scholarly journals Pathologic Response Rates for Breast Cancer Stages as a Predictor of Outcomes in Patients Receiving Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery

2020 ◽  
Author(s):  
jiaqiang Zhang ◽  
Chang-Yun Lu ◽  
Ho-Min Chen ◽  
Szu-Yuan Wu

Abstract PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients’ PRRs; other independent predictors were controlled for or stratified in the analysis.RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13–0.56), 0.36 (0.15–0.85), and 0.15 (0.08–0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35–0.89), 0.91 (0.62–0.96), and 0.63 (0.43–0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06–2.24), 1.08 (1.03–1.82), and 1.19 (1.07–2.01) for all-cause mortality, LRR, and DM, respectively.CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.

2020 ◽  
Author(s):  
Chang-Yun Lu ◽  
Ho-Min Chen ◽  
Szu-Yuan Wu

Abstract PURPOSE: To determine easy-to-use predictors of overall survival (OS), locoregional recurrence (LRR), and distant metastasis (DM) in patients with breast invasive ductal carcinoma (IDC) receiving neoadjuvant chemotherapy (NACT) followed by breast-conserving surgery (BCS), we obtained pathologic response rates (PRRs) for combined primary and nodal diseases (American Joint Committee on Cancer [AJCC] stages) from clinical and pathologic reports, and we used these as predictors.PATIENTS AND METHODS: We enrolled patients with IDC who had received NACT followed by BCS. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals (CIs) for the patients’ PRRs; other independent predictors were controlled for or stratified in the analysis.RESULTS: We analyzed 1047 patients with IDC (611, 260, and 176 patients in clinical stages IIB, IIIA, and IIIB-C, respectively) receiving NACT and BCS. After multivariate Cox regression analyses, the adjusted HRs (aHRs; 95% CI) in patients with pathologic complete response (ypT0N0) were 0.26 (0.13–0.56), 0.36 (0.15–0.85), and 0.15 (0.08–0.31) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with downstaging of AJCC stages were 0.55 (0.35–0.89), 0.91 (0.62–0.96), and 0.63 (0.43–0.91) for all-cause mortality, LRR, and DM, respectively. The aHRs (95% CI) in patients with upstaging of AJCC stages were 1.77 (1.06–2.24), 1.08 (1.03–1.82), and 1.19 (1.07–2.01) for all-cause mortality, LRR, and DM, respectively.CONCLUSION: The impacts of AJCC-stage PRRs are useful predictive tools and strong predictors for OS, LRR, and DM in patients with breast IDC receiving NACT followed by BCS.


2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 267-267 ◽  
Author(s):  
Jonathan Lawrence Wright ◽  
Franklin Lee ◽  
William Proctor Harris ◽  
Heather H. Cheng ◽  
Song Zhao ◽  
...  

267 Background: Neoadjuvant chemotherapy for muscle invasive urothelial carcinoma (UC) of the bladder is associated with higher rates of pathologic complete response (CR) and improved disease-specific survival compared to those treated with radical cystectomy (RC) alone. Two standard regimens used are (1) gemcitabine and cisplatin (GC); and (2) methotrexate, vinblastine, adriamycin, and cisplatin (MVAC), with debate on whether there is a difference in clinical efficacy. In this analysis, we compare the pathologic outcomes at cystectomy between neoadjuvant GC and MVAC treatment. Methods: Data was retrospectively collected on patients with T2-T4 UC of the bladder who underwent RC between Sept 2003 and December 2011 at the University of Washington. Clinical and pathologic factors were recorded along with neoadjuvant chemotherapy and comorbidities. Pathologic outcomes included those with CR (pT0) and near CR (nCR = pT0/Ta/Tis). Odds ratio (OR) for CR and nCR were calculated using multivariate logistic regression adjusting for demographic (age, gender, race), medical (creatinine, diabetes mellitus, cardiac disease) and clinical factors (clinical T stage, prior BCG therapy, complete tumor debulking prior to chemotherapy). Results: A total of 78 patients received GC or MVAC neoadjuvant chemotherapy followed by RC, including 46 who received GC and 32 who received MVAC. There was no difference in gender, renal function, cardiac disease or clinical stage between the two groups. Patients over 70 years of age primarily received GC (17/18). CR was achieved in 30% and 25% (p = 0.15) of GC and MVAC patients, respectively (multivariate OR 0.42, 95% CI 0.11-1.63). nCR was more common in those receiving GC (50% vs. 38%, p = 0.04) although non-significant in the multivariate model (OR 0.30, 95% CI 0.07-1.16). Conclusions: We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of bladder cancer patients. These observations support the use of GC as an alternative regimen in the neoadjuvant setting.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
W. Symmans ◽  
F. Peintinger ◽  
C. Hatzis ◽  
H. Kuerer ◽  
V. Valero ◽  
...  

