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12 pages, 1404 KiB

Open AccessArticle

Patterns of Recurrence after Neoadjuvant Therapy in Early Breast Cancer, according to the Residual Cancer Burden Index and Reductions in Neoadjuvant Treatment Intensity

by Christoph Suppan, Florian Posch, Hannah Deborah Mueller, Nina Mischitz, Daniel Steiner, Eva Valentina Klocker, Lisa Setaffy, Ute Bargfrieder, Robert Hammer, Hubert Hauser, Philipp J. Jost, Nadia Dandachi, Sigurd Lax and Marija Balic

Cancers 2021, 13(10), 2492; https://doi.org/10.3390/cancers13102492 - 20 May 2021

Cited by 9 | Viewed by 3887

Abstract

Background: The prognostic performance of the residual cancer burden (RCB) score is a promising tool for breast cancer patients undergoing neoadjuvant therapy. We independently evaluated the prognostic value of RCB scores in an extended validation cohort. Additionally, we analyzed the association between chemotherapy [...] Read more.

Background: The prognostic performance of the residual cancer burden (RCB) score is a promising tool for breast cancer patients undergoing neoadjuvant therapy. We independently evaluated the prognostic value of RCB scores in an extended validation cohort. Additionally, we analyzed the association between chemotherapy dose reduction and RCB scores. Methods: In this extended validation study, 367 breast cancer patients with available RCB scores were followed up for recurrence-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). We also computed standardized cumulative doses of anthracyclines and taxanes (A/Ts) to investigate a potential interaction between neoadjuvant chemotherapy dose reduction and RCB scores. Results: Higher RCB scores were consistently associated with adverse clinical outcomes across different molecular subtypes (HR for RFS = 1.60, 95% CI 1.33–1.93, p < 0.0001; HR for DDFS = 1.70, 95% CI 1.39–2.05, p < 0.0001; HR for OS = 1.67, 95% CI 1.34–2.08, p < 0.0001). The adverse impact prevailed throughout 5 years of follow-up, with a peak for relapse risk between 1–2 years after surgery. Clinical outcomes of patients with RCB class 1 did not differ substantially at 5 years compared to RCB class 0. A total of 180 patients (49.1%) underwent dose reduction of neoadjuvant A/T chemotherapy. We observed a statistically significant interaction between dose reduction and higher RCB scores (interaction p-value = 0.042). Conclusion: Our results confirm RCB score as a prognostic marker for RFS, DDFS, and OS independent of the molecular subtype. Importantly, we show that lower doses of cumulative neoadjuvant A/T were associated with higher RCB scores in patients who required a dose reduction. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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17 pages, 1074 KiB

Open AccessArticle

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

by Beatriz Grandal, Manon Mangiardi-Veltin, Enora Laas, Marick Laé, Didier Meseure, Guillaume Bataillon, Elsy El-Alam, Lauren Darrigues, Elise Dumas, Eric Daoud, Anne Vincent-Salomon, Laure-Sophie Talagrand, Jean-Yves Pierga, Fabien Reyal and Anne-Sophie Hamy

Cancers 2021, 13(4), 746; https://doi.org/10.3390/cancers13040746 - 11 Feb 2021

Cited by 15 | Viewed by 2819

Abstract

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid [...] Read more.

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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11 pages, 559 KiB

Open AccessArticle

The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

by Toshiaki Iwase, Aaroh Parikh, Seyedeh S. Dibaj, Yu Shen, Tushaar Vishal Shrimanker, Sudpreeda Chainitikun, Kumiko Kida, Maryanne E. Sapon, Onur Sahin, Anjali James, Andrea Yizel Delgado Medrano, Ann H. Klopp and Naoto T. Ueno

Cancers 2021, 13(4), 608; https://doi.org/10.3390/cancers13040608 - 4 Feb 2021

Cited by 11 | Viewed by 2397

Abstract

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment [...] Read more.

