scholarly journals Neoadjuvant Therapy with Doxorubicin-Cyclophosphamide Followed by Weekly Paclitaxel in Early Breast Cancer: A Retrospective Analysis of 200 Consecutive Patients Treated in A Single Center with A Median Follow-Up of 9.5 Years.

Author(s):  
Lisi M. Dredze ◽  
Michael Friger ◽  
Samuel Ariad ◽  
Michael Koretz ◽  
Bertha Delgato ◽  
...  

Abstract Purpose We analyzed outcomes of doxorubicin-cyclophosphamide(AC) followed by weekly paclitaxel as neoadjuvant chemotherapy(NAC) for breast cancer(BC), in an everyday practice with long-term follow-up of patients. Methods All patients (n=200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007(n=99); and subsequently every 2 weeks (dose dense)(dd)(n=101). Clinical pathologic features, treatment course and outcome information were recorded. Complete pathologic response(pCR) was analyzed according to BC subtype, dose regimen and stage. Results Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human-epidermal-growth-factor receptor(HER 2)-positive 32.5% (of whom 82% received trastuzumab), hormone-receptor positive/HER2 negative 53%, triple negative 14.5%. Breast conserving surgery(BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival(EFS), and overall survival(OS) is 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS. Conclusions- NAC for BC with AC-paclitaxel can be safely administered in the “real-world’ setting with high efficacy. Current efforts are aimed at Increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3045-3045
Author(s):  
J. Horiguchi ◽  
Y. Koibuchi ◽  
N. Rokutanda ◽  
R. Nagaoka ◽  
M. Kikuchi ◽  
...  

3045 Background: The purpose of this study is to determine the clinical efficacy of neoadjuvant paclitaxel and trastuzumab in women with advanced breast cancer, with or without metastatic disease. Methods: Patients with HER2-positive breast cancer (clinical stage IIB-IV) were included in this study. The patients received trastuzumab 4mg/kg loading dose intravenously then 2mg/kg weekly and concurrently paclitaxel 80mg/m2 (Day 1, 8, 15) weekly for 4 cycles followed by surgery. Results: Preliminary results from 15 patients are reported. Of these, six patients (40%) had a clinical complete response and nine patients (60%) a clinical partial response. Fourteen of 15 patients received surgery; eight breast-conserving surgery and six modified radical mastectomy. Six patients (43%) had pathological complete response. With a median follow-up of 19 months (range, 5–32 months), these 15 patients are alive. Patients with clinical stage IIB-III breast cancer are alive without any distant metastasis. Conclusion: Combined neoadjuvant weekly paclitaxel and trastuzumab had high clinical and pathological response rates for HER2 overexpressing breast cancer. No significant financial relationships to disclose.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Angeliki Andrikopoulou ◽  
Kleoniki Apostolidou ◽  
Spyridoula Chatzinikolaou ◽  
Garyfalia Bletsa ◽  
Eleni Zografos ◽  
...  

Abstract Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.


2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 284-284
Author(s):  
U. Zurawska ◽  
D. A. Baribeau ◽  
C. Victor ◽  
S. Giilck ◽  
A. Florescu ◽  
...  

284 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.


2021 ◽  
Author(s):  
Angeliki Andrikopoulou ◽  
Kleoniki Apostolidou ◽  
Spyridoula Chatzinikolaou ◽  
Garyfalia Bletsa ◽  
Eleni Zografos ◽  
...  

Abstract Background Over than one third (28–58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. Methods Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words “breast”, “cancer”, “trastuzumab” and “pregnancy”. This study was performed in accordance with the PRISMA guidelines. Results A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1–32). Oligohydramnios or anhydramnios was the most common (58.1 %) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher’s exact test). In 43.3% of cases a completely healthy neonate was born. 41.7 % of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. Conclusions Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11561-e11561
Author(s):  
Miguel J. Sotelo ◽  
Luis Manso ◽  
José Ángel Garcia Saenz ◽  
Eva M. Ciruelos ◽  
Fernando Moreno ◽  
...  

