Pathological complete response with neoadjuvant pembrolizumab and chemotherapy in non-metastatic triple-negative inflammatory breast cancer.

Background: Results of the KEYNOTE-522 trial established the role of immunotherapy in combination with neoadjuvant chemotherapy (NAC) for early-stage triple negative breast cancer (TNBC). In this trial, the addition of the immune checkpoint inhibitor, pembrolizumab, when used in combination with paclitaxel-carboplatin/doxorubicin-cyclophosphamide NAC achieved higher pathologic complete response (pCR) and improved event-free survival compared to NAC alone and thus, this regimen has become standard of care in this population. As the use of immunotherapy for early stage TNBC increases, it is critical to assess factors that impact treatment efficacy. Emerging data suggests antibiotic exposure may decrease rates of pCR among patients with solid cancers receiving NAC + immunotherapy, however, there is minimal data in breast cancer and there is heterogeneity in defined windows of antibiotic exposure. We therefore sought to assess the association of antibiotic exposure and window of antibiotic exposure on rates of pCR among patients with TBC treated with the KEYNOTE-522 regimen. Methods: Patients with non-metastatic TBNC who received NAC + pembrolizumab and completed breast surgery at our institution were identified. Clinicopathologic and treatment data including patient age, BMI, clinical stage, histology, chemotherapy regimen, receipt of antibiotics, number of pembrolizumab doses received, and final pathology details were collected. Pathologic complete response was defined as no residual invasive carcinoma in the breast or nodes (ypT0/isN0). Differences between the cohort of patients who did or did not receive antibiotics were assessed by Chi-squared tests. Rates of pCR were compared between those with antibiotic exposure vs none at the following time points: antibiotics concurrent with NAC + pembrolizumab, antibiotics within 30 days of first pembrolizumab dose, and antibiotics within 60 days of first pembrolizumab dose using logistic regression. Results: 42 women received NAC + pembrolizumab followed by surgery for non-metastatic TNBC from 2021-2024. Patient demographics are as follows: mean age 51 years, 90% cT2-4 tumors, 50% node positive at presentation, 93% invasive ductal histology with 7% metaplastic tumors. Overall, 20 (47.6%) patients received antibiotics concurrent with NAC + pembrolizumab, 13 (31%) within 30 days of first pembrolizumab dose, and 20 (47.6%) within 60 days of first pembrolizumab dose. There were no significant differences in age, BMI, clinical stage, tumor history, or number of pembrolizumab doses received between those who did or did not receive antibiotics. The overall pCR in the cohort was 59.5%. Rates of pCR for those who did or did not receive antibiotics concurrently with pembrolizumab were 55% vs 63.6%, p=0.6, respectively. Similarly, pCR rates for those who received antibiotics within 30- or 60- days of initiation of NAC + pembrolizumab compared to those who did not were 53.9% vs 62.1%, p=0.6 and 60% vs 59.1%, p=0.95, respectively. Conclusions: Use of antibiotics concurrently or within 30 days of initiation of NAC + pembrolizumab was associated a non-significant trend of reduced pCR among non-metastatic TNBC patients. While this series is limited due to the small patient cohort, these patterns align with data from other cancer types highlighting the need for additional study of the impact of antibiotic exposure and efficacy of immunotherapy for this high-risk patient population. Citation Format: Alexis Espinal, Crystal Taylor, Monika Burness, and Melissa Pilewskie. Association of antibiotic exposure with pathologic complete response in patients with non-metastatic triple-negative breast cancer receiving neoadjuvant chemotherapy and pembrolizumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS17-08.