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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14 pages, 1337 KiB

Open AccessArticle

HER2-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens

by Enora Laas, Arnaud Bresset, Jean-Guillaume Féron, Claire Le Gal, Lauren Darrigues, Florence Coussy, Beatriz Grandal, Lucie Laot, Jean-Yves Pierga, Fabien Reyal and Anne-Sophie Hamy

Cancers 2021, 13(3), 370; https://doi.org/10.3390/cancers13030370 - 20 Jan 2021

Cited by 5 | Viewed by 2595

Abstract

Background: No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against HER2-positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the prognosis of HER2-positive BC patients treated with NAC to that [...] Read more.

Background: No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against HER2-positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the prognosis of HER2-positive BC patients treated with NAC to that of patients treated with adjuvant chemotherapy (AC). Materials and methods: We retrospectively analyzed disease-free (DFS) and overall survival (OS) in 202 HER2-positive patients treated with NAC and 701 patients treated with AC. All patients received trastuzumab in addition to chemotherapy. Patient data were weighted by a propensity score to overcome selection bias. Results: After inverse probability of treatment weights (IPTW) adjustment, no difference in DFS (p = 0.3) was found between treatments for the total population. However, after multivariate analysis, an interaction was found between cN status and chemotherapy strategy (IPTW-corrected corrected Hazard ratio cHR = 0.52, 95% CI (0.3–0.9), p_interaction = 0.08) and between menopausal status and chemotherapy (CT) strategy (cHR = 0.35, 95%CI (0.18–0.7)) p_interaction < 0.01). NAC was more beneficial than AC strategy in cN-positive patients and in postmenopausal patients. Moreover, after IPTW adjustment, the multivariate analysis showed that the neoadjuvant strategy conferred a significant OS benefit (cHR = 0.09, 95%CI [0.02–0.35], p < 0.001). Conclusion: In patients with HER2-positive BC, the NAC strategy is more beneficial than the AC strategy, particularly in cN-positive and postmenopausal patients. NAC should be used as a first-line treatment for HER2-positive tumors. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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12 pages, 809 KiB

Open AccessArticle

The Presence of an In Situ Component on Pre-Treatment Biopsy Is Not Associated with Response to Neoadjuvant Chemotherapy for Breast Cancer

by Julie Labrosse, Charlotte Morel, Thanh Lam, Enora Laas, Jean-Guillaume Feron, Florence Coussy, Marick Lae, Fabien Reyal and Anne-Sophie Hamy

Cancers 2021, 13(2), 235; https://doi.org/10.3390/cancers13020235 - 10 Jan 2021

Cited by 7 | Viewed by 2477

Abstract

A ductal in situ (DCIS) component is often associated with invasive breast carcinoma (BC), and its effect on response to treatment is unknown. We assessed the predictive value of the DCIS component for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). We analyzed [...] Read more.

A ductal in situ (DCIS) component is often associated with invasive breast carcinoma (BC), and its effect on response to treatment is unknown. We assessed the predictive value of the DCIS component for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). We analyzed a cohort of 1148 T1–3NxM0 breast cancer (BC) patients treated by NAC at Institut Curie between 2002 and 2012. The presence of a DCIS component was retrospectively recorded from both the pre-NAC biopsy pathological report and surgical specimens. We included 1148 BC patients treated by NAC for whom pre- and post-NAC data concerning the in situ component were available. DCIS was present before NAC in 19.6% of the population. Overall, 283 patients (19.4%) achieved pCR after NAC. There was no significant association between the presence of DCIS on pre-NAC biopsy and pCR. In a multivariate analysis including subtype, tumor size, grade, mitotic index, and Ki67 index, only BC subtype (luminal/TNBC/HER2-positive) and Ki67 were significantly associated with pCR. The presence of a DCIS component on pre-NAC biopsy is not associated with pCR and does not seem to be a critical factor for predicting response to NAC. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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20 pages, 891 KiB

Open AccessArticle

The Prognostic Value of Lymph Node Involvement after Neoadjuvant Chemotherapy Is Different among Breast Cancer Subtypes

by Lucie Laot, Enora Laas, Noemie Girard, Elise Dumas, Eric Daoud, Beatriz Grandal, Jean-Yves Pierga, Florence Coussy, Youlia Kirova, Elsy El-Alam, Guillaume Bataillon, Marick Lae, Florence Llouquet, Fabien Reyal and Anne-Sophie Hamy

Cancers 2021, 13(2), 171; https://doi.org/10.3390/cancers13020171 - 6 Jan 2021

Cited by 8 | Viewed by 2505

Abstract

Introduction: The three different breast cancer subtypes (Luminal, HER2-positive, and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype. [...] Read more.