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]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12625-e12625
Author(s):  
Elena Parvez ◽  
Thierry Muanza

e12625 Background: Pathologic complete response(pCR) after neoadjuvant chemotherapy(NAC) in patients with breast cancer(BC) is associated with decreased recurrence and improved survival. In NSABP B18 and B27, 10-yr locoregional recurrence(LRR) after pCR in patients with Stage I-III BC undergoing breast conserving surgery(BCS) and whole breast RT(WBRT) was 5.2-6.9%. However, LRR may be overestimated as Her2 therapy was not used and only some eligible patients received endocrine therapy. A retrospective study using modern protocols found a 5-yr LRR of up to 2.6%. We hypothesize that LRR in N0 patients is even lower, and de-escalation of therapy should be examined. The study objective is to assess if a prospective trial of omission of WBRT after BCS in patients with N0 BC and pCR after NAC is warranted and to assess feasibility. Methods: Patients with T1-T3 N0 invasive BC diagnosed between Dec 2011-2017 treated with NAC and BCS were identified from a hospital BC registry. Health records were retrospectively reviewed to identify patients with pCR, defined as absence of residual invasive or in-situ disease(ypT0N0). Incidents of locoregional and distant recurrence were recorded. Results: Of 89 patients with T1-3 N0 invasive BC treated with NAC and BCS, 29(32.6%) had pCR. Median follow-up was 61.1 months. Median age was 55 yrs and median tumour size was 2.4cm. Receptor status was 16(55.2%) HR-Her2-, 4(13.8%) HR-Her2+, 7(24.1%) HR+Her2+ and 2(6.9%) HR+Her2-. NAC protocols consisted of an anthracycline and/or a taxane in 27(90%) patients, and 6 patients were treated on NAC trials. All patients with Her2+ disease received Her2 targeted therapy. Adjuvant endocrine therapy was taken by 8 of 9 patients with HR+ disease. All patients received WBRT without nodal RT. RT plan was available for 26(86.7%) patients. RT dose ranged from 40-50Gy, and all but 4 received tumour bed boost. There were no local or regional recurrence events at last follow-up. One patient developed brain metastases at 15.7 months. Conclusions: Over 6 years, 29 patients were identified that would be eligible for a prospective trial evaluating omission of WBRT after pCR in N0 patients treated with NAC and BCS. At median 5-yr follow-up, there were no locoregional recurrences in our cohort, demonstrating that the absolute benefit provided by WBRT is likely small. Our results indicate a prospective trial is warranted and will require multi-institution participation to accrue.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5043-5043
Author(s):  
Praful Ravi ◽  
Gregory Russell Pond ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Rohit K. Jain ◽  
William Paul Skelton ◽  
...  

