scholarly journals Biomarker dynamics and prognosis in breast cancer after neoadjuvant chemotherapy

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Cristina Zarotti ◽  
Bärbel Papassotiropoulos ◽  
Constanze Elfgen ◽  
Konstantin Dedes ◽  
Denise Vorburger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Tumor Biology ◽  
Tumor Stage ◽  
Treatment Modalities ◽  
Proliferation Index ◽  
Prognostic Impact ◽  
Intrinsic Subtypes ◽  
Significant Difference

AbstractBreast cancer is a biologically diverse disease with treatment modalities selected based on tumor stage and tumor biology. Distinct intrinsic subtypes and surrogate biomarker profiles play a major role for therapeutic decisions. Response rates to systemic and local treatments as well as the interaction with epidemiological risk factors have been validated in clinical trials and translational studies. This retrospective study addresses the question how biomarker profiles and treatment modalities in the neoadjuvant chemotherapy setting have changed during the past 15 years and what prognostic impact these changes implicate. 342 female breast cancer stage I-IV patients receiving neoadjuvant chemotherapy between 2003 and 2017 were analyzed. Overall survival (OS) was correlated with preoperative clinical stage, postoperative pathological stage, treatment modalities and tumor biology before and after chemotherapy. Two subgroups were separated using an arbitrary cut-off year at 2009/2010, due to 2010 when platinum containing regimens were first administered. Median follow-up was 54 months. 57 (17%) patients died; recurrences occurred in 103 of 342 (30%) patients. Nodal stage and intrinsic subtypes (pre- and postoperative) significantly correlated with OS (p < 0.001). Preoperative histological grading lacked prognostic power. When comparing the patient characteristics of the subgroups, we found significant difference in the following characteristics: cT, ypT, ypN, pCR and chemotherapy regimens (p < 0.001). There was no difference in OS when comparing the two subgroups. Pathological complete response (pCR) rates had a significant impact on OS and disease-free survival (DFS) in HER2+ and triple negative subtypes (p = 0.03). In multivariate analysis, high proliferation index (> 30%), clinical metastatic stage and pathological tumor stage had prognostic impact on OS (p < 0.001, p = 0.0001, p = 0.002). Clinico-pathological factors and distinct therapy regiments especially in triple negative and HER2+ subtypes have prognostic impact on pCR, OS and DFS after neoadjuvant chemotherapy.

scholarly journals Prognostic Impact of Stromal Immune Infiltration before and after Neoadjuvant Chemotherapy (NAC) in Triple Negative Inflammatory Breast Cancers (TNIBC) Treated with Dose-Dense Dose-Intense NAC

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2657
Author(s):  
Luca Campedel ◽  
Paul Blanc-Durand ◽  
Asker Bin Asker ◽  
Jacqueline Lehmann-Che ◽  
Caroline Cuvier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Dose Dense ◽  
The Impact

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.

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

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11566-e11566
Author(s):  
S. Koya ◽  
Y. Li ◽  
S. A. McDaniel ◽  
A. F. LoBuglio ◽  
H. Krontiras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Triple Negative ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Free Survival ◽  
Significant Difference ◽  
Grade 3 ◽  
Dose Dense

e11566 Background: NSABP B-18 randomized women with operable breast cancer to receive chemotherapy (AC) either pre- or postoperatively; in the study there was no significant difference in disease free survival (DFS) or overall survival (OS) among patients in either group. Pathologic complete response rate (pCR) was directly proportional to DFS and OS. Dose dense adjuvant chemotherapy (ATC) has shown a statistically significant improvement in DFS and OS. Methods: We performed a single institution review of pts enrolled in a neoadjuvant trial and who received dose dense neoadjuvant chemotherapy (doxorubicin 60 mg/m2 IV Q2wks x4, paclitaxel 175 mg/m2 IV Q2wks x4, and cyclophosphamide 600 mg/m2 IV Q2wks x4) to assess response rates, safety, and DFS. Women with newly diagnosed breast cancer, T ≥ 3cm, any N, M0 were enrolled. Results: Since 02/2003, 43 pts were enrolled (mean age 47.6, range 28–64) and received dose dense chemotherapy. 41.4% of the pts were triple negative and 14.6% were Her2+ by FISH or IHC. The median follow-up is 49 months (range 8–69). Two patients dropped out without finishing therapy. Forty one pts completed dose dense chemotherapy and proceeded to surgery. 17 pts (41.4%) achieved a pCR in the breast and of those 14 pts were also negative in the axillary lymph nodes (34.1% pCR in the breast and lymph nodes). 10 of the 17 pts with pCR in the breast (8 out of the 14 pts with pCR in breast and axillary lymph nodes) were triple negative. 18 pts (43.9%) achieved PR, 3 pts (7.31%) had SD and 3 pts (7.31%) had PD. Up to November 2008, 7 pts who did not have a pCR have relapsed (4 triple negative, 1 Her2+, 1 ER/PR positive and 1 ER negative, PR positive) with a relapsed free survival rate of 85%. Hematologic toxicity consisted of grade 3 anemia in 2 patients with no grade 4 anemia, no G4 thrombocytopenia and febrile neutropenia in 2 pts. Non-hematologic grade 3 or 4 toxicity consisted of mediport thrombosis in 2 pts, hyperglycemia in 2 pts, syncope in 1 pt, neuropathy in 1 pt, and varicella zoster in 1 pt. Conclusions: Our results show that dose dense neoadjuvant chemotherapy achieves a pCR (breast + node) in about 1/3 of patients (34%) with tolerable toxicity; although the number of patients is limited, our data suggest that triple negative breast cancer seems to be the most sensitive tumor to this regimen. No significant financial relationships to disclose.

