Long-term outcomes of patients with HER2+ breast cancer with small-size residual disease (≤ypT1) in the absence of pathological response after trastuzumab-based neoadjuvant chemotherapy and without adjuvant T-DM1: A monocentric retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 589-589
Author(s):  
Ludovic Doucet ◽  
Camille Moreau-Bachelard ◽  
Carole Gourmelon ◽  
Marie Robert ◽  
Dominique Berton ◽  
...  

589 Background: The Katherine trial has shown that adjuvant T-DM1 improved invasive disease free survival (iDFS) of patients with HER2+ breast cancer who did not achieve a pathological complete response (pCR) with trastuzumab-based neoadjuvant chemotherapy (NAC). However, some subgroups may benefit less from this treatment escalation. Methods: All HER2+ breast cancer patients treated with trastuzumab-based NAC between 2006 and 2016 were retrieved from our institution’s database. Neo- or adjuvant T-DM1 was an exclusion criterion. We then selected the patients who did not achieve a pCR and analyzed the outcome (iDFS and overall survival (OS)) according to ypT, ypN and several factors analyzed in the Katherine trial. Results: Out of the 182 patients, 117 patients reached the inclusion criteria. Patient’s characteristics were similar to the trastuzumab arm of the Katherine trial. With a median follow-up of 75.4 months (29.3–149.7), 28 events (24%) occurred, among which 22 distant relapses. In univariate analysis, ≤ypT1 vs > ypT1, ypN0 vs ypN+, no capsular rupture, signs of histological response (Sataloff not D in T or N) were associated with a better iDFS. In multivariate analysis, only ypT status remained significant. Of note, patients with ≤ypT1 (ypTis, ypT0, ypTmic, ypT1) (n = 81; 69%) had an excellent outcome: 3 years (y) and 5y iDFS rates of 90% (83.6-96.8) and 88.6% (81.9-95.9) respectively. The remaining patients (n = 36; 31%) had a significantly lower 3y and 5y iDFS: 69.2% (55.6-86.2) and 59.5% (45-78.6) respectively (p = 0.0017). OS in a multivariate analysis was also improved in pts with the smaller residual and/or node negative disease (3y OS rates of 100% (100-100) vs 92.1% (85.7-99); 5y OS rates of 96% (90.7-100) vs 81.1% (71.6-91.9); p = 0.02). Conclusions: In the absence of pCR after trastuzumab-based NAC, patients with pathological response scored as ≤ypT1 (ypTis,ypT0, ypTmic, ypT1) have an excellent outcome. These patients may derive less benefit from adjuvant T-DM1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11533-e11533
Author(s):  
Cynthia Mayte Villarreal-Garza ◽  
Enrique Soto-Perez-de-Celis ◽  
Erika Sifuentes ◽  
Yanin Chavarri Guerra ◽  
Santiago Ruano ◽  
...  

e11533 Background: The most accurate definition of pathologic complete response (pCR) in HER2+ BC patients (pts) receiving T-based neoadjuvant chemotherapy associated with improved DFS is controversial, particularly regarding the role of residual ductal carcinoma in situ (ypTis) and focal invasive residuals (ypT1mic). The effect of pCR on DFS in various subgroups of HER2+ BC is also uncertain. Methods: Pts with localized HER2+ BC that received T-based neoadjuvant chemotherapy at NCI between January 2007 and May 2012 were identified. We conducted an exploratory analysis of DFS in pts according to their tumor response. DFS curves were derived from Kaplan-Meier estimates and compared by log-rank test. Multivariate analysis was performed using Cox’s regression model. Results: 243 pts were included for analysis. Median follow-up was 39 months (mo). 49% of pts had no invasive and no in situ residuals at surgery (ypT0), 14.4% had ypTis/ypT1mic residuals and 36.6% had gross residual BC. DFS was significantly superior in pts with both ypT0 and ypTis/ypT1mic (no gross invasive residual BC) compared with those with gross residual disease (60.6 and 62.7 mo respectively vs. 51.6 mo, p=0.011 and 0.017). There was no difference in DFS between ypT0 and ypTis/ypT1mic pts (p=0.402). The rate of no gross invasive residual BC was significantly superior in pts with ER-PR- tumors compared with patients with ER+/PR+ tumors (69.9% vs. 56.7%, p=0.034). No gross invasive residual BC was associated with improved DFS in pts with HER2+ ER-/PR- (60.3 vs. 49.0 mo; p=0.005), as opposed to HER2+ ER+/PR+ tumors (61.0 vs. 51.6 mo; p=0.100). Multivariate analysis showed that tumor size (p=0.013) and no gross invasive residual BC (p=0.13) were associated with improved DFS in all subgroups. Conclusions: The absence of gross invasive residual BC was associated with improved DFS in pts with HER2+ BC treated with T-based neoadjuvant chemotherapy, particularly in those with HER2+ ER-/PR- BC. Our data suggest a comparable DFS in HER2+ BC patients with no gross invasive residual BC regardless of the presence or absence of both ypTis and ypT1mic disease after neoadjuvant treatment.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11118-11118
Author(s):  
Julieta Leone ◽  
Jose Pablo Leone ◽  
Carlos Teodoro Vallejo ◽  
Juan Eduardo Perez ◽  
Alberto Omar Romero ◽  
...  

