Limited efficacy and significant toxicities of lapatinib (Lap) plus chemotherapy as neoadjuvant therapy (NAC) for HER2-positive inflammatory breast cancer (IBC) patients (Pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 594-594 ◽  
Author(s):  
Ricardo H. Alvarez ◽  
Massimo Cristofanilli ◽  
Joe Ensor ◽  
Anthony Lucci ◽  
Wei Tse Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Locally Advanced Breast Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Radical Mastectomy ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Severe Toxicity

594 Background: IBC is a rare disease but the most aggressive form of locally advanced breast cancer with a higher frequency of HER2 neu amplification (HER2+) compared to non-IBC. The EGFR pathways are also important therapeutic targets in IBC. (Zhang D, 2009). Lap is an oral reversible dual kinase inhibitor of epidermal growth factor receptor of EGFR and HER2. Our objective was to determine the efficacy of Lap in combination with paclitaxel as NAC in pts with previously untreated HER2+ IBC. The primary end-point was to determine the rate of pathological complete response (pCR) defined as no residual invasive disease in the breast and the axillary lymph nodes or Residual Cancer Burden (RCB) of 0. (Symmans FW, 2008). The second endpoint was to assess general safety and cardiac toxicity of this combination therapy. Methods: From October 2008 to May 2011, 15 chemo-naïve pts were treated with Lap 1,250 mg/day as a single agent for 2 weeks, followed by 12 weeks of paclitaxel (80 mg/m2 weekly) plus Lap (1,000 mg/day), and finally with 4 cycles of FEC-75 mg/m2 regimen plus Lap (1,000 mg/day) before surgery. Among 12 first pts enrolled, 6 pts had grade 3 diarrhea (CTCAC v3.0) and the protocol was amended to reduce the Lap dose to 750 mg/day. After modified radical mastectomy (MRM), patients received radiation therapy and one year of adjuvant trastuzumab. Results: Median age was 53.8 (range, 39 -70), performance status was 0 (13 pts), 1 (2 pts), 4 pts had metastatic disease at diagnosis. 10 of 15 pts had MRM. One pt achieved pCR. Five pts did not complete the NAC due to grade 2 cardiomyopathy (1), liver dysfunction (2), diarrhea (1), and insurance denial after pt started treatment (1). The trial was stopped early due to severe toxicity (>15%) and lack of efficacy. Conclusions: Lap in combination with chemotherapy as NAC has a limited anti-tumor activity in pts with HER2+ IBC with a pCR rate of 6.6%. Lap and paclitaxel was associated with severe diarrhea toxicity and required multiple dose reductions of Lap. With the recent promising results in HER2+ NAC studies, the role of Lap should continue to be explored in combination with other anti-HER2 agents in IBC patients.

Outcome of patients with locally advanced breast cancer (LABC) followed at the University of Cincinnati (UC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21160-21160
Author(s):  
R. S. Komrokji ◽  
Z. Nahleh ◽  
S. Dhaliwal ◽  
D. Sivasubramaniam
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Clinical Response ◽  
Locally Advanced Breast Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Pathological Response ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph

21160 Background: LABC poses a difficult clinical challenge . The correlation of complete clinical (cCR) and pathological response rates (pCR) based on molecular tumor characteristics with outcome is of great clinical interest. Methods: We conducted a retrospective chart review on consecutive patients diagnosed with LABC who completed NC between 2001–2006 at UC. Pathological response was classified as pCR (no invasive tumor in breast and axillary lymph nodes), RDLN (disease in lymph nodes), RDB( disease in breast), and RDBLN (disease in both). Overall survival (OS)and event free survival (EFS) were calculated using Kaplan-Meier analysis. Result: We included 45 patients. Median age 51, 40% (n=18) white and 60% (n=27) African American, Stage IIB 9%, IIIA 29%, IIIB 51 % and IIIC 11%. 75 % invasive ductal, 9% invasive lobular and 16% inflammatory breast cancer (IBC). ER+/or PR+ in 47% (18% ER + / PR +, 27% ER +/PR -, 2% ER-/PR+), and 53% ER -/PR-. HER2 neu + ( IHC 3 + or FISH ratio > 2.2) was identified in 27% of patients. NC regimens included: doxorubicin or epirubicine plus taxane (paclitaxel or docetaxel) 80 %, anthracycline only 10%, single agent taxane 4%, and 6% other regimens (2 CMF, 1 capecitabine). One patient received NC with trastuzumab. Response to NC was as follows: Clinically, 55% (n=25) achieved cCR, 38% partial clinical response, 4% stable disease and 2% progressive disease. Pathpogically, pCR was achieved in 22% (n=10) of all patients, 7% pPRLN, 24% pPRB and 47% RDBLN . None of the patients with IBC had pCR. Among ER+ and or PR + tumors , 19% achieved pCR compared to pCR of 25% among ER-/PR-. Among HER2 neu +, 17% achieved pCR compared to 25% in HER2 neu -. Among all patients who achieved cCR, only 36% actually had pCR. For patients who did not achieve pCR, OS and EFS were 5.7 years and 19 months respectively compared to both not yet reached for those with pCR. Conclusion: LABC has poor prognosis overall using standard chemotherapy. Clinical response followingNC was not well predictive of pathological response. ER-/PR - tumors respond better to neoadjuvant chemotherapy compared to ER+/orPR+ tumors. Less than 20% of HER2 neu + tumors achieve pCR before trastuzumab's routine use. More research is urgently needed to optimize treatment strategies and improve outcome of LABC and IBC. No significant financial relationships to disclose.

scholarly journals Breast Cancer with Internal Mammary Node Metastases: A Case Presented in a Tumor Board Session and Decision Making

2019 ◽  
pp. 156-160
Author(s):  
Léamarie Meloche-Dumas ◽  
Erica Patocskai ◽  
Kerianne Boulva ◽  
Moishe Liberman ◽  
Younan Rami
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Tumor Board ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Internal Mammary Chain ◽  
Internal Mammary

Background: There are several therapeutic options available for breast cancer treatment, now incorporating innovative targeted molecular therapies. Metastatic breast cancer is usually treated with chemotherapy and/or hormonotherapy. Surgery has not been shown to improve survival. Adjuvant radiotherapy (RT) has been proven to be effective in the treatment of locally advanced breast cancer, reducing locoregional recurrence. The optimal treatment of internal mammary lymph nodes (IMN) metastases remains controversial. Case presentation: A 48-year-old woman was diagnosed with invasive breast cancer with ipsilateral metastases to axillary lymph nodes and a contralateral IMN metastasis. This case was presented twice during the tumor board sessions of the Surgical Oncology Service at the Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada. Question: Does the internal mammary chain (IMC) dissection could be used as a treatment approach in breast cancer with IMC metastasis? Conclusion: Internal mammary chain dissection should be discussed in tumor board sessions on a case-by-case basis. There are no strong guidelines on the management of IMN metastasis in breast cancer, but there is growing evidence that these women should be treated with curative intent.

scholarly journals Assessment of the Effect of Treatment with Neoadjuvant Chemotherapy on Breast Cancer Axillary Lymph Node

2013 ◽  
Vol 6 (2) ◽  
pp. 82-88
Author(s):  
Savelina L. Popovska ◽  
Ivan N. Ivanov ◽  
Dorian Y. Dikov
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Primary Tumor ◽  
Radiation Treatment ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Scoring Systems ◽  
Cytotoxic Agents ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph

Summary Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer (LABS). The aim of this study was to determine the effects of neoadjuvant chemotherapy on metastatic and nonmetastatic breast cancer axillary lymph nodes (ALNs). Seventy-seven patients with LABS and cytologically documented ALN metastases were treated in two prospective trials. Patients had breast surgery with level I and level II axillary dissection followed by additional chemotherapy or radiation treatment. Clinical nodal status was determined by physical examination and compared with histological and immunohistochemical findings. The regressive changes in primary tumor and ALNs were achieved using scoring systems. Objective clinical response in primary tumor was seen in 48.05% of patients. Histologic evidence of regression was noted in 46 cases (59.75%), with complete histologic regression achieved in 5 cases (6.49%). The number of cases according to the ALNs regression scoring system was as follows: 0 grade - viable metastases without effect - 21 patients (30%); 1 grade - cytotoxic effect in metastases - 20 patients (28.58%), 2 grade - micrometastasis - only3 patients (4.28%); 3 grade - no residual metastatic disease - 1 patient (1.43%); 4 grade - negative ALNs before and after treatment - 25 patients (35.71%). Nodular fibrotic area and iron-loaded macrophages suggested previous presence of tumor metastasis. There was significant relationship between histologic regression in the primary tumor and the presence of effect of cytotoxic agents on ALNs metastases (r=0.9123; p<0.00001). As chemotherapy is widely used in the treatment of breast carcinoma, pathologists should be aware of chemotherapy-induced changes in metastatic and in non­metastatic ALNs.

589 Detection of extra-axillary lymph nodes with FDG PET/CT in patients with locally advanced breast cancer

2010 ◽  
Vol 8 (3) ◽  
pp. 231
Author(s):  
T.S. Aukema ◽  
M.E. Straver ◽  
M.T.F.D. Vrancken Peeters ◽  
N.S. Russell ◽  
K.G. Gilhuijs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Advanced Breast Cancer ◽  
Fdg Pet ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Pet Ct ◽  
Fdg Pet Ct

Epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab and bevacizumab as neoadjuvant therapy for HER2-positive locally advanced breast cancer (LABC) or as adjuvant therapy for HER2-positive pathologic stage III breast cancer (PS3BC): A phase II trial of the NSABP Foundation Research Group

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 580-580
Author(s):  
J. W. Smith ◽  
M. Buyse ◽  
P. Rastogi ◽  
C. Geyer ◽  
S. Jacobs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Locally Advanced Breast Cancer ◽  
Nyha Class ◽  
Locally Advanced ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Class Iii ◽  
Her2 Positive

580 Background: A previous phase II study evaluating the combination of trastuzumab (tras) and bevacizumab (bev) as first-line therapy in HER2 + MBC showed a response rate of 54%. The purpose of this trial is to determine the cardiac safety profile of these agents with docetaxel (T) following epirubicin plus cyclophosphamide (EC) in women with LABC and PS3BC and the activity in those with LABC. Methods: Since June 2007, 75 women with HER-2 + LABC or PS3BC have begun epirubicin 90 mg/m2 IV plus cyclophosphamide 600 mg/m2 IV q3wks x 4 followed by docetaxel 100 mg/m2 IV q3wks x 4. Targeted therapy: Cohort A (neoadjuvant), bev 15 mg/kg IV with Cycle 4 of EC, continued with the first 3 cycles of T. Standard weekly tras with 4 cycles of T. Postop, bev 15 mg/kg IV and tras 6 mg/kg IV q3wks to complete 1 yr of targeted therapy. Cohort B (adjuvant), bev 15 mg/kg q3wks for 4 cycles and weekly tras with T. After chemotherapy, bev and tras q3wks to complete 1 yr of therapy. Primary endpoints were the rate of cardiac events in both cohorts and pCR rate in breast/axillary lymph nodes in Cohort A. Results: Median age was 50 yrs. In Cohort A, 28 (53%) patients (pts) were stage IIIA, 20 (38%) stage IIIB, and 5 (9%) stage IIIC. 13 (25%) had inflammatory BC. A pCR occurred in 19 of the first 36 pts (53%). Toxicity information on the first 73 pts in both cohorts showed that grade 2 LVEF dysfunction has developed in 5 pts and grade 3 LVEF dysfunction in 2, 1 with NYHA Class II and 1 with Class III symptoms. The latter met criteria for a cardiac event. Conclusions: The regimen is active with an acceptable preliminary rate of cardiac toxicity. Updated results will be presented. This trial is conducted with the support of Genentech. [Table: see text]

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