Differential pathologic complete response rates after neoadjuvant chemotherapy among molecular subtypes of triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1005-1005 ◽  
Author(s):  
Hiroko Masuda ◽  
Keith A. Baggerly ◽  
Ying Wang ◽  
Ya Zhang ◽  
Ana M. Gonzalez-Angulo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Gene Profiling ◽  
Intrinsic Subtypes ◽  
Subtype Classification ◽  
Tnbc Subtype

1005 Background: By gene profiling, Lehmann et al. (J Clin Invest 121:2750-2767, 2011) reported that triple-negative breast cancer (TNBC) can be classified into 6 clusters—basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), and luminal androgen receptor (LAR)—plus an unstable (UNS) cluster. While it is clear that patients with TNBC differently respond to chemotherapy, the clinical relevance of these molecular TNBC subtypes is unknown. Methods: We qualitatively reproduced the Lehmann et al. experiments using Affymetrix CEL files from the public datasets. We identified 130 TNBC gene expression microarrays obtained from 03/00 to 03/10. All patients had received neoadjuvant chemotherapy containing sequential taxane and anthracycline-based regimens and had evaluable pathological tumor response data. Median follow-up was 68.1 months. (5.1-147.5). We classified TNBC samples using Lehmann’s gene signatures, then performed Fisher's exact test to correlate TNBC subtype and pCR status. To assess the independent utility of TNBC subtype for predicting pCR status, we fit a logistic regression model to our data and used age, clinical stage, treatment regimens, and nuclear grade as potential explanatory factors. We also performed comparison of the subtypes with the PAM50 intrinsic subtypes and RCB index. Results: The BL1 subtype had the highest pCR rate (52%); BL2 and LAR the lowest (0% and 10%, respectively). TNBC subtype and pCR status were significantly associated (p = 0.044). TNBC subtype was an independent predictor of pCR status (p = 0.022) by a likelihood ratio test.The Lehmann’s subtype classification better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like). Conclusions: Dividing TNBC into 7 subtypes predicts high vs. low pCR rate. The 7-subtype classification may lead to innovative personalized medicine strategies for patients with TNBC. There is a need for prospective validation of the hypothesis that pCR rates associated with the seven TNBC subtypes will predict long-term patient outcome.

scholarly journals Apoptotic Index Fails to Predict Chemoresponse in Breast Cancer

2019 ◽  
Vol 2 (2) ◽  
pp. 55-60
Author(s):  
Kamal Basri Siregar
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Response ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Apoptotic Index ◽  
Chemotherapy Response ◽  
Significant Difference ◽  
Before And After ◽  
Kidney Liver

The responsiveness of neoadjuvant chemotherapy in Triple Negative Breast Cancer (TNBC) needs determination to prevent overtreatment with chemoresistance regimen. A total of 60 consented patients from Haji Adam Malik and Bunda Thamrin Hospital were included in this cohort prospectie study. Patients with heart, kidney, liver disease, history of surgery, chemotherapy, or hormonal therapy were excluded. Apoptotic indexes were taken from all subjects before and after neoadjuvant chemotherapy. After 3 cycles of neoadjuvant chemotherapy, 31 subjects (51.7%) did not show clinical response while 29 subjects (48.3%) had clinical response. There was no significant difference of apoptotic index before and after neoadjuvant chemotherapy (5.47+1.38 vs 5.52+1.08 pg/mL). There was also no significant relationship between apoptosis index and clinical response (p=0.993). This study showed that apoptotic index fails to be neoadjuvant chemotherapy response predictor in triple negative breast cancer. Further research with larger samples is needed to confirm this result

scholarly journals Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

2020 ◽  
Author(s):  
Takaaki Oba ◽  
Kazuma Maeno ◽  
Daiya Takekoshi ◽  
Mayu Ono ◽  
Tokiko Ito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Prognostic Nutritional Index ◽  
Prognostic Impact ◽  
Nutritional Index ◽  
Significant Difference ◽  
Before And After ◽  
The Mean

