End Of Neoadjuvant Chemotherapy Research Articles

Time to surgery after neoadjuvant chemotherapy in breast cancer and its impact on survival in a middle-income country.

e12640 Background: The time to surgery after neoadjuvant chemotherapy (NACT) in breast cancer and its impact on survival has not been sufficiently evaluated in low- or middle-income countries. The objective of this study was to analyze the impact on overall survival in a cancer hospital in Guayaquil, Ecuador. Methods: This is a retrospective study carried out at the SOLCA Guayaquil Hospital in Ecuador from January 2009 to December 2011. The inclusion criteria were women ≥18 years old, diagnosed with invasive breast cancer in stages II and III, who were treated with NACT followed by surgery. The data were collected from clinical records; those with incomplete data were excluded, and the variables age, stage, lymphovascular invasion (LVI), and pathological response were included. Survival was grouped into <8 and ≥8 weeks for the comparative analysis. Survival time was calculated from diagnosis by biopsy until death; A p-value of ˂0.05 was taken as significant; The Kaplan-Meier estimate was used for overall survival, then the groups were compared by Log Rank, and the influence of the covariates was estimated in the Cox regression model. The data were analyzed in an SPSS v29 statistical program. Results: 200 patients were identified, 195 of whom had all the information for the analysis. The median time between the end of NACT and surgery was 7.57 weeks (range, 2.43-29.14 weeks). In the < 8 and ≥ 8 weeks group, there were 111 and 84 patients, respectively. The clinical characteristics are described in the Table. The median overall survival in the entire cohort was 8.32 years (CI: 6.68-9.96), and for the < 8 and ≥ 8 weeks groups, it was 10.0 and 6.56 years, respectively, with a Log-Rank of 0.031. The follow-up (median) of the entire cohort was 7.54 years (range 0.63 – 10.99 years). The multivariate Cox regression showed that LVI, HR: 2.35 p<0.001; clinical stage III (II vs III), HR: 2.47 p<0.001; residual disease (pathological complete response vs residual disease), HR: 2.70 p=0.012; age ≤ 50 years (≤ 50 years vs > 50 years), HR: 1.69 p=0.011; were factors that statistically contributed to worse survival, however, the time between the end of NACT and surgery < 8 and ≥ 8 weeks (p = 0.07) had no statistical impact on survival. Nonetheless, a numerical trend towards better survival was noted in the < 8 week group. Conclusions: The delay in time to surgery after NACT had a negative trend in survival, although it was not statistically significant, which may be due to the small sample size. [Table: see text]

Survival and inferential analysis in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and subsequent sentinel lymph node biopsy: prospective single-center study

BackgroundThe lymph node staging is the major prognostic factor in breast cancer patients. Sentinel lymph node biopsy (SLNB) allows an exactly axillar staging in patients with early disease, but not in locally advance breast cancer (LABC). Our aim was to study, the feasibility and accuracy of the SLNB technique with and without axillar lymphadenectomy (LDN) and with lymph node clipping after neoadjuvant chemotherapy (NAC), in patients with LABC.Patients and methodsPatients diagnosed with LABC, scheduled for NAC and subsequent surgery and SLNB. Subsequently the patients were scheduled for adjuvant chemotherapy/hormonotherapy and radiotherapy according with the postsurgical results. Main end points were overall survival (OS) disease-free survival (DFS), mortality, SLNB identification rate (IR), sensitivity, false negative rate (FNR) of SLNB versus LDN, negative predictive value (NPV) and overall accuracy.ResultsOur IR with different techniques was between 89.9 and 100%. OS was between 89 and 97%. DFS was between 89.8 and 96.8%. Sensitivity was between 75 and 100%. NPV was between 89.6 and 100%. FNR was between 0 and 25%; and accuracy was between 66 and 72%. We found that survival was lower (p < 0.05) in patients with triple negative and Luminal B/HER2 intrinsic subtype; with progression or major partial response in Magnetic Resonance Imaging (MRI) results at the end of NAC and in patients with BRCA1/2 mutation.ConclusionsOur study presents excellent results of SLNB alone in patients with LABC with complete nodal response with an OS and DFS > 95%. The FNR is very high in partial responders, so we cannot recommend the SLNB alone in LABC. We recommend, in cN+ patients, axillar clipping, SLNB and LDN because in more than 50% of the patients with axillar clipping, this was not found, and because in 36% of the patients with negative LDN, the SLN (Sentinel Lymph Node) obtained was the only positive node, so these techniques together decrease the FNR and improve the node staging, OS and DFS. This study is the first prospective study that assess OS and DFS in patients with LABC, all submitted to SLNB.

