Predictive Value of Inflammatory Indexes as Biomarkers of Neoadjuvant Chemotherapy Response in Locally Advanced Breast Cancer

Introduction: HER2 gene amplificationis associated with shorter disease-free and overall survival in breast cancer.The prognostic value of the NLR, PLR, LMR or MLR has been also reported for many types of cancer. The aim of the present study was to assess the blood the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) as a prognostic factors in breast cancer patients (BC) according to HER2 overexpression. Material and Methods: A the retrospective analysis of 529 BC patients who were treated at COI (Gliwice, Poland) between January 2005 and June 2018 was performed. The prognostic value (OS) of the pre-treatment PLR, NLR and MLR was assessed by univariate and multivariate analysis. The cut-off values were determined using receiver operating characteristic curves. Based on the cut-off values determined, the NLR was considered as ‘elevated’ at >1.68, the MLR value was ‘elevated’ at >0.23 and the PLR was considered ‘elevated’ at>119.0. Result: The 5-year OS rates in HER2 positive and HER2 negative BC were 86.5 and 90.4%, respectively.The 5-year OS in the NLR >1.68 subgroup with HER2 (83.0 vs. 93.0%; P=0.579) and without HER2 overexpression (88.7 vs. 92.9%; P=0.159) were lower compared with a patients with NLR <1.68. Similarly, 5-year OS was lower in patients with a PLR of >119.0 with HER2 (85.9vs. 87.8%; P=0.782) and without HER2 overexpression (88.1 vs. 94.0%; P=0.060) compared with that in patients with a PLR of ≤119.0. The 5-year OS was similar in patients with a MLR of >0.23 with HER2 overexpression compared with that in patients with a MLR of ≤119.0 (86.1 vs. 86.7%; P=0.745). In group with a MLR of >0.23 without HER2 overexpression OS was lower compared with that in patients with a MLR of ≤0.23 (89.5 vs. 91.7%; P=0.185). Univariate Cox regression analyses of OS showed that in subgroup with HER2 overexpression factors such as tumor size (T3-4 vs. T1-2, HR=2.47; P=0.008), the presence of lymph node metastases (N+ vs.N0, HR=3.15; P=0.006) and estrogen receptor status (ER(+) vs. ER(-), HR=0.50; P=0.039) were statistically significant. Factors such as NLR, PLR and MLR were not statistically significant.Multivariate analysis revealed that in group breast cancer patients with HER2 overexpression negative prognostic factors were: tumor size and lymph node metastases. In contrary, positive prognostic factor was positive steroid receptor status (ER+).Univariate Cox regression analyses of OS showed that in subgroup without HER2 overexpression factors such as tumor size (T3-4 vs. T1-2, HR=3.89; P=0.0001), the presence of lymph node metastases (N+ vs.N0, HR=3.16; P=0.001), tumor grade (G3 vs. G1-2, HR=2.59; P=0.005), estrogen receptor status (ER(+) vs. ER(-), HR=0.43; P=0.012), progesterone receptor status (PR(+) vs. PR(-), HR=0.31; P=0.001), leukocytes >6.22 (HR=2.11; P=0.041), monocytes >0.52 (HR=2.24; P=0.018) and PLT>291 (HR=2.24; P=0.024) were statistically significant. Factors such as NLR (HR=1.66; P=0.166), PLR (HR=2.03; P=0.067) and MLR (HR=1.61; P=0.192) were not statistically significant. Multivariate analysis revealed that significant negative prognostic factors in without HER2 overexpression breast cancer patients were: tumor size, lymph node metastases and leukocyte number. In contrary, positive prognostic factor were positive steroid receptor status (PR+) and lymphocytes number. Conclusion: Elevated PLR, NLR and MLR worsens insignificantly prognosis in group of patients with tumors without HER2 overexpression. The presence of elevated MLR, PLR, NLR did not influence overall survival (prognosis) in group with HER2 overexpression. In both subgroups (HER2 positive and HER2 negative) common negative prognostic factors were tumor size and lymph node metastases. Citation Format: Joanna Huszno, Zofia Kolosza, Jolanta Mrochem Kwarciak, Aleksander Zajusz. Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio breast cancer patients according to HER2 overexpression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-67.