Introduction: The three different breast cancer subtypes (Luminal, HER2-positive, and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype. Methods: We retrospectively evaluated the axillary involvement (0, 1 to 3 positive nodes, ≥4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into three classes (0; 1 to 3; 4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes. Results: 1197 patients were included in the analysis (luminal (n = 526, 43.9%), TNBCs (n = 376, 31.4%), HER2-positive BCs (n = 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (P_interaction = 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR 2.8; 95% CI [1.93; 4.06], p < 0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR = 1.24, 95% CI = [0.86; 1.79]). In patients with TNBC, both 1-3N+ and ≥4 N+ classes were associated with a decreased RFS (HR = 3.19, 95% CI = [2.05; 4.98] and HR = 4.83, 95% CI = [3.06; 7.63], respectively versus ypN0, p < 0.001). Similar decreased prognosis were observed among patients with HER2-positive BC (1-3N +: HR = 2.7, 95% CI = [1.64; 4.43] and ≥4 N +: HR = 2.69, 95% CI = [1.24; 5.8] respectively, p = 0.003). Conclusion: The prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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13 pages, 1092 KiB

Open AccessArticle

Circulating Tumor Cells and Bevacizumab Pharmacokinetics during Neoadjuvant Treatment Combining Chemotherapy and Bevacizumab for Early Breast Cancer: Ancillary Analysis of the AVASTEM Trial

by Renaud Sabatier, Jean-Yves Pierga, Hervé Curé, Rakan Abulnaja, Eric Lambaudie, François-Clément Bidard, Jean-Marc Extra, Patrick Sfumato and Anthony Gonçalves

Cancers 2021, 13(1), 140; https://doi.org/10.3390/cancers13010140 - 5 Jan 2021

Cited by 5 | Viewed by 3153

Abstract

The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics [...] Read more.

The phase II AVASTEM trial explored the impact of chemotherapy-bevacizumab combination on breast cancer stem cells in the neoadjuvant setting. We aimed to identify biological features associated with preoperative chemotherapy efficacy and prognosis by analyses of circulating tumor cells (CTCs) and bevacizumab pharmacokinetics (PK). The main objective was to assess the prognostic (relapse-free survival and overall survival) and predictive (pathological complete response, pCR) values of CTCs (CellSearch technology) and bevacizumab PK (ELISA). Seventy-five patients were included. Out of them 50 received bevacizumab-chemotherapy and 25 received chemotherapy alone. CTC results were available for 60 patients and PK data for 29 patients in the experimental arm. The absence of CTC at inclusion was correlated to better outcome. Five-years overall survival (OS) was 91% for CTC-negative patients vs. 54% for CTC-positive cases (HR = 6.21; 95%CI (1.75–22.06), p = 0.001, log-rank test). Similar results were observed for RFS with 5 y-RFS of 78% vs. 44% (HR = 3.51; 95%CI (1.17–10.52), p = 0.017, log-rank test). However, CTC status at baseline was not predictive of pCR (p = 0.74). CTC status after one cycle was not a significant prognostic factor (HR = 1.56; 95%CI (0.19–12.67); p = 0.68 for OS and HR = 2.76; 95%CI (0.60–12.61); p = 0.17 for RFS, log-rank test). Bevacizumab serum levels could not predict pCR and survival. PK values were not associated with treatment-related toxicities. In conclusion, CTCs detection at baseline is a prognostic marker for breast cancer receiving a neoadjuvant chemotherapy-bevacizumab combination independently of tumor response. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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26 pages, 1801 KiB