Abstract PO4-22-09: Impact of time to surgery after neoadjuvant chemotherapy on pCR rate in locally-advanced breast cancer

Abstract Objective: Neoadjuvant chemotherapy along with surgical treatment are the important parts of treatment for locally advanced breast cancer. Extending the interval between the end of neoadjuvant chemotherapy and surgery may decrease tumor response in patients with locally advanced breast cancer. However, data if timing of surgery after neoadjuvant therapy affect the Pathologic complete response (pCR) rate is controversial. Materials and methods: We performed a retrospective analysis of 874 consecutive patients with IIIA-IIIC breast cancer that received neoadjuvant chemotherapy and surgery between 2000 and 2020 in N.N. Blokhin National Cancer Research Center. The median interval between the last injection of chemotherapy and surgery was 30 days (range 10 to 95 days). The variables were compared using log-rank statistics and Cox regression model. Results. Pathologic complete response (pCR) was registered in 250 (31,4%) patients. Univariate analysis showed that extending the interval between the end of neoadjuvant chemotherapy and surgery for each day were associated with decrease of probability of pCR (OR 0,982; p = 0,009). Patients with triple-negative and ER-/HER2+ achieved higher rates of pCR compared to luminal A subtype (p&amp;lt; 0,0001). Tumor grade, tumor size, Ki67 were independent predictive factors for tumor pCR (p &amp;lt; 0,001). Multivariate analysis also showed an independent negative effect of the time interval before surgery on the achieving pCR. Then the patients were stratified into three cohorts according to the time of surgery after neoadjuvant chemotherapy: &amp;lt; 22 days, 22-42 days, or &amp;gt;42 days. The odds ratio (OR) for pCR was 1 for &amp;lt; 22 days (reference), 0,833 for 22-42 days (p=0,332) and 0,576 for ≥43 days (p=0,033). Cox regression model demonstrated that the interval between the end of neoadjuvant chemotherapy and surgery (more than 42 days), tumor size, triple-negative and ER-/HER2+ were the significant predictive factors for pCR. Tumor grade, tumor size and age of patients were not independent predictive factors for in-breast pCR. Conclusion: Our study showed improved pCR if surgery was performed within 6 weeks after the end of neoadjuvant chemotherapy in locally advanced breast cancer. Results of multivariate logistic regression analysis to assess the probability of achieving complete pathomorphological regression Results of multivariate logistic regression analysis to assess the probability of achieving complete pathomorphological regression Citation Format: Alexander Petrovskiy, Viktory Amosova, Oxana Trofimova, Mona Frolova, Anastasya Soloshenko, Alexey Rumyantsev. Impact of time to surgery after neoadjuvant chemotherapy on pCR rate in locally-advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-22-09.

Abstract PO1-18-11: Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC

Abstract Background: In the UK, triple-negative breast cancer (TNBC) comprises 10-15% of breast cancer diagnoses annually. TNBC represents a clinical challenge due to a lack of expression of three treatable drug targets, namely oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2). The mainstay of treatment involves the use of neoadjuvant chemotherapy (NACT) followed by surgical excision where up to 50% of patients will achieve a pathological complete response (pCR). The addition of neo-adjuvant immunotherapy may increase the pCR rate to 60%. The presence of lymphatics and blood vessels within/around malignant tumours plays a role in cancer progression as does the formation of new blood vessels (angiogenesis). The vascular endothelial growth factor (VEGF) family and their receptors (VEGFRs) play an important role in angiogenesis as well as promoting the growth and survival of cancer cells. VEGFR is frequently overexpressed in TNBC and promotes changes in vascular endothelial cells, the basement membrane and the surrounding extracellular matrix. Co-expression of epidermal growth factor receptor (EGFR) and VEGFR enhances tumour growth and angiogenesis in an autocrine and paracrine manner. An alternate mechanism for tumour microcirculation in tumours is vasculogenic mimicry (VM). This is distinct from classical tumour angiogenesis. The presence of VM is associated with poor overall survival in breast cancer patients and anti-angiogenic treatment of TNBC may even promote tumour growth, proliferation and metastasis by stimulating VM. Conventional imaging techniques such as B-mode ultrasound and MRI are commonly used to monitor disease response in the breast but have limited accuracy in predicting pCR or residual disease. High-resolution contrast-enhanced ultrasound (HRCEUS) may offer a more accurate test to monitor TNBC response to NACT. This method utilises intravenously injected microbubbles, which consist of a gas core with an outer shell of lipid/albumin to image tumour microvasculature as well as gross tumour morphology. Trial Design: Single-centre study to evaluate HRCEUS to image the microvasculature of TNBC tumours in patients undergoing (NACT) and correlate imaging results with established markers of angiogenesis, proliferation and vasculogenic mimicry. Eligibility Criteria: Female, 18 to 60 years, histologically confirmed invasive TNBC with planned NACT, able to consent and in the Investigator’s opinion, adhering to the trial recommendations and governance. Aims: To investigate if imaging changes in the tumour microvasculature indicate a response to NACT and are reflected in the expression of proliferative markers. To determine whether changes in the tumour microvasculature and disease response are driven by angiogenesis +/- VM. To investigate whether overall disease response and changes in the microvasculature are influenced by the basal type phenotype or germline mutations in BRCA 1/2. Investigate patient satisfaction with the contrast ultrasound test. Statistical Methods: Quantify HRCEUS imaging characteristics of microvasculature at 3 treatment points. Compare this with the results of conventional imaging and the histopathological results of surgical excision at the end of NACT. Quantify immunohistochemical markers of angiogenesis, proliferation and VM at three treatment points and compare this with HRCEUS. Determine phenotype of all cases using immunohistochemistry to identify the basal Perform subtype analysis to assess if the basal phenotype is associated with imaging and immunohistochemical changes in the microvasculature during NACT. Test patients for germline BRCA1/2 gene mutations. Perform subtype analysis to assess if germline BRCA1/2 mutations are associated with imaging and immunohistochemical changes in the microvasculature during NACT. Present accrual (2 patients) and target accrual (5 patients) Contact details: j.rait@nhs.net Citation Format: Jaideep Rait, Michelle Garrett, Catherine Harper-Wynne, Sonia Saw, Mengxing Tang, Priya Palanisamy, Matthieu TOULEMONDE, Karina Cox. Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-11.