Simple SummaryTriple-negative breast cancer is one of the most aggressive types of breast cancer, with limited treatment options and a high risk of recurrence. Recent studies have shown that adding pembrolizumab, a type of immunotherapy that helps the body’s immune system attack cancer, to standard chemotherapy can improve patient outcomes. However, most of this evidence comes from clinical trials, and little is known about how this treatment works in everyday clinical practice. In this study, we looked at real-world patients treated at our center to see whether the addition of pembrolizumab to chemotherapy improved outcomes and how safe and feasible it was. We found that patients who received pembrolizumab had higher rates of tumor disappearance before surgery, tolerated treatment well, and experienced manageable side effects. These results suggest that incorporating immunotherapy into standard care may help improve the survival and quality of life for patients with this challenging disease.Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted treatment options. Immunotherapy has recently emerged as a potential strategy. The addition of pembrolizumab to neoadjuvant chemotherapy, as established in the KEYNOTE-522 trial, represents a major advancement in targeted immunotherapy for TNBC. However, real-world data validating its feasibility and outcomes remain limited. This study aims to evaluate, in real-life settings, the impact of adding pembrolizumab to neoadjuvant chemotherapy on complete pathological response (pCR), recurrence-free survival (RFS), and overall survival (OS) in patients with non-metastatic TNBC. Methods: This retrospective cohort study included patients treated at King Hussein Cancer Center (KHCC) between 2015 and 2022. Among 8523 breast cancer cases, 761 were TNBC. Eligible patients had non-metastatic TNBC, received neoadjuvant therapy, and underwent surgery. The immunotherapy group included patients treated with neoadjuvant pembrolizumab (2019–2022); the no-immunotherapy group received standard neoadjuvant chemotherapy (2015–2022). Propensity score matching (1:1, nearest neighbor) was performed based on pre-treatment covariates including age, BMI, clinical stage, comorbidities, smoking, and histopathology. Pathological response, complication rates, RFS, and OS were analyzed using logistic regression and Kaplan–Meier curves with log-rank testing. Results: The matched cohort included 130 patients (65 per group). The study groups’ baseline characteristics were well-balanced between the two groups. Postoperative complication rates were similar across groups, with no significant increase in adverse events observed in the immunotherapy group. The mean lymph node positivity ratio was significantly lower in the immunotherapy group (2.2 ± 7.7 vs. 24.3 ± 33.1, p < 0.001), indicating reduced nodal burden. Pathologic complete response (pCR) was markedly higher with immunotherapy (66.2% vs. 9.2%, p < 0.001). However, survival outcomes were significantly improved with immunotherapy. At three years, RFS was markedly higher in the immunotherapy group (91.8%; 95% CI: 85.0–99.0%) compared to the no-immunotherapy group (53.8%; 95% CI: 42.8–67.8%), with a log-rank p < 0.001. Overall survival also significantly favored the immunotherapy group, with three-year OS of 87.2% versus 67.8% in no-immunotherapy group (p = 0.0015). Conclusions: Neoadjuvant pembrolizumab significantly enhances pathological response, reduces nodal involvement, and provides durable RFS and OS benefits in non-metastatic TNBC without increasing perioperative complications. This study supports incorporating immunotherapy into standard neoadjuvant regimens for TNBC patients and provides real-world evidence from a Middle Eastern tertiary cancer center.

BACKGROUND: Patients with stage III inflammatory breast cancer (IBC) are treated with tri-modality therapy consisting of neoadjuvant systemic therapy followed by modified radical mastectomy and post-mastectomy radiation therapy. Triple negative IBC (TN-IBC) is the subtype of IBC associated with the worst survival outcomes. Pathological complete response (pCR) rates after neoadjuvant chemotherapy have been historically low, with reports ranging between 13% and 42%. It is unknown if the addition of immune checkpoint inhibition to chemotherapy leads to improved pCR rate in TN-IBC as these patients were underrepresented in the seminal studies that led to the approval of chemoimmunotherapy for high-risk early-stage triple negative breast cancer (TNBC). METHODS: We conducted a retrospective analysis of patients with stage III TN-IBC who underwent breast surgery after receiving neoadjuvant chemoimmunotherapy. Patients were seen at Dana-Farber Cancer Institute (DFCI) or MD Anderson Cancer Center (MDACC). The analysis population consisted of all patients that were seen at either institution no more than 30 days after starting immunotherapy. The primary objective was the estimation of the pCR rate. An additional cohort of patients with TN-IBC treated with neoadjuvant chemotherapy and pembrolizumab while participating in the multi-institutional PELICAN trial (NCT03515798) will be added to the analysis at the time of the meeting. RESULTS: Thirty-seven patients (16 DFCI, 21 MDACC) were identified as having stage III TN-IBC and having received neoadjuvant chemoimmunotherapy. Twenty-five patients met criteria for inclusion in the analysis population. Patients in the DFCI cohort initiated treatment with