5043 Background: Pathologic complete response (pCR) after NAC for MIBC is strongly correlated with long-term overall survival. However, there are sparse data on the risk of recurrence based on depth of pathologic response (pT0, pTa, pTis, pT1), and the differential impact of clinicopathologic factors and NAC regimen on recurrence. Methods: Baseline data on all pts with cT2-4N0-1 MIBC receiving NAC and who achieved < ypT2N0 disease at radical cystectomy (RC) from 9 international centers were obtained. The key outcome was time to recurrence (TTR) – defined as the time to any recurrence in the urinary tract or regional/distant metastasis, with death (in the absence of recurrence) considered a competing risk. Cox regression analysis was used to analyze the impact of clinical factors on recurrence. Results: A total of 506 pts were available. Median age was 66 years (range 33-86) and 78% (n = 396) were male; median follow-up after RC was 2.6 years. The majority of patients had pure urothelial histology (n = 371, 73%), and baseline stage was cT2N0 (n = 368, 73%), cT3-4N0 (n = 95, 19%) and TanyN1 (n = 43, 9%). NAC regimens were gemcitabine-cisplatin (GC, n = 296, 59%), dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC, n = 141, 28%), split-dose GC (n = 29, 6%), MVAC (n = 29, 6%) and non-cisplatin based regimens (n = 11, 2%). At RC, 304 patients (60%) had ypT0N0 disease, 32 (6%) had ypTaN0, 107 (21%) had ypTisN0 and 63 (13%) had ypT1N0. Overall, 43 patients (8%) recurred with a median TTR of 56 weeks (range 7-251); 5-year freedom from recurrence was 87% (95% CI 83-91). The majority (n = 38) recurred outside the urinary tract. On multivariable analysis, ypTa (HR = 3.36 [1.24-9.11]) and ypT1 (HR = 2.88 [1.33-6.22], p = 0.013) disease at RC were predictors of shorter TTR, while female sex was associated with longer TTR (HR = 0.52 [0.27-0.98], p = 0.043). The type of NAC was not predictive of TTR (GC vs. other, HR = 1.49 [0.75-2.97], p = 0.26). Conclusions: To our knowledge, this is the largest study to quantify the risk of recurrence in pts achieving pathologic response after NAC and RC for MIBC. 8% of patients undergoing NAC and achieving < ypT2N0 at RC recurred. Residual ypTa and ypT1 disease conferred a significantly higher risk of recurrence, while ypTis did not; female sex was associated with a lower risk of recurrence. Importantly, the type of cisplatin-based NAC regimen used was not an independent predictor of recurrence.


2007 ◽  
Vol 25 (15) ◽  
pp. 2012-2018 ◽  
Author(s):  
Günther G. Steger ◽  
Arik Galid ◽  
Michael Gnant ◽  
Brigitte Mlineritsch ◽  
Alois Lang ◽  
...  

Purpose Preoperative (neoadjuvant) chemotherapy for operable breast cancer downstages tumors initially not suitable for breast-conserving surgery. A pathologic complete response (pCR) to neoadjuvant chemotherapy may be a surrogate for longer overall survival, but this beneficial effect remains to be established. This phase III trial evaluated whether doubling the number of cycles of neoadjuvant treatment increased the pCR rate. Patients and Methods Patients with biopsy-proven breast cancer (T1-4a-c, N±, M0; stage I to III) were eligible and randomly assigned to either three or six cycles of epirubicin 75 mg/m2 and docetaxel 75 mg/m2 on day 1 and granulocyte colony-stimulating factor on days 3 through 10 (ED+G), every 21 days. The primary end point was the pCR rate of the breast tumor. Secondary end points were pathologic nodal status after surgery and the rate of breast-conserving surgery. Results A total of 292 patients were accrued, and 288 patients were assessable for efficacy and safety. Groups were well balanced for known prognostic factors. Six cycles of ED+G, compared with three cycles, resulted in a significantly higher pCR rate (18.6% v 7.7%, respectively; P = .0045), a higher percentage of patients with negative axillary status (56.6% v 42.8%, respectively; P = .02), and a trend towards more breast-conserving surgery (75.9% v 66.9%, respectively; P = .10). Rates of adverse events were similar, and no patients died on treatment. Conclusion Doubling the number of neoadjuvant ED+G cycles from three to six results in higher rates of pCR and negative axillary nodal status with no excess of adverse effects. Thus, six cycles of ED+G should be the standard neoadjuvant treatment for operable breast cancer if this combination is chosen.


2014 ◽  
Vol 260 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Judy C. Boughey ◽  
Linda M. McCall ◽  
Karla V. Ballman ◽  
Elizabeth A. Mittendorf ◽  
Gretchen M. Ahrendt ◽  
...  

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