Abstract PO2-14-04: Circulating tumor DNA after neoadjuvant chemotherapy is a better prognostic test than Residual Cancer Burden in patients with triple negative breast cancer and residual tumor

Abstract Background The presence of residual tumor at surgery (non-pathological complete response or non-pCR) occurs in about half of TNBCs treated with neoadjuvant chemotherapy (NAC) signals chemoresistance. Although the addition of further adjuvant chemotherapy (Capecitabine/Xeloda) significantly improves RFS in these patients, the majority of patients nevertheless have a good prognosis, and thus may not require adjuvant Capecitabine. One of the best prognostic biomarkers in these patients is Residual Cancer Burden (RCB), which relies on the pathological examination of the residual tumor bed and lymph nodes obtained at surgery. Circulating tumor DNA (ctDNA) is a plasma-based biomarker, which has been shown to accurately detect minimal residual disease in breast cancer. We have previously shown that detection of ctDNA after NAC but before surgery in patients with non-pCR signals very poor prognosis, while non-detectable ctDNA is associated with an excellent prognosis. We now compare ctDNA to RCB score in TNBC patients with non-pCR. Methods In the multicenter TRICIA study, 44 TNBC patients with non-pCR after NAC in 5 hospital centers had consented to serial plasma collection prior to and after surgery. RCB score was calculated from pathology records. Whole exome sequencing (WES) was performed on DNA extracted from primary tumor biopsies or residual tumors at surgery to identify tumor-specific mutations (5 variants/patient). Digital droplet PCR (ddPCR) assays were developed for these mutations and tests were run in an academic hospital setting. Patients with at least one detectable mutation were considered ctDNA positive for a given time point. The detection of ctDNA was correlated with relapse-free survival (RFS). Results: The median follow up was 40 months. 19 of the 44 patients relapsed within 2 years after surgery. Detection of ctDNA at the end of NAC but before surgery (T1) was correlated with very poor RFS (H.R. = 0.15, p&amp;lt; 0.0001 (95% CI = 0.067-0.35)). 14/15 patients (93%) without detectable ctDNA did not recur, while 76% of patients with detectable ctDNA relapsed. The RCB score distribution was as follows: 7 RCB1, 21 RCB2 and 16 RCB3. According to RCB score, 1/7 RCB1, 11/21 RCB2 and 11/16 RCB3 patients relapsed. All but one of the relapsed patients had detectable ctDNA in at least one timepoint. All 11 RCB3 patients that relapsed had detectable ctDNA while none of the 5 RCB3 patients without relapse had detectable ctDNA. The one RCB1 patient with detectable ctDNA also relapsed. In cox regression analysis, the lack of ctDNA detection was significantly associated with excellent RFS in RCB2 (HR=0.16, p=0.003, (95% CI=0.05-.53)) and RCB3 groups (HR=0.10, p=0.0005, 95% CI= 0.03-.36). Conclusion ctDNA testing using ddPCR in an academic hospital-based setting at the post-NAC time point identifies an excellent prognostic group in TNBC patients with non-pCR and can discriminate very good from very poor prognosis in both RCB2 and RCB3 score subgroups. The detection of ctDNA may be superior to RCB scores in assessing prognosis in patients with non-pCR. Citation Format: Mark Basik, Talia Roseshter, Anna Klemantovich, Luca Cavallone, Adriana Aguilar-Mahecha, Josiane Lafleur, Cathy Lan, Oluwadara Elebute, Sarah Jenna, Jean-Francois Boileau, Manuela Pelmus. Circulating tumor DNA after neoadjuvant chemotherapy is a better prognostic test than Residual Cancer Burden in patients with triple negative breast cancer and residual tumor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-04.