chemoimmunotherapy between May 2021 and June 2022, and in the MDACC cohort between June 2021 and October 2022. Most patients were White (N=20, 80%), premenopausal (N=15, 60%) and overweight/obese (N=19, 76%). All patients received pembrolizumab-based therapy (Table 1). Among the 25 patients in the analysis population, 10 (40%) (95% CI: 21% to 61%) achieved a pCR, 6 patients experienced RCB-II and 9 RCB-III. At the time of last follow up, 84% of patients were alive. The results will be updated at the time of the meeting to include an additional cohort of 17 patients from the PELICAN trial. CONCLUSIONS: The addition of immune checkpoint inhibition to neoadjuvant chemotherapy led to a higher pCR rate in TN-IBC than most historical estimates. However this is still lower than what has been reported in TNBC in general. The investigation of novel systemic therapies is warranted in TN-IBC. Table 1. Patient characteristics and treatment received (analysis population) Citation Format: Filipa Lynce, Samuel Niman, Anthony Gonçalves, Megumi Kai, Sean Ryan, Elizabeth Troll, Rachel Layman, Antonio Giordano, Azadeh Nasrazadani, Faina Nakhlis, Jennifer Bellon, Laura Warren, Caroline Block, Susan Schumer, Anthony Lucci, Savitri Krishnamurthy, Florence Lerebours, Florence Dalenc, Christelle Levy, Thierry Petit, Marianne Leheurteur, Thomas Bachelot, Olivier Trédan, Sylvain Ladoire, Leonor Lopez Almeida, Christophe Zemmour, Sara Tolaney, Vicente Valero, François BERTUCCI, Meredith Regan, Wendy Woodward. Pathological complete response with chemotherapy and immune checkpoint inhibition in triple negative inflammatory breast cancer (TN-IBC) [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 PO2-03-06.

Correlation between baseline 18F-FDG PET/CT features and pathological complete response after neoadjuvant chemotherapy in early triple negative breast cancer

‘Small’ randomised neo-adjuvant chemotherapy trials in breast cancer reporting on pathological response: more harm than good?

Background: Triple-negative breast cancer (TNBC) is associated with high rates of early recurrence and poor prognosis. Chemotherapy remains the mainstay of treatment for early-stage TNBC in the preoperative setting. The KEYNOTE-522 recently demonstrated that adding pembrolizumab to chemotherapy significantly increases pathological complete response (pCR) rates in TNBC. However, real-world efficacy data remains limited. This study aims to evaluate the pCR rates among TNBC patients treated with neoadjuvant pembrolizumab at our Institution. Methods: We retrospectively retrieved data on patients diagnosed with stage I-III TNBC receiving neoadjuvant pembrolizumab at The Royal Marsden between June 2021 and June 2024. We collected data on patient demographics, tumour characteristics, treatment, and surgical pathology. We used simple statistics to evaluate the rate of pCR (ypT0/is, ypN0) after neoadjuvant systemic therapy. Results: Seventy-eight patients were included in the analysis. The median age at diagnosis was 49 years (interquartile range: 40-58). Most patients had clinical stage IIA at presentation (n=32, 41.0%) and invasive ductal carcinoma (n=74, 94.9%). Most tumours were grade 2 (n=65, 83.3%). Fifty-eight patients (74.3%) were able to complete the full regimen of chemotherapy. Among 20 patients discontinuing the treatment earlier, toxicity was the main reason for treatment discontinuation in 10 (50.0%). Forty-eight patients (61.5%) completed 8 cycles of pembrolizumab before surgery. Pembrolizumab was discontinued in 20 (25.2%), most commonly due to severe immune-related adverse effects in 15 patients (75.0%). Surgery involved breast-conservation in 43 patients (55.1%) and mastectomy in 35 patients (44.9 %). Nodal surgeries performed included sentinel lymph node biopsy in 43 patients (55.1%), axillary nodal clearance in 17 patients (21.8%), and targeted axillary dissection in 16 patients (20.5%). Overall, 41 patients achieved a pathologic complete response (pCR) rate (52.6%). pCR was more frequent in earlier-stage tumours: ( 100.0% [n=2] in stage I, 58.5% [n=31] in stage II, and 34.8% [n=8] in stage III) and in higher-grade tumours (36.4% [n=4] of grade 1 tumours, 55.4% [n=36] in grade 2 tumours, and 50% [n=1] in grade 3 tumours). pCR was achieved by 40 patients with ductal tumours (97.6%) versus 1 (2.4%) patient with other histology types pCR was seen in 29 patients who completed the planned course of chemotherapy (50%) versus 12 patients who did not (60%), and in 26 patients who completed the planned 8 cycles of pembrolizumab (54.2%) versus 15 of those who did not (50%). However, no statistically significant association was found between pCR and clinical stage, tumour grade /histology, number of chemotherapy or number of pembrolizumab cycles received (p = 0.05). Conclusion: In our analysis, the addition of pembrolizumab to chemotherapy resulted in similar pCR rates compared with published evidence. These findings reinforce the role of immunotherapy in early TNBC.. Further analyses with longer follow-up are warranted to evaluate the impact of pCR on survival in the real world. Citation Format: C. A. Chigbo, K. Udeogu, F. Sheima, N. Chukwuma, A. Khan, S. Redana, S. Mcgrath, A. Ring, S. Johnston, N. Battisti. Pathologic complete response rates after neoadjuvant chemotherapy and pembrolizumab in patients with triple negative breast cancer treated at the Royal Marsden:A retrospective analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-13.