11118 Background: Neoadjuvant chemotherapy is a standard treatment in stage III breast cancer. Prognostic factors can help to identify patients (pts) with high risk of recurrence. The aim of this study was to assess several prognostic factors after a long follow-up, in stage III breast cancer pts, treated with neoadjuvant chemotherapy. Methods: We evaluated 126 pts with stage III breast cancer that participated in a phase-II randomized trial of neoadjuvant 5-fluorouracil, doxorubicin and cyclophosphamide (FAC every 21 days) compared with cyclophosphamide, methotrexate and 5-fluorouracil (CMF days 1 and 8 every 28). Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Response was assessed by WHO criteria. Results: The median age was 52 years (range 24-75). Median follow-up was 4.5 years (range 0.2-16.4), disease free survival (DFS) 4.8 years and overall survival (OS) 6.4 years. Results of the phase-II study showed no difference in efficacy between groups. Univariate analysis showed that the number of pathologically involved lymph nodes (pLN), pathologic response and estrogen and progesterone receptor status correlated with DFS and OS. Number of pLN was the only prognostic factor with statistical significance in Cox regression test for both, DFS and OS (P=0.0004 and P=0.0006, respectively). In a subgroup analysis of pts with pLN, we found no difference in survival when we compared FAC with CMF. Conclusions: The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival. The subset of pts with pLN had similar survival regardless of the regimen used. Clinical trial information: NCT00002696.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12033-e12033
Author(s):  
Tahir Mehmood ◽  
Muhammad Ali ◽  
Kamran Saeed ◽  
Atif Munawar ◽  
Sadaf Usman ◽  
...  

e12033 Background: Pakistan has the highest rate of breast cancer for any South Asian population and majority of the patients present with locally advanced or metastatic disease. We report on response and survival of primary locally advanced non-metastatic breast cancer in women treated with neoadjuvant Adriamycin/Taxanes (AT) based regimens at our institute. Methods: Between 1995 to 2009 the hospital information system identified 517 women with pathologically confirmed locally advanced breast cancer. All patients received neoadjuvant chemotherapy with AT based regimen followed by surgery. Median age was 43 years (range 17-71 years). AJCC stage; stage II 54% and stage III 46% of the patients. Axillary nodes were palpable in 72% of the patients at presentation. Histological sub-types; infiltrating ductal carcinoma 95%, infiltrating lobular carcinoma 3% and others 2% respectively. Pathological grade was I/II in 44% and grade III 56% of the patients. ER, PR, and Her2-neu receptors were positive in 44%, 40% and 24% of the patients respectively. Twenty one percent of the patients had triple negative breast cancer. Post operative radiotherapy was delivered to 94% of the patients. Patients with positive ER/PR receptors also received hormonal manipulation. Results: Following neo-adjuvant chemotherapy, pathological response was; complete response (CR) 13.5%, partial response 21%, stable disease 52% and progressive disease in 13% of the patients respectively. Breast conservation was possible in 36% of the patients. The 5 year disease free survival in patients with and without CR was 81% and 36% respectively. On multivariate analysis, T stage (p = 0.001) and response to neo-adjuvant chemotherapy (p = 0.001) were found to be independent predictors for disease free survival. Conclusions: Pathological response to neoadjuvant chemotherapy is a predictor of long term survival. Chemotherapy regimens with high response rates merit evaluation in randomized trials to improve outcome in locally advanced breast cancer.