Abstract Background: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).Methods: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. Results: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). Conclusions: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

scholarly journals Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

2020 ◽  
Author(s):  
Takaaki Oba ◽  
Kazuma Maeno ◽  
Daiya Takekoshi ◽  
Mayu Ono ◽  
Tokiko Ito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Prognostic Nutritional Index ◽  
Prognostic Impact ◽  
Nutritional Index ◽  
Significant Difference ◽  
Before And After ◽  
The Mean

Abstract Background: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Methods: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. Results: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01) . The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). Conclusions: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

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]

Outcomes of patients with triple-negative breast cancer treated with radiation therapy.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 88-88
Author(s):  
Siddhartha Yadav ◽  
Maha Saada Jawad ◽  
Jessica Wobb ◽  
J. Ben Wilkinson ◽  
Dhiraj Yadav ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Stage ◽  
Treatment Modalities ◽  
Breast Cancers ◽  
Breast Irradiation ◽  
Radiation Group

88 Background: This study compares outcomes between different types of loco-regional treatment modalities used in patients with triple negative breast cancers. Methods: 299 patients with triple negative breast cancer diagnosed between April 2004 and August 2011 at a single institution and who were treated with radiation therapy were included in an IRB-approved retrospective review. Electronic charts were reviewed for demographic and pathologic data as well as outcome data including locoregional and distant recurrence. The median follow up period was 3 years. 200 (70%) patients underwent lumpectomy with whole breast irradiation (WBI). 68 (22.7%) patients received mastectomy and radiation while 31(10.4%) patients were treated with lumpectomy with accelerated partial breast irradiation (APBI). Results: Forty-nine patients (16.4%) experienced recurrence (10 local; 6 contralateral; 3 regional; 36 distant). There was a significant (p<0.0001) difference in the proportion of patients that experienced a recurrence in each treatment group: 34% (n=23) in mastectomy with radiation group; 12% (n=23) in lumpectomy with WBI group; 10% (n=3) in lumpectomy with APBI group. On univariate analysis, tumor size, tumor stage, nodal stage, overall stage, total number of positive nodes, total number of nodes removed, and whether or not the patients had an axillary lymph node dissection were significantly associated with recurrence (p<0.05). When these predictor variables, including treatment type, were examined using a stepwise cox proportional hazards regression model for recurrence, the only variables that remained significant were tumor stage (p= 0.0003) and the number of positive nodes (p= 0.0008). Survival curves were significantly different (p = 0.016) between the lumpectomy with WBI group and the mastectomy with radiation group. Over all follow-up times, the probability of survival was smallest for the mastectomy with radiation group. Conclusions: The recurrence pattern for triple negative breast cancers treated with radiation therapy was primarily distant for all treatment modalities. In our patient population, tumor stage and number of positive lymph nodes predicted for recurrence while radiotherapy technique did not.

scholarly journals 6q deletion is frequent but unrelated to patient prognosis in breast cancer

Breast Cancer ◽  
2021 ◽  
Author(s):  
Patrick Lebok ◽  
Hannah Bönte ◽  
Martina Kluth ◽  
Christina Möller-Koop ◽  
Isabell Witzel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Stage ◽  
Proliferation Index ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Advanced Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Advanced Tumor ◽  
Frequent Event

Abstract Background Deletions involving the long arm of chromosome 6 have been reported to occur in breast cancer, but little is known about the clinical relevance of this alteration. Methods We made use of a pre-existing tissue microarray with 2197 breast cancers and employed a 6q15/centromere 6 dual-labeling probe for fluorescence in situ (FISH) analysis Results Heterozygous 6q15 deletions were found in 202 (18%) of 1099 interpretable cancers, including 19% of 804 cancers of no special type (NST), 3% of 29 lobular cancers, 7% of 41 cribriform cancers, and 28% of 18 cancers with papillary features. Homozygous deletions were not detected. In the largest subset of NST tumors, 6q15 deletions were significantly linked to advanced tumor stage and high grade (p < 0.0001 each). 6q deletions were also associated with estrogen receptor negativity (p = 0.0182), high Ki67 proliferation index (p < 0.0001), amplifications of HER2 (p = 0.0159), CCND1 (p = 0.0069), and cMYC (p = 0.0411), as well as deletions of PTEN (p = 0.0003), 8p21 (p < 0.0001), and 9p21 (p = 0.0179). However, 6q15 deletion was unrelated to patient survival in all cancers, in NST cancers, or in subsets of cancers defined by the presence or absence of lymph-node metastases. Conclusion Our data demonstrate that 6q deletion is a frequent event in breast cancer that is statistically linked to unfavorable tumor phenotype and features of genomic instability. The absence of any prognostic impact argues against a clinical applicability of 6q15 deletion testing in breast cancer patients.

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