Association between alteration of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, cancer antigen-125 and surgical outcomes in advanced stage ovarian cancer patient who received neoadjuvant chemotherapy

IntroductionOptimal resection significantly influences the prognosis of advanced-stage epithelial ovarian cancer (EOC) patients undergoing debulking surgery. In patients who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), the determination of the ideal timing for surgery remains a challenge. Inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and CA-125 levels, have been recognized as potential predictive markers. ObjectiveThis study aims to evaluate the predictive value of changes in NLR, PLR, and CA-125 levels following NACT, specifically assessing their impact on surgical outcomes during IDS for advanced-stage EOC. MethodsA retrospective cohort study enrolled advanced-stage EOC patients who underwent NACT followed by IDS at Vajira Hospital in Thailand from January 2009 to June 2023. Data on clinical, surgical, and inflammatory markers were collected, and the predictive value of these markers for suboptimal resection outcomes was assessed. ResultsAmong the 65 patients, 98.5 % exhibited radiologic responses post-NACT, while 29.2 % experienced suboptimal resections. Univariate analysis did not reveal significant associations between suboptimal resection and NLR changes after the first NACT cycle or alterations in NLR, PLR, and CA-125 levels at the end of NACT. Subsequent analysis suggested that an NLR decrease exceeding 70 % after the first cycle and NACT completion might predict suboptimal resection, yet statistical analyses showed limited prognostic efficacy (AuROC = 0.608 and 0.597). ConclusionOur study does not support that changes in NLR, PLR, platelet count, and CA-125 levels after NACT reliably predict IDS outcomes. Additional prospective investigations using larger cohorts or a combination of evaluation methods, rather than relying solely on NLR, are recommended.

The role of neoadjuvant chemotherapy in patients with primary resectable pancreatic cancer: A retrospective cohort study

Background. Currently available data on the efficacy and indications for neoadjuvant chemotherapy in patients with primary resectable pancreatic cancer are contradictory and not clearly defined.&#x0D; Aim. To conduct a comparative assessment of the effectiveness of neoadjuvant chemotherapy and primary surgical treatment followed by adjuvant chemotherapy in patients with primary resectable pancreatic cancer.&#x0D; Materials and methods. In our study, the efficacy of neoadjuvant chemotherapy was retrospectively evaluated in 45 patients and in 153 patients with primary surgical treatment and subsequent adjuvant chemotherapy.&#x0D; Results. With a median follow-up of 41.7 months. Both, recurrence free survival in the group of patients receiving neoadjuvant chemotherapy followed by surgical treatment (n=33; 73%) and in the group with surgical treatment and subsequent adjuvant chemotherapy (13.9 and 19.5 months; p=0.35) and overall survival (28.4 months vs 33.7 months; p=0.29) were no different. The CA level of 19.9500 IU/ml in the neoadjuvant chemotherapy group was observed in 20 (44.4%) patients. At the same time, surgical treatment was performed only in 11 (55%) patients. At the same time, at the CA 19.9 level 500 IU/ml, at the end of neoadjuvant chemotherapy, surgical treatment was not performed in only 3 (12%) patients (p=0.005).&#x0D; Conclusion. The long-term results of treatment of patients with primary resectable pancreatic cancer, whose first stage was neoadjuvant chemotherapy, practically do not differ from the group whose treatment began with surgery. Treatment of patients with an initially high (500 IU/ml) level of CA 19.9 is preferable to start with neoadjuvant chemotherapy. Patients who may have doubts about the likelihood of adjuvant chemotherapy (general condition, social adaptation, place of residence), it is also preferable to start treatment with neoadjuvant chemotherapy. It is necessary to change the algorithm of examination of patients, especially those with a level of CA 19.9500 IU/ml, to exclude a greater prevalence, for example, performing diagnostic laparoscopy to exclude metastases in the peritoneum.

Abstract P4-07-40: Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy

Abstract Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p&amp;lt; 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p&amp;lt; 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p&amp;lt; 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p&amp;lt; 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

Abstract P2-11-26: The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor

Abstract Background The presence of residual tumour at surgery (non-pathological complete response or non-pCR) occurs in about half of TNBCs treated with neoadjuvant chemotherapy (NAC) and signals chemoresistance and poor prognosis. Although further adjuvant chemotherapy (Capecitabine/Xeloda) results in improved survival in patients with non-pCR, only about 15% of such patients do benefit. Circulating tumor DNA (ctDNA) is a plasma-based biomarker that can be used to reveal real-time data about the disease and treatment progression. We have previously shown that detection of ctDNA after NAC signals poor prognosis. To validate and extend our previous results using an academic hospital-based tumor bespoke assay, we performed ctDNA measurements in non-pCR TNBC patients at the pre-operative, post-operative, 3 and 6-month time points. Methods Whole exome sequencing (WES) was performed on residual tumors from 34 TNBC patients to identify tumour-specific mutations (5/patient). Digital droplet PCR (ddPCR) assays were developed for these mutations and performed as per our previous work. Patients with at least one detectable mutation were considered ctDNA positive for a given time point. The detection of ctDNA was correlated with relapse-free survival (RFS). Results The overall RFS was 44%, with 56 % of patients received adjuvant Xeloda. Detection of ctDNA at the end of NAC (T1) correlated with poor prognosis of RFS (n = 33, p-value = 0.009, HR = 0.29 (95% CI = 0.12 to 0.74)). Detection of ctDNA after surgery (T2) and while on Xeloda (T3) showed no significant prognostic value for RFS. However, ctDNA detection at the 6-month time point, after Xeloda treatment (T4), showed stronger prognostic value for RFS (n = 17, p-value = 0.004, HR = 0.12 (95% CI = 0.03 to 0.51)). When measuring changes in ctDNA detectability from T1 to T4, 4 patients initially positive became ctDNA negative after the 6-month interval, and only 1 of these 4 had a relapse, compared with 10 of 11 that remained positive at the 6-month time point (p = 0.01, Chi-squared test). 3 of the 4 patients that cleared their ctDNA had received Xeloda. In addition, 2 patients initially negative became ctDNA positive at the 6-month time point (T4) and both relapsed, compared with only 1 of 5 that remained negative at 6 months (p = 0.035, Chi-squared test). For patients who received adjuvant Xeloda ctDNA positivity at T1 was associated with a worse RFS (p-value = 0.028, HR = 3.3884 (95% CI = 1.160 to 13.00)). Conclusion ctDNA testing using ddPCR in an academic hospital-based context at the post-NAC time point as well as at 6 months after surgery identifies an excellent prognostic group in TNBC patients with non-pCR and changes in ctDNA during the adjuvant period have prognostic value. This personalized approach to treatment management is ready for prospective testing in patients who have undergone NAC and require additional chemotherapy. Citation Format: Talia Roseshter, Anna Klemantovich, Luca Cavallone, Adriana Aguilar-Mahecha, Josiane Lafleur, Oluwadara O. Elebute, Sarah Jenna, Jean-Francois Boileau, Manuela Pelmus, Mark Basik, Cathy Lan. The prognostic role of circulating tumor DNA after neoadjuvant chemotherapy in triple negative breast cancer with residual tumor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-26.