Background Inflammatory breast cancers (IBC) particularly triple negative (TN) subtype have poor prognosis. There are few series reporting IBC outcome according to their immunohistochemical profile. We have already shown the efficiency of dose dense dose intense chemotherapy in triple negative breast cancer (1). We report a series of TNIBC treated with dose dense anthracycline cyclophosphamide followed with taxane and analyzed the correlation between pathological complete response (pCR), pre and post NAC TIL, post NAC LVI and disease free survival (DFS). Methods Between January 2010 and December 2016, all patients with TNIBC seen at breast cancer disease center, St Louis hospital, Paris, France, were treated with neoadjuvant dose dense dose intense Cyclophophamide (1.2g/m2 d1) - Epirubicin (75mg/m2 d1) q2w (SIM regimen) followed with 12 injections of paclitaxel (80 mg/m2) qw or 4 injections of docetaxel (100 mg/m2) q3w. All patients have histologically proven TN tumors and no evidence of metastases assessed by initial FDG PET Scanner. Mastectomy and axillary clearance was performed after chemotherapy. pCR was defined as no residual invasive tumor in breast and lymph nodes. TIL and lymphovascular invasion were evaluated pre and post NAC by 2 independent anatomopathologists dedicated to breast cancer. Delta TILS was defined as the difference between post chemotherapy and pre chemotherapy TIL. Results Thirty TNIBC pts were treated, 28 underwent surgery and 2 progressed during chemotherapy. Median follow-up was 39 months (8 – 86). 9/30 patients (30%) achieved pCR. Median disease free survival (DFS) was 41 months (2 – 86). Median TIL infiltration at diagnosis was 11% (0-60) and dropped to 1% after chemotherapy (0 – 80). Median delta TIL was - 9% (-50% – +40%). TIL increase after chemotherapy was associated with a decrease of DFS (14 months vs not reached ; p = 0,0009). LVI was present on surgical specimens in 12 cases (12/30, 43%; 12/21 non pCR pts 57 %). Presence of LVI after chemotherapy was significantly associated with a decrease of DFS in the whole population (21 months vs not reached ; p = 0.008) and no significantly among the patients without pCR (23 months vs not reached; p = 0.07). Conclusion To the best of our knowledge, it is the best pCR rate reported in TNIBC (2). We showed in this retrospective series of 30 TNIBC that dose dense dose intense chemotherapy is efficient in this population. Presence of lymphovascular invasion and TIL after neoadjuvant chemotherapy in TNIBC are strong prognostic factors associated with DFS. Systematic determination of post NAC TIL and LIV could be a surrogate to propose adjuvant treatment after NAC in TNIBC.