2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 65-65
Author(s):  
T. Jonathan Yang ◽  
Monica Morrow ◽  
Shanu Modi ◽  
Kate Krause ◽  
Chun Siu ◽  
...  

65 Background: The relative contribution of biological subtype and response to neoadjuvant chemotherapy (NAC) to locoregional recurrence (LRR) is uncertain. We aim to determine if these factors identify a high risk population for LRR. Methods: 233 patients received anthracycline/taxane-based NAC, mastectomy and postmastectomy radiation therapy (PMRT) in 2000-2009 for Stage II-III breast cancer. 53% (n=123) were HR+ (ER or PR+/HER2-), 23% (53) HER2+ (HER2+/HR+ or HR-), and 24% (57) TN (HR-/HER2-). 76% of HER2+ received trastuzumab. Median PMRT dose was 50 Gy to chest wall and regional nodes. Pathologic complete response (pCR) rates were compared using Fisher's exact test. Rates of LRR and distant recurrence (DR) were estimated by Kaplan-Meier methods. Cox regression analysis was performed. Results: Median follow-up was 62 months (range 7-161) with 21 LRR, 84 DR and 58 deaths. pCR rate and 5-year LRR rates were 14% and 7% in the entire cohort, respectively. Significantly more TN and HER2+ patients achieved pCR than HR+ patients (Table 1, p=0.003). TN patients had higher 5-year LRR rate compared to HR+ and HER2+ patients (18% vs. 4% and 6%, p=0.02). The 5-year LRR rate was 0% in pCR patients versus 9% in non-pCR patients (p=0.06). In patients without pCR, TN subtype was associated with increased LRR (23% at 5-year vs. 4% HR+ and 7% HER2+; p=0.001). TN patients without pCR were also associated with increased DR (48% at 5-year vs. 29% HR+ and 30% HER2+, p=0.02). On univariate analysis, TN subtype (HR=2.0, p=0.008), pathologic stage (HR=2.2, p=0.02), and pN+ status (HR=9.3, p=0.03) were associated with increased LRR. Conclusions: Although response to NAC strongly correlates with breast cancer subtype, patients with HR+ and HER2+ breast cancer had favorable rates of LRR regardless of response to NAC, perhaps because of additional postoperative targeted therapy. In contrast, while no LRR was seen in TN patients with pCR, those with poor response to NAC had significantly higher LRR risk, underscoring the need for potential new treatment strategies to improve local control in this population. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12623-e12623
Author(s):  
Osama Mosalem ◽  
Saud Alsubait ◽  
Shouq Kherallah ◽  
Venumadhavi Gogineni ◽  
Ling Wang ◽  
...  

e12623 Background: Hematologic markers have been looked at as potential prognostic biomarkers in a variety of cancers. Ni and colleagues (2014) have shown that an elevated pre-treatment lymphocyte-to-monocyte ratio (LMR) was significantly associated with improved disease-free survival (DFS) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NACT). Given the prognostic implications of hematologic inflammatory parameters, we sought to understand if such biomarkers will predict response to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Methods: We conducted a retrospective review of breast cancer patients treated with NACT at our institution (2008-2018). Data on patient characteristics, stage, pathologic characteristics, and blood counts were collected. Blood parameters prior to NACT were used to calculate LMR and neutrophil-to-lymphocyte ratio (NLR). To test the impact of LMR and NLR on pathologic response, a two sample mean test was used first as univariate analysis. Next, logistic regression was employed for multivariate analysis controlling for patient characteristics with interaction of LMR and NLR with ER, PR and HER2 status. Results: A total of 50 patients were included. 38% of patients achieved a pathologic complete response (pCR). The mean LMR was 3.69 (1.4-12.5), and the mean NLR was 2.55 (0.66 – 9.31). On univariate analysis, a high NLR was associated with a higher likelihood of achieving a pCR (OR = 1.64, 95% CI = 1.01-2.63). A high LMR was associated with a higher likelihood of pCR; however, this was not statistically significant (OR = 1.08, 95% CI = 0.78-1.47). On multivariate analysis, patients with HER-2 positive disease with a high LMR had a significantly higher chance of having a pCR (OR = 1.72, 95% CI = 1.06-2.78). Conclusions: Our study showed that NLR was a predictor of pCR in breast cancer patients receiving neoadjuvant chemotherapy. A high NLR was associated with achieving a pCR on univariate analysis. Multivariate analysis suggested that HER-2 positive disease with a high LMR had a significantly higher chance of achieving a pCR. The results of this cohort correlate with previous reports by others showing that pre-NACT LMR and NLR provide prognostic information in patients with breast cancer. Although limited by sample size, this adds to the growing body of literature supporting peripheral blood counts as a biomarker for outcomes in breast cancer.