Insights from Bacterial 16S rRNA Gene into Bacterial Genera and Predicted Metabolic Pathways Associated with Stool Consistency in Rectal Cancer Patients: A Proof of Concept.

To examine if gut microbial taxa abundances and predicted functional pathways correlate with Bristol Stool Form Scale (BSFS) classification at the end of neoadjuvant chemotherapy and radiation therapy (CRT) for rectal cancer. Rectal cancer patients (n = 39) provided stool samples for 16S rRNA gene sequencing. Stool consistency was evaluated using the BSFS. Gut microbiome data were analyzed using QIIME2. Correlation analysis were performed in R. At the genus level, Staphylococcus positively correlates (Spearman's rho = 0.26), while Anaerofustis, Roseburia, Peptostreptococcaceae unclassified, Ruminococcaceae UBA1819, Shuttleworthia, Ca. Soleaferrea, Anaerostignum, Oscillibacter, and Akkermansia negatively correlate with BSFS scores (Spearman's rho -0.20 to -0.42). Predicted pathways, including mycothiol biosynthesis and sucrose degradation III (sucrose invertase), were positively correlated with BSFS (Spearman's rho = 0.03-0.21). The data support that in rectal cancer patients, stool consistency is an important factor to include in microbiome studies. Loose/liquid stools may be linked to Staphylococcus abundance and to mycothiol biosynthesis and sucrose degradation pathways.

Interval time between neoadjuvant chemotherapy and surgery in advanced gastric cancer doesn't affect outcome: A meta analysis.

The efficacy of neoadjuvant chemotherapy for advanced gastric cancer is not yet firmly confirmed, but the exciting results demonstrated in several clinical studies have led neoadjuvant chemotherapy as the important treatment methods in guidelines. The 4-6 weeks interval time is currently the most commonly used in clinical treatment, but there are insufficient studies to support this time and the optimal interval has not yet been identified. The aim of this meta-analysis was to investigate the short-term life quality and long-term prognostic impact of the interval time between the end of neoadjuvant chemotherapy and surgery in patients with advanced gastric cancer. We conducted a systematic literature search in PUBMED, Embase and Cochrane Liabrary for studies published or reported in English from January 2006 to May 2022. We summarised relevant studies for the time to surgery (TTS), included as retrospective studies and prospective studies. The primary study outcome was the rate of pathological complete response (pCR), and the secondary outcomes included R0 resection rate, incidence of serious postoperative complications, 3-year progression free survival time (PFS) rate and overall survival time (OS) rate. TTS were classified in three groups: 4-6 weeks, <4 weeks and >6 weeks. The ratio ratios (ORs) were calculated and forest plots and funnel plots were made to analysis by using fixed-effect and random-effect models in Review Manager 5.2. A total of five studies included 1,171 patients: 411 patients in shorter TTS group (<4 weeks), 507 patients in medium TTS group (4-6 weeks) and 253 patients in longer TTS groups (>6 weeks). And The results of our meta-analysis indicate that there are no significant difference between the three groups. The pCR, R0 resection rate, incidence of serious postoperative complications, 3-year PFS and OS were similar between three groups. Although there many studies exploring the suitable TTS in advanced gastric cancer, but we have not find the evidence to prove the TTS is the risk factor influencing the outcome. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022369009.

Muscle mass loss in breast cancer patients of reproductive age (≤ 45years) undergoing neoadjuvant chemotherapy.

