scholarly journals Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype

2017 ◽  
Vol 35 (10) ◽  
pp. 1049-1060 ◽  
Author(s):  
W. Fraser Symmans ◽  
Caimiao Wei ◽  
Rebekah Gould ◽  
Xian Yu ◽  
Ya Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Validation Cohort ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Her2 Positive ◽  
Free Survival ◽  
Residual Cancer Burden

Purpose To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)–targeted treatment. Methods We conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor–negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC [n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinical-pathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor–negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Conclusion RCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.

Results of a novel neoadjuvant chemotherapy (NAC) regimen for breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11610-e11610
Author(s):  
Noridza Rivera-Rodriguez ◽  
Fernando Cabanillas ◽  
Lesley Lawrenson ◽  
Viviana Negron ◽  
Orestes Antonio Pavia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Free Survival ◽  
Residual Cancer Burden ◽  
Significant Difference

e11610 Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N=19) or triple negative breast cancer (TNBC) (N=15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB= 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB=3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p=0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p=0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below. Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Clinical trial information: NCT 00830544. [Table: see text]

scholarly journals Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

2012 ◽  
Vol 30 (26) ◽  
pp. 3242-3249 ◽  
Author(s):  
Laura J. Esserman ◽  
Donald A. Berry ◽  
Angela DeMichele ◽  
Lisa Carey ◽  
Sarah E. Davis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Biology ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
High Risk Group ◽  
Hazard Ratio ◽  
Recurrence Free Survival ◽  
Her2 Positive ◽  
Free Survival

PurposeNeoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.Patients and MethodsEligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.ResultsIn 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.ConclusionIn this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

scholarly journals Effect of Trastuzumab among HER2-Positive Breast Cancer Patients that Achieved Pathologic Complete Response after Neoadjuvant Chemotherapy

Breast Care ◽  
2019 ◽  
Vol 14 (6) ◽  
pp. 388-393
Author(s):  
Xinguang Wang ◽  
Yingjian He ◽  
Zhaoqing Fan ◽  
Tianfeng Wang ◽  
Yuntao Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Free Survival ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Background: We sought to investigate the incremental benefit of trastuzumab in patients with HER2-positive breast cancer who achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT). Methods: The data of HER2-positive invasive breast cancer patients treated with NACT and achieving pCR were obtained from the institutional database. Patients were categorized according to trastuzumab administration. The Kaplan-Meier method and log-rank estimates were used to test the association between trastuzumab administration and survival. Univariate and multivariate Cox regressions were used to obtain hazard ratios. Results: Of 223 patients, 83 (37.2%) were treated with NACT without trastuzumab and 140 (62.8%) were treated with NACT plus trastuzumab for 1 year. After a median follow-up of 67 months, the trastuzumab group showed improved relapse-free survival compared with the no-trastuzumab group (95.7 vs. 87.8%, hazard ratio = 0.31, p = 0.028). No significant difference in distant disease-free survival or overall survival was observed (p = 0.250 and 0.432, respectively). Multivariate analysis identified endocrine therapy and trastuzumab administration to be associated with decreased risk of relapse (p = 0.018 and 0.030, respectively). Conclusion: The administration of trastuzumab should be considered standard treatment for HER2-positive patients who have achieved pCR after NACT alone.

scholarly journals Image-guided vacuum-assisted biopsy to assess pathologic complete response in breast cancer patients with exceptional response to neoadjuvant chemotherapy.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 39-39
Author(s):  
Victoria Teoh ◽  
Fiona MacNeill ◽  
Nicola Roche ◽  
Gerald Gui ◽  
Romney Pope ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Invasive Ductal Carcinoma ◽  
Ductal Carcinoma ◽  
Residual Disease ◽  
False Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Her2 Positive ◽  
Image Guided

39 Background: Image-guided vacuum-assisted biopsy (VAB) is increasingly used after completion of neoadjuvant chemotherapy (NAC) to assess residual disease in the breast, facilitate risk-adaptive surgery and potentially identify exceptional responders who may not require surgical intervention. The aim of this analysis was to investigate the diagnostic performance of a standardized post-NAC VAB protocol, developed following retrospective analysis of institutional data (1). Methods: Prospective cohort study of patients with HER2 positive and triple negative (TN) invasive ductal carcinoma, treated with NAC, who had partial/complete imaging response and underwent post-NAC VAB to aid surgical planning between 02/2018 and 06/2019. The aim of VAB was to sample the site of residual imaging abnormality (breast residuum <2cm) previously marked by clip insertion. Pathologic complete response (pCR) was defined as no residual disease in the breast (ypT0). Diagnostic accuracy of VAB was calculated using final surgical pathology as the reference standard. Simple descriptive statistics were performed. Results: 26 eligible patients underwent post-NAC VAB. This was representative in 23 cases. The overall pCR rate was 46.2% (42.1% for HER2 positive, 57.1% for TN phenotypes). The post-NAC VAB false negative rate (FNR) was 9.1% (95% CI: 0-26.1) and the negative predictive value (NPV) was 90.91% (95% CI: 60.27-98.51) with an overall accuracy of 86.96% (95% CI: 66.41-97.22). Conclusions: This data suggests that post-NAC VAB may reliably predict pCR in patients with HER2 positive and TN invasive ductal carcinoma with good response to NAC. Further technical refinements in VAB technique, standardization in patient selection and prospective trials are warranted to further explore the role of post-NAC VAB in supporting minimal or no surgery trials. References 1. Tasoulis MK, Roche N, Rusby JE, Pope R, Allen S, Downey K, Nerurkar A, Osin P, Wilson R, MacNeill F. Post neoadjuvant chemotherapy vacuum assisted biopsy in breast cancer: Can it determine pathologic complete response before surgery? J Clin Oncol 2018;36 (Supplement): abstr 567.