2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 90-90
Author(s):  
Sushma Agrawal ◽  
Punita Lal ◽  
Shaleen Kumar ◽  
Gaurav Agarwal ◽  
Anjali Mishra ◽  
...  

90 Background: Breast cancer patients commonly present in locally advanced stage (LABC) in our country. We propose to correlate the pathological response to neoadjuvant chemotherapy (NACT) and its impact on survival based on the intrinsic subtypes. Methods: Consecutive patients of LABC who underwent NACT (taxane and or anthracyclines based )followed by definitive surgery and radiotherapy during the period January 2007 to December 2012 were grouped on the basis of intrinsic subtypes (Luminal A, Luminal B, Her-2 Type, Basal). The pathological response to NACT in tumour as well as axillary nodes [complete response (pCR), partial response (pPR)] was correlated with the disease free survival (DFS) and overall survival (OS) at 5 years in the intrinsic subtypes using Kaplan Meier Analysis. Results: Among 208 patients the median age was 46 years (range 24-81 years), 46% premenopausal,54% postmenopausal, presenting tumour and node stage was 15% T2, 40% T3, 45% T4,8% N0, 42% N1, 41% N2, 9% N3.The intrinsic subtypes at presentation were Luminal A (16%), Luminal B (23%), Her-2 Type (23%), Basal (37%).The pCR rate in node was significantly higher in Her-2 type and Basal subtype (Table ). At a median followup of 34 months (range 6-84 mo)the 5 year DFS and OS was significantly higher in patients achieving pCR tumour or node in Her-2 type and Basal subtype (Table ). Conclusions: The pCR rate to NACT in tumour or node seems to be considerably higher in our population than that reported in the western literature. pCR (tumour and node) is a surrogate for both DFS and OS at 5 years in Her-2 and basal subtypes of breast cancer. [Table: see text]


2018 ◽  
Vol 25 (5) ◽  
pp. 1535-1545 ◽  
Author(s):  
Aura Muntasell ◽  
Federico Rojo ◽  
Sonia Servitja ◽  
Carlota Rubio-Perez ◽  
Mariona Cabo ◽  
...  

2010 ◽  
Vol 28 (11) ◽  
pp. 1821-1828 ◽  
Author(s):  
Abigail S. Caudle ◽  
Ana M. Gonzalez-Angulo ◽  
Kelly K. Hunt ◽  
Ping Liu ◽  
Lajos Pusztai ◽  
...  

Purpose Although most breast cancer patients who receive neoadjuvant chemotherapy (NCT) have a tumor response, a small proportion experience progressive disease (PD). Predictors of response have been reported, but predictors for progression have not been identified. We sought to identify predictors of tumor progression during NCT with the ultimate aim of identifying patients who might benefit from a first-line surgical approach or from novel targeted therapies. Patients and Methods Data were obtained from reviewing medical records of patients with stage I to III breast cancer who received NCT (anthracycline and/or taxane based). Statistical analysis was performed to compare patients with any response or stable disease with patients with PD. Results One thousand nine hundred twenty-eight patients received NCT; 1,762 patients (91%) had some response, 107 (6%) had stable disease, and 59 (3%) had PD at some point during NCT. Factors predictive of PD included African American race (P = .002), tumor (T) status (P = .002), and American Joint Committee on Cancer clinical stage (P = .02). Histopathologic features of PD were high tumor grade (P = .005), high Ki-67 score (P = .002), and negative estrogen receptor (ER)/progesterone receptor (PR) status (P < .001/P < .001). Pre-NCT T status, race, and ER status were independent predictors of progression in multivariate analysis. Disease progression was a negative predictor of distant disease–free survival and overall survival in multivariate analysis (P < .001). Conclusion Factors predictive of PD include race, advanced tumor stage, high nuclear grade, high Ki-67 score, and ER/PR negativity. Because many of these variables are also associated with response to NCT, novel molecular predictors are needed to identify patients at risk for progression on standard NCT.


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