Open AccessArticle

Impact of BRCA Mutation Status on Tumor Infiltrating Lymphocytes (TILs), Response to Treatment, and Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

by Beatriz Grandal, Clémence Evrevin, Enora Laas, Isabelle Jardin, Sonia Rozette, Lucie Laot, Elise Dumas, Florence Coussy, Jean-Yves Pierga, Etienne Brain, Claire Saule, Dominique Stoppa-Lyonnet, Sophie Frank, Claire Sénéchal, Marick Lae, Diane De Croze, Guillaume Bataillon, Julien Guerin, Fabien Reyal and Anne-Sophie Hamy

Cancers 2020, 12(12), 3681; https://doi.org/10.3390/cancers12123681 - 8 Dec 2020

Cited by 16 | Viewed by 3348

Abstract

Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA status. Material [...] Read more.

Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA status. Material and Methods: Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline BRCA pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses. Results: Among 1199 BC patients: 46 were BRCA-deficient and 221 BRCA-proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in BRCA-deficient BC (p = 0.001), and this association remained statistically significant only in the luminal BC subtype (p = 0.006). The interaction test between BC subtype and BRCA status was nearly significant (P_interaction = 0.056). Pre and post-NAC TILs were not significantly different between BRCA-deficient and BRCA-proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in BRCA-deficient BC. Survival analysis were not different between BRCA-carriers and non-carriers. Conclusions: BRCA mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. BRCA-carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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15 pages, 1961 KiB

Open AccessArticle

No Impact of Smoking Status on Breast Cancer Tumor Infiltrating Lymphocytes, Response to Neoadjuvant Chemotherapy and Prognosis

by Vanille Simon, Lucie Laot, Enora Laas, Sonia Rozette, Julien Guerin, Thomas Balezeau, Marion Nicolas, Jean-Yves Pierga, Florence Coussy, Marick Laé, Diane De Croze, Beatriz Grandal, Judith Abecassis, Elise Dumas, Florence Lerebours, Fabien Reyal and Anne-Sophie Hamy

Cancers 2020, 12(10), 2943; https://doi.org/10.3390/cancers12102943 - 12 Oct 2020

Cited by 4 | Viewed by 2262

Abstract

Tobacco use is associated with an increase in breast cancer (BC) mortality. Pathologic complete response (pCR) rate to neoadjuvant chemotherapy (NAC) is influenced by tumor-infiltrating lymphocyte (TIL) levels and is associated with a better long-term survival outcome. The aim of our study is [...] Read more.

Tobacco use is associated with an increase in breast cancer (BC) mortality. Pathologic complete response (pCR) rate to neoadjuvant chemotherapy (NAC) is influenced by tumor-infiltrating lymphocyte (TIL) levels and is associated with a better long-term survival outcome. The aim of our study is to evaluate the impact of smoking status on TIL levels, response to NAC and prognosis for BC patients. We retrospectively evaluated pre- and post-NAC stromal and intra tumoral TIL levels and pCR rates on a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012 at Institut Curie. Smoking status (current, ever, never smokers) was collected in clinical records. We analyzed the association between smoking status, TIL levels, pCR rates and survival outcomes among the whole population, and according to BC subtype. Nine hundred and fifty-six BC patients with available smoking status information were included in our analysis (current smokers, n = 179 (18.7%); ever smokers, n = 154 (16.1%) and never smokers, n = 623 (65.2%)). Median pre-NAC TIL levels, pCR rates, or median post-NAC TIL levels were not significantly different according to smoking status, neither in the whole population, nor in any BC subtype group. With a median follow-up of 101.4 months, relapse-free survival (RFS) and overall survival (OS) were not significantly different by smoking status. We did not find any significant effect of tobacco use on pre- and post-NAC TILs nor response to NAC. Though our data seem reassuring, BC treatment should still be considered as a window of opportunity to offer BC patients accurate smoking cessation interventions. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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12 pages, 677 KiB