Loss of muscle mass is associated with negative clinical outcome in breast cancer (BC) patients. Therefore, the aim of the study is to evaluate if there is pectoralis muscle area (PMA) depletion, reflecting loss of muscle mass, in breast cancer patients of reproductive age (≤ 45years) undergoing neoadjuvant chemotherapy (NAC) and to correlate PMA with clinical and histopathological data. This monocentric study, approved by our institutional review board, enrolled a total of 52 consecutive patients (mean age 37 ± 4.96years) with histologically proven primary breast cancer between January 2019 and September 2021, treated with NAC and in whom tumor response and PMA were assessed with breast MRI. Two radiologists calculated PMA before and after NAC independently and blindly on axial 3D FLASH pre-contrast T1-weighted images. Wilcoxon-Mann-Whitney U test compared median values and percentage changes of pectoralis muscle area at the beginning and at the end of NAC (158 ± 25.5days). Multivariate regression analysis on ΔPMA (difference between PMA pre-NAC and PMA post-NAC) was done according to clinical and histopathological data. Inter-reader and intra-reader agreement was estimated with K statistics. Pre-NAC PMA mean value was larger than post-NAC PMA mean value (9.6 ± 2.6cm2 vs. 8.7 ± 2.2cm2, p < 0.001, delta value 1.41). According to the RECIST criteria, no significant differences between complete and partial response were found. Multivariate regression analysis did not show any significant relationships between ΔPMA and age, time between MRI examinations, estrogen and progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 expression, lymph node involvement, RECIST criteria, histological type, and different regimes of NAC. Inter-reader (k = 0.74) and intra-reader agreement (0.67 and 0.73) in PMA assessment was good. PMA variation in BC young patients, directly estimated on breast MRI, could be a potential tool to monitor body composition during NAC with potential implications in improving outcome.

Comprehensive characterization of RNA cargo of extracellular vesicles in breast cancer patients undergoing neoadjuvant chemotherapy.

Extracellular vesicles (EVs) are g7aining increased attention as carriers of cancer-derived molecules for liquid biopsies. Here, we studied the dynamics of EV levels in the plasma of breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC) and explored the relevance of their RNA cargo for the prediction of patients' response to the therapy. EVs were isolated from serial blood samples collected at the time of diagnosis, at the end of NAC, and 7 days, 6, and 12 months after the surgery from 32 patients with locally advanced BC, and 30 cancer-free healthy controls (HCs) and quantified by nanoparticle tracking analysis. The pre-treatment levels of EVs in BC patients were higher than in HCs, significantly increased during the NAC and surgery, and decreased to the levels found in HCs 6 months after surgery, thus showing that a substantial fraction of plasma EVs in BC patients are produced due to the disease processes and treatment. RNA sequencing analysis revealed that the changes in the EV levels were associated with the alterations in the proportions of various RNA biotypes in EVs. To search for RNA biomarkers that predict response to the NAC, patients were dichotomized as responders and non-responders based on Miller-Payne grades and differential expression analyses were carried out between responders and non-responders, and HCs. This resulted in the identification of 6 miRNAs, 4 lncRNAs, and 1 snoRNA that had significantly higher levels in EVs from non-responders than responders at the time of diagnosis and throughout the NAC, and significantly lower levels in HCs, thus representing biomarkers for the prediction of response to NAC at the time of diagnosis. In addition, we found 14 RNAs representing piRNA, miRNA, lncRNA, snoRNA, and snRNA biotypes that were induced by NAC in non-responders and 2 snoRNAs and 1 piRNA that were induced by NAC in patients with early disease progression, thus warranting further functional studies on their role in chemoresistance and metastasis.

Association of serum reproductive hormones changes after neoadjuvant chemotherapy with hormone receptors expression alterations and survival outcomes in breast cancer.

PurposeThis study aimed to determine the effect of neoadjuvant chemotherapy (NAC) on circulating levels of reproductive hormones and evaluate the correlation of hormone changes after NAC with hormone receptors expression alterations and relapse-free survival (RFS) outcomes in breast cancer.MethodsInformation from 181 breast cancer patients who received NAC was retrospectively analyzed. For hormones parameters, the median and interquartile range (IQR) were provided at baseline and the end of NAC then was compared by Wilcoxon signed-rank test. Categorical variables were represented as numbers and percentages and were compared via two-sided chi-square and Fisher's tests. The RFS outcomes were compared between patients according to hormone changes using the log-rank test. Univariate and multivariate survival analyses with hazard ratios (HR) and 95% confidence intervals (95% CI) were carried out using Cox regression.ResultsSex steroids including estradiol, progesterone, testosterone, and dehydroepiandrosterone sulfate (DHEAS) levels decreased significantly after NAC among both premenopausal and postmenopausal patients (all P < 0.05). Decreased estradiol levels were associated with reduced progesterone receptor (PR) expression (P = 0.030). In multivariate survival analysis, the non-decreased progesterone level was strongly associated with worse RFS (non-decreased vs. decreased, HR = 7.178, 95% CI 2.340–22.019, P = 0.001). Patients with decreased progesterone levels exhibited better 3-year RFS compared with those with non-decreased (87.6% vs. 58.3%, log-rank, P = 0.001).ConclusionMultiple reproductive hormone levels were influenced by NAC. The change in estradiol level had a positive connection with PR expression alteration. Furthermore, an inverse association between the change in progesterone level and RFS outcomes was found. These findings may provide a theoretical basis for pre-operative endocrine therapy combined with NAC in breast cancer patients.