Safety and effectiveness of dose dense neoadjuvant chemotherapy in patients with stage II/III breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10622-10622
Author(s):  
S. A. McDaniel ◽  
H. Krontiras ◽  
J. T. Carpenter ◽  
L. M. Nabell ◽  
K. I. Bland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
Dose Dense ◽  
To Receive

10622 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy either pre- or postoperatively; OS and DSF rates at 9 years were identical. Importantly, pathologic complete response (pCR) was directly proportional to DFS and OS. Recently, dose dense adjuvant chemotherapy has shown a statistically significant improvement in DFS and OS. However, no data is available for the use of dose dense preoperative chemotherapy at this time. Methods: Women enrolled in the I-SPY correlative trial with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were evaluated to assess response rates and safety to dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2 wks × 4, paclitaxel 175 mg/m2 IV Q2 wks × 4, and cyclophosphamide 600 mg/m2 IV Q2 wks × 4). Results: Since 02/2003, 43 pts have been treated with dose dense neoadjuvant chemotherapy on the I-SPY trial at UAB (mean age 47.9). 47% of the pts were ER+, 37% were PR+ and 5% were Her2+ by FISH. 2 pts dropped out for personal reasons and 9 pts are actively undergoing treatment. Overall, 32 pts received dose dense chemotherapy and proceeded to surgery. Of those, 31 received dose dense sequential ATC and 1 received dose dense concurrent AC followed by T. 34% had a pCR (breast & nodes) while an additional 10% had a pCR in the breast but residual disease in lymph nodes; 41% had a PR; 9% had SD; and 6% had PD. Hematologic toxicity consisted of grade 3 anemia in 2 pts, febrile neutropenia in 2 pts and no grade 4 thrombocytopenia. Non-hematologic grade 3–4 toxicity consisted of mediport-associated thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and disseminated varicella in 1 pt. Conclusion: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast & nodes) in about 1/3 of patients (34%) with tolerable toxicity. No significant financial relationships to disclose.

A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
W. Symmans ◽  
F. Peintinger ◽  
C. Hatzis ◽  
H. Kuerer ◽  
V. Valero ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Continuous Measure ◽  
Residual Cancer ◽  
Cancer Burden ◽  
Residual Cancer Burden ◽  
Ajcc Stage

536 Background: The strength of association between tumor response and survival is critical for neoadjuvant chemotherapy trials. Pathologic complete response (pCR) reliably predicts survival benefit, but residual disease contains a range of pathologic responses that likely contain different prognostic groups, including near complete response and resistance. Methods: Pathologic slides and reports were reviewed from 432 patients in two completed neoadjuvant trials: 1) fluorouracil, doxorubicin and cyclophosphamide (FAC) in 189 patients, and 2) paclitaxel followed by FAC (T/FAC) in 243 patients. Paclitaxel was administered as twelve weekly (n=126) or four 3-weekly cycles (n=117). Residual cancer burden (RCB) was calculated as an index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We compared four RCB categories, from RCB-0 (pCR) to RCB-3 (chemoresistant), and post-treatment revised AJCC Stage (0-III) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses (stratified by ER status). Results: The pCR rate was greater after T/FAC than FAC (24% vs. 16%, LR p<0.05), and after weekly (vs. 3-weekly) paclitaxel in T/FAC (30% vs. 16%, LR p<0.01). In patients with residual disease, RCB measurements were significantly lower after T/FAC than FAC (t-test, p<0.0001), but were not different between paclitaxel schedules in T/FAC. RCB was a continuous predictor of DRFS after T/FAC (HR=1.86, 95%CI 1.51–2.30) or FAC (HR=1.67, CI 1.38–2.01) with median follow-up 5 and 8 years, respectively. The resistant category RCB-3 predicted relapse more strongly than AJCC Stage III and identified a larger group of high-risk patients ( Table ). Conclusions: RCB is a new continuous measure of pathologic response that is defined from routine pathologic materials, represents the distribution of residual disease, is a significant predictor of DRFS, and defines chemotherapy resistance more effectively than revised AJCC Stage. [Table: see text] [Table: see text]

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