e12593 Background: Immune checkpoint inhibition with pembrolizumab plus neoadjuvant chemotherapy is now the standard-of-care in patients with high-risk triple-negative breast cancer (TNBC) based on the KEYNOTE-522 trial. The trial demonstrated that the addition of pembrolizumab improves pCR, but it is currently unclear which patients benefit most from the addition of immunotherapy (IO). We sought to identify which demographic and clinical characteristics were associated with response to neoadjuvant pembrolizumab plus chemotherapy. Methods: We performed a single institution, retrospective study of early-stage TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab between March 1st, 2020 and December 1st, 2022. We excluded patients who had not undergone definitive surgery. We collected demographic information, clinical and pathologic characteristics, and treatment data. Pathologic complete response (pCR) was defined by ypT0/Tis and ypN0. Multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by the City of Hope Institutional Review Board. Results: 67 patients were analyzed with a median age of 56 years and median BMI of 29. Self-reported racial groups included 25 Hispanic patients (37%), 23 non-Hispanic White (34%), 9 Asian (13%), 6 Black (9%), and 4 other/unknown (6%). 6 (9%) patients were BRCA1+ and 1 (1.5%) patient was BRCA2+. The majority of patients had invasive ductal carcinomas (91%), were clinical T2 stage (65.7%), and node negative (52.2%). The median number of cycles of neoadjuvant IO was 7 (IQR 4-8) and median months from start of IO to surgery was 6 (IQR 4.6-6.7). 42 (62.7%) patients had a pCR. Multivariate results showed that patients under 50 years at time of diagnosis (vs. age &gt; 50 years), those with grade 3 (vs. 2), and those receiving 7 or more cycles of pembrolizumab (vs. &lt; 7) had improved rates of pCR (ORs 5.7, 8.1, and 3.4, respectively, p &lt; 0.05). BMI, race, BRCA1/2 status, histopathology, clinical T and N stage, and timing of start and end of IO to surgery were not significantly associated with pCR. Conclusions: Younger TNBC patients with high tumor grade were more likely to respond to treatment with neoadjuvant pembrolizumab and chemotherapy. More cycles of treatment with pembrolizumab was also associated with response. Further research to identify which patients with TNBC benefit from the addition of pembrolizumab to chemotherapy is necessary to determine whether its additional toxicity and cost are warranted.

Objectives: Addition of carboplatin to standard neoadjuvant chemotherapy (NACT) for triple negative breast cancer (TNBC) remains controversial. There are several randomized trials showing that carboplatin increases the likelihood of achieving pathological complete response (pCR) in TNBC. Patients with TNBC who achieve pCR has been shown to have better disease-free and overall survival. The aim of this study was to asses the impact of adding carboplatin to standard NACT in TNBC in terms of pCR rates and toxicity. Methods:In this cross-sectional study, 252 consecutive patients with primary TNBC who were submitted to neoadjuvant chemotherapy between 2013 and 2018, in a single center, were selected. Patients with biopsy-confirmed TNBC, previously untreated, with clinical stages I-III were included (n=179). Clinical pathological features, pathological response, treatment protocol, and toxicities were analyzed and considered for statistical analysis. Eighty patients treated from 2013 to 2015 received doxorubicin plus cyclophosphamide once every 3 weeks (AC) for four cycles, followed by 12 weeks (wP) or every 3 weeks (P) paclitaxel(AC-T group). Ninety-nine patients, treated from 2015 to 2018 had four cycles of AC followed by wP plus weekly carboplatin (Cb) area under curve (AUC) 1.5-2.0 (AC-TCb group). Pathologic response was determined locally, and pCR was defined as the absence of residual invasive disease with or without ductal carcinoma in situ in the breast and axilla. Results: Data from 179 patients were included in the analysis (AC-T: n=80; AC-TCb: n=99). Patients in AC-TCb group had a median age of 51.7 years vs. 47.4 years in AC-T group, p=0.01. In AC-TCb group 61.6% of patients were postmenopausal vs 43.7% in AC-T group, p=0.03. The distribution of clinical stage in groups AC-TCb and AC-T were as follows: stage I 6.0% vs 0%; stage II 42.4% vs 43.7%; stage III 51.6% vs 56.3%, respectively (p=0.02). In AC-TCbgroup, 34 patients (35.0%) had pCR in comparison to 20 patients (25.0%) on AC-T group (p=0.22). Pathological stage distribution in groups AC-TCb and AC-T were: stage I 24.7% vs 33.7%; stage II 23.7% vs 26.3%; stage III 16.4% vs 15%, respectively (p=0.42). More than 85.0% of patients in AC-TCb group received at least 9 weeks of carboplatin and less than 20.0% required dose reduction due to toxicity.Conclusions: An improved pathological complete response for TNBC patients submitted to standard NACT plus carboplatin was observed. The results are in accordance with previous studies demonstrating that the addition of carboplatin to NACT improves pCR rate in TNBC with a favorable risk to benefit profile. Therefore carboplatin might