A complex approach to continuous cardiac monitoring of neoadjuvant chemotherapy: Observational study

A complex approach to continuous cardiac monitoring of neoadjuvant chemotherapy: Observational study

Abstract CT231: Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy

Abstract Introduction: Breast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC.Methods/Analysis: NeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link.Discussion: In this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions. Citation Format: Lidia Delrieu, Anne-Sophie Hamy, Florence Coussy, Amyn Kassara, Bernard Asselain, Juliana Antero, Paul De Villèle, Elise Dumas, Nicolas Forstmann, Julien Guérin, Judicael Hotton, Christelle Jouannaud, Maud Milder, Armand Leopold, Adrien Sedeaud, Pauline Soibinet, Jean-François Toussaint, Vincent Vercamer, Enora Laas, Fabien Reyal. Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT231.

Construction of a model for evaluating the efficacy of neoadjuvant chemotherapy for breast cancer and dynamic monitoring of ctDNA response to neoadjuvant chemotherapy.

e12600 Background: Neoadjuvant chemotherapy (NAC) is a routine treatment of choice for patients with locally advanced breast cancer. The pathological complete response (pCR) to NAC in breast cancer is closely related to a better prognosis. In addition, there have been few studies of the role of ctDNA in the dynamic monitoring of NAC, so we explored the prediction model of NAC to predict pCR and evaluated the role of ctDNA in the dynamic monitoring of NAC. Methods: A total of 269 breast cancer patients receiving NAC were enrolled, and a total of 266 tissue samples were collected. The tissue samples were sequenced using a panel covering 457 cancer-related genes to construct a pCR prediction model after NAC. A total of 267 blood samples were collected from 56 patients. Blood samples were collected at the indicated time points: before NAC (T0), after the first NAC and before cycle two (T1), during intermediate evaluation (T2), and after the end of NAC but before surgery (T3). We constructed a model to predict pCR after NAC by mutated genes and clinical factors, analyzed ctDNA of blood samples according to the mutated genes of the prediction model, and detected the dynamic monitoring role of ctDNA in NAC to predict prognosis. The median follow-up time for survival analysis was 898 days. Results: A total of 192 patients were enrolled to construct the prediction model. There were 51 patients in the additional validation set. We analysed the somatic mutations of 192 samples and constructed a predictive NAC response model including 5 SNV mutations (TP53, SETBP1, PIK3CA, NOTCH4 and MSH2), 4 CNV mutations (FOXP1-gain, EGFR-gain, IL7R-gain, and NFKB1A-gain), and 3 clinical factors (luminal A, Her2+ and Ki67). Analysing the ctDNA of 267 blood samples through a unique panel composed of 9 mutant genes in the prediction model, it was found that ctDNA positivity decreased with the passage of time during NAC, the ctDNA positive rates of ctDNA from T0, T1, T2 to T3 were 46%, 14%, 13% and 10%, respectively. According to survival data, pCR patients did not have disease progression after NAC. Among the non-pCR patients who had disease progression, the probability of non-pCR in patients with ctDNA cleared at T1, T2, and T3 was significantly lower than that in patients with uncleared ctDNA. Interestingly, patients who failed to achieve pCR but were ctDNA negative had a similar risk of metastasis and recurrence as those who achieved pCR. Finally, we found that the prediction model combined with ctDNA could predict pCR after NAC. It had high sensitivity and specificity and the AUC value reached 0.961. Conclusions: This study established a predictive model for predicting pCR after NAC. At the same time, ctDNA dynamic monitoring found that ctDNA status could predict NAC response and metastasis recurrence. Combining the prediction model and ctDNA status could better predict the NAC results.

Digital phenotyping in young breast cancer patients treated with neoadjuvant chemotherapy (the NeoFit Trial): protocol for a national, multicenter single-arm trial

BackgroundBreast cancer (BC) has particular characteristics in young women, with diagnosis at more advanced stages, a poorer prognosis and highly aggressive tumors. In NeoFit, we will use an activity tracker to identify and describe various digital profiles (heart rate, physical activity, and sleep patterns) in women below the age of 45 years on neoadjuvant chemotherapy for BC.MethodsNeoFit is a prospective, national, multicenter, single-arm open-label study. It will include 300 women below the age of 45 years treated with neoadjuvant chemotherapy for BC. Participants will be asked to wear a Withing Steel HR activity tracker round the clock for 12 months. The principal assessments will be performed at baseline, at the end of neoadjuvant chemotherapy and at 12 months. We will evaluate clinical parameters, such as toxicity and the efficacy of chemotherapy, together with quality of life, fatigue, and parameters relating to lifestyle and physical activity. The women will complete REDCap form questionnaires via a secure internet link.DiscussionIn this study, the use of an activity tracker will enable us to visualize changes in the lifestyle of young women on neoadjuvant chemotherapy for BC, over the course of a one-year period. This exploratory study will provide crucial insight into the digital phenotypes of young BC patients on neoadjuvant chemotherapy and the relationship between these phenotypes and the toxicity and efficacy of treatment. This trial will pave the way for interventional studies involving sleep and physical activity interventions.Trial registrationClinicaltrials.gov identifier: NCT05011721. Registration date: 18/08/2021.