e11561 Background: Trastuzumab and lapatinib show complementary and non-cross resistant mechanisms of anti-HER2 action. Dual HER2 blockade has been preclinically and clinically assessed with encouraging results. Trastuzumab and lapatinib combination is effective in terms of survival in patients with heavily pretreated HER2-positive mBC. We aim to report our experience with lapatinib plus trastuzumab in this setting. Methods: Descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing metastatic breast cancer treated in two institutions from 01/2007 to 12/2012. The objective of this analysis is to report the response rate (RR), progression-free survival (PFS) and toxicity. Results: 23 HER2-positive mBC patients previously treated with trastuzumab received trastuzumab plus lapatinib based therapy. 15 patients (65%) received 2 or more previous lines. 17 patients (74%) had visceral disease. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%) whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. Chemotherapeutic drugs most used were: capecitabine (54%) and vinorelbine (15%). RR: partial response 22% (5/23), stable disease 39% (9/23). Median of follow-up was 11 months. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, while PFS in patients with HT was only 2. PFS in hormone receptor positive and negative was 3 and 5 months respectively. The most common toxicities were: diarrhea (48%), anemia (39%), asthenia (39%) and hand-and-foot syndrome (17%). Grade ≥ 3 toxicity was diarrhea (26%) and hand-and-foot syndrome (9%). The incidence of cardiotoxicity was 9% (grade 2). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible and active in heavily pretreated HER2-positive mBC patients. However, further investigation is warranted to demonstrate superiority over sequential blockade with trastuzumab and lapatinib in this setting.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12045-e12045
Author(s):  
Michael Lee ◽  
Sheridan Wilson ◽  
David James Porter

e12045 Background: 3rd generation adjuvant chemotherapy regimens for breast cancer include FEC every three weeks (Q3W) x 3 cycles and Docetaxel (D) Q3W or weekly paclitaxel (P1W) x 9 weeks (FEC-D/P1W) and AC Q3W x 4 followed by P1W x 12 weeks or D x 4 cycles (AC-P1W). These regimens were developed independently and have not been directly compared. Real world effect of weekly paclitaxel schedule is unknown. Methods: Women with stage 1-3 breast cancer who received 3rd generation adjuvant chemotherapy (with 1 year of adjuvant trastuzumab if HER2+) between 2010-2015 inclusive were identified in the New Zealand Breast Cancer Database. Taxane regimens Q3W D and P1W were grouped for analysis. We compared 5 year overall survival (OS) between shorter FEC-D/P1W (total 6 cycles) and longer AC-P1W or Docetaxel Q3W x 4 cycles (total 8 cycles). Patients who received other taxane schedules or non-standard duration of chemotherapy were excluded. Results: 772 women received the FEC-D/P1W regimen and 488 were treated with AC-P1W. The FEC-D/P1W had more grade II/III disease (96.4% v 93.8%), BMI ≥30 (44.7% v 34.5%), HER2 positive (37.8% v 23.6%) and higher chemotherapy completion rate (95.1% v 83.8%). The AC-P1W cohort had higher nodal positive cases (97.1% v 80.6%). Univariate analysis showed no statistical significance for age, BMI, ethnicity, histological subtype and surgery type but tumour grade, stage and hormone status were significant. We constructed a cohort (n = 926) matched for these factors. After median follow up 27 months, 5yr OS for case matched cohort is 87.4% for FEC-D/P1W v 86.4% for AC-D/P1W (p = 0.825) with HR 0.96 (95%CI 0.67-1.38) in favour of FEC-D/P1W. Conclusions: These results suggest one can de-escalate chemotherapy by using a 6 cycle anthracycline/taxane regimen offering an opportunity to reduce the burden of chemotherapy without compromising survival.


2019 ◽  
Vol 106 (4) ◽  
pp. 301-305
Author(s):  
Eufemia S. Lutrino ◽  
Laura Orlando ◽  
Antonio Febbraro ◽  
Marianna Giampaglia ◽  
Claudio Zamagni ◽  
...  

Background: Chemotherapy plus targeted therapy is the established treatment for human epidermal growth factor receptor 2 (HER2)–overexpressing breast cancer (BC). Limited data regarding the safety and activity of the combination of eribulin and trastuzumab (E/T) in pretreated HER2-positive advanced BC (ABC) are available. The aim of this observational, retrospective, multicenter study was to examine the tolerability and the clinical activity of E/T in this setting. Methods: Patients treated with eribulin mesylate plus standard dose of trastuzumab were included. Data on overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were reported. Results: Between October 2012 and November 2015, 24 consecutive patients with HER2-positive ABC were included. All patients were heavily pretreated: the median number of prior chemotherapy regimens for ABC was 3 (range 2–9). The median number of cycles with E/T was 11.5 (range 2–26). The ORR was 41.7%. Median PFS was 5.4 months, median postprogression survival was 5.4 months, and median OS was 8 months. Neutropenia was the most common grade 3/4 clinical adverse event (16.7%). Conclusions: Tolerability and clinical activity of the E/T combination schedule are encouraging. The results of this study indicate that this combination might be considered for treatment of pretreated HER2 ABC.


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