be a potential component of NACT and should be considered in this context. Distribution of patients with TNBC submitted to NACT with AC-T and AC-TCb according clinical–pathological characteristicsClinical pathological characteristicsAC-T n= 80AC-TCb n=99pMenopausal 0.03yes3561 no4538 Clinical stage 0.02I06 II3542 III4551 Histologic type 0.25IDC8096 others03 Histologic grade 0.86101 22932 35164 Pathological stage 0.42O2034 I2724 II2123 III1216 pCR 0.22yes2034 no6063 Citation Format: Ramalho S, Natal RdA, Cardoso Filho C, Xavier MB, da Silva AER, Silva LR, Vasconcelos V, Reinert T, Coelho GP, Silva GRdP, dos Santos CC. Pathological complete response rates with the addition of carboplatin to standard neoadjuvant chemotherapy in a cohort of real–world patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-16.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for triple-negative breast cancer (TNBC). Systemic inflammation has been linked to cancer development and overall poor outcomes. Routine blood parameters have been investigated as potential inflammatory biomarkers in patients (pts) with various types of cancer, such as the derived NLR (neutrophils/(leucocytes-neutrophils) ratio (dNLR). A high dNLR has been associated with worse survival in several types of cancer. Specifically, it has been linked to lower pathologic complete response (pCR) rates after neoadjuvant chemotherapy (CTx). We investigated the association between systemic inflammation markers (dNLR, LIPI score and platelet-to-lymphocyte ratio [PLR]) and pCR in early TNBC pts treated with CTx + pembrolizumab (Pemb). Methods: Retrospective analysis of pts with early TNBC treated with Pemb + CTx from April 2022 to March 2023. dNLR was estimated from analytical values of peripheral blood collected before treatment (baseline). dNLR was calculated as the ratio of the absolute neutrophil number to the difference between absolute total leukocyte and absolute neutrophil counts. Univariate and multivariate logistic regression analyses were used to explore the association of dNLR with main clinical characteristics and dNLR capability (distributed as a continuous variable, using median cut-off) to predict pCR. Results: The study included 86 TNBC pts with a median age of 51 years (IQR: 42.2 – 56-7). Most pts had stage II disease (64%) and presented grade 3 tumours (n=66; 78.5%). HER2 low tumours represented 27% (n=23) of the cohort. Germline mutations were present in 20 pts (23%) with the following distribution: BRCA1 (n=14), BRCA 2 (n=5) and PALB2 (n=1). The median stromal tumor infiltrating lymphocytes (TILs) was 20% (IQR: 10-30%). The median Ki67 was 70% (IQR:50%-80%). All pts received Pemb. The majority of pts received carboplatin plus paclitaxel, followed by EC90 (n=77 (90%), while 10% (n=9) did not receive anthracyclines. Data concerning surgical outcomes was available in 80 pts. Pathological complete response rate was 61.2% (n=49). Pts achieving pCR presented significantly higher TILs (p&amp;lt; 0.01). Residual cancer burden (RCB) class (n=80) was distributed as follows: 0: 61% (n=49); I: 13% (n=10); II: 20% (n=16); III: 1% (n=1) and non-assigned: 5% (n=4). In pts with germline mutations (n=20), the pCR rate was 85% (n=17). Median dNLR at baseline was 1.30 (interquartile range (IQR): 0.99 – 1.86). High baseline dNLR levels considered a continuous variable was associated with a higher likelihood of achieving a pCR in univariate (OR: 2.59; 95% CI: 1.01–6.6; p-value = 0.046) but not in multivariate (OR: 2.33; 95%; CI: 0.85–6.33; p-value = 0.097) logistic regression analysis (adjusted for stage and histologic grade). High baseline dNLR, defined by the median cut-off, was associated with an increased likelihood of achieving pCR in both univariate (OR: 3.85; 95% CI: 1.47–10.1; p-value = 0.006) and multivariate (OR: 3.72; 95% CI: 1.28–10.8; p-value = 0.016) logistic regression analysis (adjusted for stage and histologic grade). Conclusion: In this real-life cohort of early TNBC pts treated with Pemb and CTx we found similar pCR rates (61.2%) to the ones reported in the KN522 trial. No association between PLR or LIPI score with pCR was evidenced. High baseline dNLR (assessed as a continuous variable or by the median cut-off) was associated with a higher likelihood of pCR in the univariate analysis. In the multivariate analysis, only high baseline dNLR defined by the median cut-off retained an association with pCR after stage and histologic grade adjustment. Despite several limitations, these exploratory data provide initial evidence of a potential association between dNLR values and independent prediction of pCR. Further research to assess the role of dNLR as a predictive marker for pCR in early TNBC pts treated with CTx + immunotherapy is needed. Citation Format: Martina Spotti, Elie Rassy, Alessandro Viansone, Fiona Pham, Layal Rached, Barbara Pistilli, Charles-Antoine Dutertre, Joana Mourato Ribeiro. Impact of systemic inflammation markers in response to neoadjuvant pembrolizumab and chemotherapy in triple-negative breast cancer - a retrospective analysis [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 PO5-13-08.

Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis. The KEYNOTE-522 study established the combination of pembrolizumab and neoadjuvant chemotherapy (NAC) as the recommended treatment for early TNBC. However, real-world evidence, especially in the Taiwanese population, is lacking. This multicenter retrospective study aimed to identify clinical characteristics and treatment variables associated with response to pembrolizumab plus NAC in early TNBC. Methods: We retrospectively reviewed the multicenter medical records of patients with early TNBC who were treated with pembrolizumab plus NAC between May 2018 and October 2023. The primary endpoint was pathologic complete response (pCR). Kaplan-Meier curves were used to evaluate event-free survival (EFS) and overall survival (OS). Statistical analyses included two-sample t-test, chi-square test, and univariate analysis with a significance threshold of 0.05. Results: Among the 72 patients in our study, the pCR rate was 51.4% (37/72). Median age at diagnosis was 50.5 years old (IQR 43.5–57.6), and mean body weight showed 58.1±9.4 kg. The rates of pCR for Stage II and Stage III patients were 56% and 41%, respectively. Kaplan-Meier curves for EFS according to pCR status after neoadjuvant treatment demonstrated a significant difference (log-rank test p = 0.003), although no significant difference was observed in overall survival (OS) with a median follow-up of 1.6 years (IQR 1.0–2.3). The probability of recurrence events was significantly associated with pCR (p = 0.001). In the pCR group, the recurrence rate was 0% (0/37), whereas in the non-pCR group, it was 25.7% (9/35). Additionally, optimizing neoadjuvant pembrolizumab dosage in a 100 mg setting of patients showed a remarkable difference in pCR rate, achieving 68% (p = 0.01) with a per-weight dose exceeding 1.8 mg/kg. Only achieve four NAC cycles of anthracyclines along with cyclophosphamide were shown to be substantially linked with achieving pCR, with a rate of 88% (p = 0.023) in univariate analysis. Conclusions: This real-world study provides valuable insights into the efficacy and tolerability of pembrolizumab in early TNBC. It highlights the importance of optimizing neoadjuvant pembrolizumab dosage to a per-weight dose exceeding 1.8 mg/kg in the 100 mg setting, which significantly improves the pCR rate and the completion of AC regimen cycles necessary for achieving pCR in Asian patients with early TNBC. Citation Format: Yu-Ting Lin, Liang-Chih Liu, Chin-Yao Lin, Chiann-Yi, Hsu, Chih-Chiang Hung, Ting-Yi, Liao. Effectiveness of Combined Neoadjuvant Pembrolizumab and Chemotherapy in Early Triple-Negative Breast Cancer: Real-World Evidence from Multiple Centers in Asia [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-08-13.