Features of response to modern neoadjuvant chemotherapy with dual anti-HER2 blockade (trastuzumab and pertuzumab) in the patients with HER2-positive breast cancer stage II–III

Background. Neoadjuvant chemotherapy (NACT) with dual anti-HER2 blockade has become a priority in the treatment of patients with HER2+ breast cancer (BC) stages IIIII. However, the question of the accordance of various systems for assessing tumor response to NACT, as well as identifying predictor factors for achieving a complete pathomorphological response (pCR) in HER2+ BC remains open.&#x0D; Aim. To assess the accordance of various systems for assessing tumor response to neoadjuvant chemotherapy (NACT) in patients with HER2+ BC and to identify predictor factors for achieving pCR and residual cancer burden.&#x0D; Materials and methods. The study included 49 women with HER2+ BC stage IIIII, who underwent NACT with anti-HER2 blockade, followed by surgical treatment and morphological analysis of the results. The median age of the patients was 47 years; 91.8% had tumor size T2, N+ status 71.4%; tumor grade G3 73.5%, luminal and non-luminal HER2+ subtype 44.9 and 55.1% of patients, respectively. Ki6730% was observed in 93.9% of cases, the level of TILs in the tumor was 10%, 1020% and 20% in 38.1, 9.5 and 52.4% of cases, respectively. The patients received combinations of anthracyclines and taxanes or the anthracycline-free regimen of docetaxel + carboplatin; 87.8% of patients received a dual blockade of trastuzumab + pertuzumab, and 12.2% trastuzumab. After the end of NACT, all patients underwent a radical surgery (mastectomy or breast-conserving) with an assessment of the pathomorphological response, the pathomorphological stage of ypTN, and the residual cancer burden according to the RCB system.&#x0D; Results. The rate of complete pathomorphological response (tpCR/RCB-0/ypT0N0) in HER2+ BC was 61.2%; significant predictors of achieving tpCR were only 3 factors: primary operable BC stages (T13N01) the rate of tpCR was 71.4%, the level of TILs20% the proportion of tpCR reached 95.5%, and the dual anti-HER2 therapy (trastuzumab + pertuzumab) tpCR was 65.1%. Residual tumor was presented by classes RCB-I, RCB-II, RCB-III in 10.2, 24.5, 4.1%. The RCB-I class included of patients with a residual tumor less than 1.0 cm in the absence of regional lymph node involvement (80% of cases); class RCB-II was represented by the presence of a residual tumor less than 2.0 cm in combination with the absence or presence of residual metastases in 13 lymph nodes (83.4%), and class RCB-III was presented the residual tumors 2.0 cm and N12 status in 100% of cases (p0.0001).&#x0D; Conclusion. Modern NACT with dual anti-HER2 blockade (trastuzumab + pertuzumab) are highly effective the rate of tpCR is 61.2%, and in the presence of high TILs20% reaches 95.5%. Residual tumor in most cases was presented by class RCB-I or RCB-II, only 4% of patients had massive residual tumor load (class RCB-III).

Adapted Physical Activity for Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Trastuzumab Against HER2 (APACAN2): A Protocol for a Feasibility Study.

BackgroundThe standard care for HER2-positive breast cancer is chemotherapy plus a HER2-directed therapy. This can lead to treatment-induced cardiotoxicity. On the other hand, the practice of physical activity is known to improve cardiac function; thus HER2-positive breast cancer patients could draw particular benefit from physical activity during treatment. However, at the time of diagnosis for breast cancer, the majority of patients are insufficiently active according to physical activity recommendations of World Health Organisation, and it is difficult to remain or become active during the treatment. There is a lack of data in the literature on the optimal program to propose to patients to encourage them to be active during treatment. The aim of our study is to assess the feasibility of a home-based physical activity program during neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer.MethodsThe APACAN2 study is a single-centre, non-randomized interventional trial. Patients with HER2-positive breast cancer treated with anthracycline-based neoadjuvant chemotherapy and trastuzumab are eligible for enrolment. The supervised home-based physical activity program takes place during neoadjuvant chemotherapy (NACT). It combines aerobic and strengthening exercises. The primary endpoint is the proportion of patients reaching the international physical activity recommendations, i.e. 150 minutes of moderate-intensity activity per week at the end of NACT. The study started in April 2018 and seventy patients are expected to be recruited.DiscussionIn the literature, the majority of studies on practice of physical activity in breast cancer focus on adjuvant chemotherapy or on the period after the end of treatment. To the best of our knowledge, the APACAN2 study is the first to evaluate a home-based physical activity program during neoadjuvant chemotherapy for HER2-positive breast cancer.Trial Registration NumberClinicaltrials.gov: NCT02963363, registered on July 11, 2016. Identifier with the French National Agency for the Safety of Medicines and Health Products N°ID RCB 2016-A01344-47, registered in August 2016. Protocol: version 8, 24 February 2021.