Open AccessArticle

Tissue Immune Profile: A Tool to Predict Response to Neoadjuvant Therapy in Triple Negative Breast Cancer

by Bruna Cerbelli, Simone Scagnoli, Silvia Mezi, Alessandro De Luca, Simona Pisegna, Maria Ida Amabile, Michela Roberto, Lucio Fortunato, Leopoldo Costarelli, Angelina Pernazza, Lidia Strigari, Carlo Della Rocca, Paolo Marchetti, Giulia d’Amati and Andrea Botticelli

Cancers 2020, 12(9), 2648; https://doi.org/10.3390/cancers12092648 - 16 Sep 2020

Cited by 16 | Viewed by 3008

Abstract

Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated [...] Read more.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) can predict better survival outcomes in patients with early triple negative breast cancer (TNBC). Tumor infiltrating lymphocytes (TILs), Programmed Death-Ligand 1 (PD-L1), and Cluster of Differentiation 73 (CD73) are immune-related biomarkers that can be evaluated in the tumor microenvironment. We investigated if the contemporary expression of these biomarkers combined in a tissue immune profile (TIP) can predict pCR better than single biomarkers in TNBC. Tumor infiltrating lymphocytes (TILs), CD73 expression by cancer cells (CC), and PD-L1 expression by immune cells (IC) were evaluated on pre-NACT biopsies. We defined TIP positive (TIP+) as the simultaneous presence of TILS ≥ 50%, PD-L1 ≥ 1%, and CD73 ≤ 40%. To consider the effects of all significant variables on the pCR, multivariate analysis was performed. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used for model selection. We retrospectively analyzed 60 biopsies from patients with TNBC who received standard NACT. Pathological complete response was achieved in 23 patients (38.0%). Twelve (20.0%) cases resulted to be TIP+. The pCR rate was significantly different between TIP+ (91.7%) and TIP− (25.0%) (p < 0.0001). Using a multivariate analysis, TIP was confirmed as an independent predictive factor of pCR (OR 49.7 (6.30–392.4), p < 0.0001). Finally, we compared the efficacy of TIP versus each single biomarker in predicting pCR by AIC and BIC. The combined immune profile is more accurate in predicting pCR (AIC 68.3; BIC 74.5) as compared to single biomarkers. The association between TIP+ and pCR can be proposed as a novel link between immune background and response to chemotherapy in TNBC, highlighting the need to consider an immunological patients’ profile rather than single biomarkers. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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14 pages, 1306 KiB

Open AccessArticle

Survival in Cytologically Proven Node-Positive Breast Cancer Patients with Nodal Pathological Complete Response after Neoadjuvant Chemotherapy

by Hitoshi Inari, Natsuki Teruya, Miki Kishi, Rie Horii, Futoshi Akiyama, Shunji Takahashi, Yoshinori Ito, Takayuki Ueno, Takuji Iwase and Shinji Ohno

Cancers 2020, 12(9), 2633; https://doi.org/10.3390/cancers12092633 - 15 Sep 2020

Cited by 2 | Viewed by 2570

Abstract

Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. Methods: We retrospectively reviewed the data [...] Read more.

Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. Methods: We retrospectively reviewed the data of patients with cytologically proven axillary node-positive disease who received NAC and those with axillary pN- without NAC for control between January 2007 and December 2012. We compared outcomes according to response in the axilla to NAC and between patients with axillary pCR and matched pairs with axillary pN- without NAC using propensity scores. Results: We included 596 patients with node-positive breast cancer who received NAC. The median follow-up period was 64 months. Patients with axillary pCR showed significantly better distant disease-free survival (DDFS) and overall survival (OS) than patients with residual axillary disease (both p < 0.01). There was no significant difference in DDFS and OS between patients with axillary pCR and matched pairs with axillary pN- without NAC. Conclusion: Axillary pCR was associated with improved prognosis. Patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes. This information will be useful when considering the intensity of follow-up and adjuvant therapy. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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14 pages, 4447 KiB