Background: Early-stage triple-negative breast cancer (TNBC) is associated with high risk of early recurrence and disease-specific mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). In TNBC, the combination of immunotherapy based on immune checkpoint inhibitors (anti-PD-1/PD-L1) combined with chemotherapy has been shown to be effective both in the advanced and early. In the early-stage setting, the addition of pembrolizumab to platinum-containing NACT significantly increased pathological complete response (pCR). Methods: We performed a retrospective observational cohort study of patients diagnosed with TNBC, stage II-III, who received NACT with chemotherapy based on paclitaxel and carboplatin (TC) followed by doxorubicin plus cyclophosphamide (AC) associated with pembrolizumab, treated from June 2022 to July 2023, at AC Camargo Cancer Center, São Paulo, Brazil. Objectives: To investigate the real-world pCR rate and safety profile of early-stage TNBC treated with neoadjuvant chemotherapy (weekly TC, ddAC/AC) associated with pembrolizumab and to describe the clinical-pathological characteristics of this population. Results: Eighty patients received neoadjuvant pembrolizumab plus chemotherapy. Around 50.6% of patients were premenopausal, with a median age of 47 years old at diagnosis. About 18% carried a germline mutation in the BRCA1 (50%) .Regarding the pathological characteristics of the tumor, 90.9% were invasive ductal carcinoma (IDC), 80% had histological grade (HG) III, and average Tumor Infiltrating Lymphocytes (TILs) was 18%. In 94.8% of cases, Ki67 was expressed in more 20% of tumor cells. The expression of HER2 was low in 14%, and 5% were ER-low. Regarding the clinical stage of the primary tumor, (64.9%)cT2, (18%) cT3, (10%) cT1c, and (2.5%) cT4. Regarding regional lymph node staging, 48%, 33.7%, 10.3%, and 6.4% were classified as cN0, cN1, cN2a, and cN, respectively. Clinical stage was IIA (42.8%), IIB (24.6%), IIIA (14.2%), IIIB ( 9%), and IIIC (5%). Regarding chemotherapy, 57.1% received dose dense AC, 54% percent had chemotherapy-related toxicity, 35.7% had neutropenic fever, 32.4% required hospitalization, and 31% used antibiotics. 31% received eight cycles of neoadjuvant pembrolizumab and 53.2% of patients completed all NACT, among these patients, 61% had complete .A cutoff date, about 61% of patients have undergone surgery, and 66.6% achieved a complete pathological response (ypT0ypN0). Patients that received eight cycles of neoadjuvant pembrolizumab had a higher chance of pathological complete response rate (61% vs. 45.2%) p=0.073. Immune-related toxicities (IRT) were observed in 16.8% patients, being the most common endocrinologic and cutaneous, being G3 or higher in 46%. About 15.5% used corticosteroids. Fifty percent had already started or completed adjuvant therapy, from which 66.6% received only adjuvant pembrolizumab, 28% had adjuvant pembrolizumab plus capecitabine, 1.2% received adjuvant capecitabine, and 1.2% had adjuvant olaparib. Eight percent of our patients have already completed nine cycles of adjuvant pembrolizumab, 12.7% did not receive adjuvant pembrolizumab due to prior toxicity. In our cohort, we observed greater intercurrences related to ddAC versus conventional AC 61.4% versus 52.4%, p=0.492, therefore, it did not impact whether or not the chemotherapy was completed. Conclusion: Our cohort is composed mostly of pre-menopausal with stage IIA tumors. Most patients received ddAC, Fifty-four percent had chemotherapy-related toxicity. We observed a high rate of pCR (61%) on our patients have already undergone surgery, 66.6% achieved a complete pathological response.Of those who received 8 cycles of neoadjuvant pembrolizumab had a higher chance of pathological complete response rate (61% vs. 45.2%) p=0.073 Citation Format: isadora sousa, Ana Carolina M. Comini, Italo BORGES, Flavia C. Balint, Livia alexandre Martins, Debora G. Sousa, Solange M. Sanches, Marcelle G. Cesca, Vladmir Cordeiro de Lima, Monique Tavares. Real-world efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy in Brazilian patients with early-stage triple-negative 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 PO3-03-06.

Simple SummaryInflammatory breast cancers (IBC) are very aggressive especially the triple negative ones, highlighting the importance of prognostic and predictive factors determination. The evaluation of tumor infiltrating lymphocytes (TIL) is advised in breast cancers but little is known in inflammatory breast cancers, especially the TIL variation, before and after neoadjuvant chemotherapy (NAC). We reported a series of 31 triple negative IBC treated with dose-dense dose-intense NAC and investigated post NAC TIL and TILs variation. We showed that pre-NAC immune infiltration was lower than in the non-inflammatory breast cancer and that TIL increase after NAC is associated with a decrease in EFS. These results suggest that patients whose tumors have TIL enrichment after NAC are at high risk of relapse and could be candidates for adjuvant treatment after NAC.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.

Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer.

A phase II, randomized, open-label study to evaluate low-dose pembrolizumab plus chemotherapy versus chemotherapy as neoadjuvant therapy for localized triple-negative breast cancer (TNBC) (PLANeT trial-Pembrolizumab Low dose in Addition to NACT in TNBC).