in larger tumors; and also these tumors had better response than lower levels of ECD. ECD could be used as a monitoring tool in the metastatic scenario and as a predictive factor of response in the neoadjuvant setting, specifically in tumors > 5cm.

scholarly journals Lapatinib, trastuzumab or the combination added to neoadjuvant chemotherapy for breast cancer

2016 ◽  
Vol 11 (4) ◽  
pp. 863
Author(s):  
Quan Liang ◽  
Qiang Fu ◽  
Wei Li ◽  
Jiacong You ◽  
Zhanchao Zhao
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Complete Response Rate ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Cochrane Library ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

<p>The aim of this study was to compare the efficacy and safety of trastuzumab versus the combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy for HER2 positive breast cancer. PubMed, MEDLINE, The Cochrane Library, Web of Science and nearly 5 years of the important international conference on oncology records were searched for randomized clinical trials that compared lapatinib plus trastuzumab and neoadjuvant chemotherapy (NAC) with trastuzumab in combination with NAC and that included pathologic complete response rate as the primary outcome. Finally, 6 clinical randomized controlled trials were included. Meta-analysis shows that pathological complete response rate was significantly increased in trastu-zumab plus lapatinib group than single use trastuzumab group (53.4%, 40.4%, RR = 1.75, 95% CI 1.38 ~ 2.23, p&lt;0.001). In conclusion, the combination of trastuzumab and lapatinib added to neoadjuvant chemotherapy in HER2 positive breast cancer is more effective.</p><p> </p>

The impact of hormone receptor status on pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy with or without trastuzumab

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 533-533
Author(s):  
F. Peintinger ◽  
A. Buzdar ◽  
H. Kuerer ◽  
A. Gonzalez-Angulo ◽  
C. Hatzis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Pathologic Complete Response ◽  
Pathologic Response ◽  
Weekly Paclitaxel ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
The Impact ◽  
Positive Breast Cancer

533 Background: The aim of this study was to compare the extent of pathologic response in HER2-positive patients treated with standard neoadjuvant chemotherapy with or without trastuzumab according to hormone receptor (HR) status. Methods: The study included 199 patients with HER2-positive disease treated in clinical trials of neoadjuvant chemotherapy. Eighty-nine patients treated with 3- weekly paclitaxel and concurrent trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) were compared with 110 patients treated with weekly or 3-weekly paclitaxel followed by FEC or FAC. Residual cancer burden (RCB), a measurement of residual disease (RD) from pathologic review of the primary tumor and lymph nodes, was classified as pathologic complete response (pCR), RCB-I (near-pCR, minimal RD), RCB-II (moderate RD), or RCB-III (extensive RD). RCB was compared between treatment groups according to HR status. Results: In HR-negative patients, similar pCR rates were achieved with weekly T/FAC as with 3-weekly T/FEC and trastuzumab (61% and 65%, respectively). However, in HR-positive patients, higher pCR rates were achieved with 3-weekly T/FEC and trastuzumab (47%) than with the weekly T/FAC (25%; p=0.04) or 3-weekly T/FAC (19%; p=0.01) ( Table 1 ). Near pCR (RCB-I) was slightly higher in HR-positive (26%) than in HR-negative patients treated with 3-weekly T/FEC and trastuzumab (11%; p=0.07). Conclusions: Patients with HR- negative/HER2-positive breast cancer had similar pathologic response rates from addition of trastuzumab to 3-weekly T/FEC or from weekly T/FAC chemotherapy. Patients with HR-positive/HER2-positive breast cancer obtained significant benefit from addition of trastuzumab to 3- weekly T/FEC, compared to 3-weekly T/FAC or weekly T/FAC. The combination of weekly T/FEC with trastuzumab as neoadjuvant chemotherapy should be evaluated. [Table: see text] [Table: see text]

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