Open AccessArticle

No Difference in Overall Survival and Non-Breast Cancer Deaths after Partial Breast Radiotherapy Compared to Whole Breast Radiotherapy—A Meta-Analysis of Randomized Trials

by Jan Haussmann, Wilfried Budach, Stefanie Corradini, David Krug, Balint Tamaskovics, Edwin Bölke, Freddy-Joel Djiepmo-Njanang, Ioannis Simiantonakis, Kai Kammers and Christiane Matuschek

Cancers 2020, 12(8), 2309; https://doi.org/10.3390/cancers12082309 - 17 Aug 2020

Cited by 12 | Viewed by 3291

Abstract

Purpose/objective: Adjuvant radiotherapy after breast conserving surgery is the standard approach in early stage breast cancer. However, the extent of breast tissue that has to be targeted with radiation has not been determined yet. Traditionally, the whole breast was covered by two opposing [...] Read more.

Purpose/objective: Adjuvant radiotherapy after breast conserving surgery is the standard approach in early stage breast cancer. However, the extent of breast tissue that has to be targeted with radiation has not been determined yet. Traditionally, the whole breast was covered by two opposing tangential beams. Several randomized trials have tested partial breast irradiation (PBI) compared to whole breast irradiation (WBI) using different radiation techniques. There is evidence from randomized trials that PBI might result in lower mortality rates compared to WBI. We aimed to reassess this question using current data from randomized trials. Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect sizes for overall survival (OS), breast cancer-specific survival (BCSS), and non-breast cancer death (NBCD) as investigated endpoints. Analysis of subgroups using different radiation techniques was intended. We used hazard ratios (HR) and risk differences (RD) to estimate pooled effect sizes. Statistical analysis was performed using the inverse variance heterogeneity model. Results: We identified eleven studies randomizing between PBI and WBI. We did not find significant differences in OS (n = 14,070; HR = 1.02; CI-95%: 0.89–1.16; p = 0.810, and n = 15,203; RD = −0.001; CI-95%: −0.008–0.006; p = 0.785) and BCSS (n = 15,203; RD = 0.001; CI-95%: −0.002–0.005; p = 0.463). PBI also did not result in a significant decrease of NBCD (n = 15,203; RD = −0.003; CI-95%: −0.010–0.003; p = 0.349). A subgroup analysis by radiation technique also did not point to any detectable differences. Conclusion: In contrast to a previous assessment of mortality, we could not find a detrimental effect of WBI on OS or NBCD. A longer follow-up might be necessary to fully assess the long-term mortality effects of PBI compared to WBI. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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Review

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18 pages, 781 KiB

Open AccessReview

Neoadjuvant Endocrine Therapy in Breast Cancer Management: State of the Art

by Florence Lerebours, Luc Cabel and Jean-Yves Pierga

Cancers 2021, 13(4), 902; https://doi.org/10.3390/cancers13040902 - 21 Feb 2021

Cited by 10 | Viewed by 5246

Abstract

Endocrine therapy is the mainstay of treatment in HR+/HER2- breast cancers, which represent about 70% of all breast cancers. Neoadjuvant therapy has been developed since the 1990s to address several issues, including breast-conserving surgery (BCS) and improvement of survival rates. For a long [...] Read more.

Endocrine therapy is the mainstay of treatment in HR+/HER2- breast cancers, which represent about 70% of all breast cancers. Neoadjuvant therapy has been developed since the 1990s to address several issues, including breast-conserving surgery (BCS) and improvement of survival rates. For a long time, neoadjuvant endocrine therapy (NET) was confined to frail patients in order to improve surgery outcome. Since the 2000s, NET now plays a central role as a research tool for predictive endocrine sensitivity biomarkers and targeted therapies. One of the major issues in early HR+/HER2- breast cancer is to identify patients in whom chemotherapy can be safely withheld. In vivo assessment of response to NET might be the best treatment strategy to address this issue. Full article

(This article belongs to the Special Issue Neoadjuvant Systemic Therapy in Early Breast Cancer)

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