Response to neoadjuvant chemotherapy in breast cancer patients is of prognostic value in determining short- and mid-term outcomes. Inflammatory biomarkers, such as platelet-to-lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR), have been proposed as predictive factors of response to neoadjuvant chemotherapy. Currently, there are no studies in Colombian patients reporting the role of inflammatory biomarkers as response predictors in patients receiving neoadjuvant chemotherapy. Therefore, in this study we performed a cross-sectional study and analyzed the association between inflammatory biomarkers and pCR (pathological complete response) in patients diagnosed with breast cancer–of different molecular subtypes- and treated with neoadjuvant chemotherapy. A total of 288 patients were included in the study, with a median age of 51 years old. Disease was locally advanced in 83% of the participants, and 77.7% had compromised lymph nodes. In our cohort, the most frequent tumor molecular subtype was luminal B/Her2- (27.8%) followed by triple negative [TN] (21.5%), luminal B/Her2+ (19.8%), Her2-enriched (16%) and luminal A (13.5%). PLR was not associated with age, menopausal status, baseline tumor size, histologic grade, axillary lymph node involvement, disease stage, estrogen receptor status, or Ki67; however, complete pathological response was significantly higher in the low PLR group (PLR<150) compared with the high PLR group (35.1% Vs. 22.2%, p = 0.03). In addition, Her2-enriched tumors achieved the highest pCR rates (65%), followed by TN (34%) tumors. Our results suggest that breast cancer patients with low platelet-to-lymphocyte ratio (PLR <150), treated with neoadjuvant chemotherapy achieve higher complete pathological response, independently of primary tumor molecular subtype.

Introduction: TNBC is overrepresented in Black women, and Black patients (pts) with TNBC have worse clinical outcomes compared to non-Black pts. Neoadjuvant chemotherapy (NACT) +/- immunotherapy is current standard of care for early-stage TNBC. Immune response parameters including sTILs are important predictors of response to NACT and long-term outcomes in TNBC. Circulating blood cell counts may be indicators of the systemic immune environment and thus play a role in response to NACT. Racial differences in sTILs and peripheral white blood cell components and their combined impact on outcomes are not well studied in TNBC. Methods: 469 pts with stage I-III TNBC enrolled in a prospective registry between 2011-2023 who received NACT (n=321) or NACT + pembrolizumab (P) (n=148) were included in analysis. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and absolute monocyte count (AMC) were extracted from complete blood count (CBC) obtained prior to starting NACT. sTILs were centrally quantified as previously described. Impact of sTILs and CBC components (ANC, ALC, AMC, NLR (neutrophil to lymphocyte ratio), LMR (lymphocyte to monocyte ratio), and platelet to lymphocyte ratio (PLR)) on pathologic complete response (pCR) and recurrence free survival (RFS) was evaluated. Results: Among 469 pts, 33% had node positive disease; 81% were White, 14% Black, and 2% Asian. Pts who received NACT+P were more likely to have higher T stage (p=0.005) and TNM stage (p=0.004) and shorter follow up compared to those who received NACT alone. Black pts had lower ANC (median 3.6 vs 4.6 k/uL, p&amp;lt;0.001) and NLR (median 1.6 vs 2.5, p&amp;lt;0.001), and higher ALC (median 2.2 vs 1.8 k/uL, p=0.003) and LMR (median 4.4 vs 3.8, p&amp;lt;0.001) compared to non-Black pts. AMC was numerically lower in Black pts, and PLR was similar between Black and non-Black pts. sTILs were available for 55% (n=257) of pts; Black pts had higher sTILs compared to non-Black pts (median 40% vs 10%, p=0.019). There was no association of sTILs with ANC, ALC, NLR, LMR, or PLR. There was a weak inverse association of sTILs with AMC (p=0.013). pCR rate was similar in Black and non-Black pts (52% vs 55%). sTILs were associated with pCR both as a continuous variable (odds ratio, OR 1.12 for every 10% increase, p=0.009) and at 30% cut point. None of the CBC components were associated with pCR. Increasing AMC and LMR were associated with lower RFS (AMC: hazard ratio, HR 1.11 for every 0.4 k/uL increase, p=0.019, LMR: HR 1.28 for every 1.0 increase, p=0.002). None of the other CBC components, sTILs, nor race were associated with RFS. On multivariable analysis that included T stage and nodal status, AMC and LMR were each independently associated with RFS (AMC: HR 1.10, p=0.054; LMR: HR 1.07, p=0.016). Conclusion: Among all circulating blood cell components, only the ones that included monocytes (AMC and LMR) independently impacted RFS, with higher monocytes being associated with worse outcomes in TNBC. Positive correlation between circulating monocytes and tumor-associated macrophages (TAMs) has been previously reported. It is also possible that the chemokine axis may recruit inflammatory monocytes into tumor sites, which may in turn differentiate into TAMs. We noted weak inverse association of AMC with sTILs, which also suggests some relationship between monocytes and the tumor immune microenvironment (TIM). Compared to non-Black pts, Black pts were more likely to have immune-enriched tumors (higher sTILs) but had more unfavorable peripheral white blood cell immune environment (higher LMR). These findings may partly explain why high sTILs do not translate into improved pCR rate and RFS in Black pts. Further investigation is warranted into the interaction between TIM, circulating monocytes, and race and how these interactions impact response to therapy. Citation Format: Priyanka Sharma, Rachel Yoder, Joshua M. Staley, India Fernandez, Adam Heinrich, Spencer Thompson, AnneMarie Ball, Trinity Kemp, Andrew K. Godwin, Rashna Madan, Qamar J. Khan, Robert Salgado, Shane R. Stecklein. Impact of racial differences in circulating blood components and stromal tumor-infiltrating lymphocytes (sTILs) on outcomes in triple negative breast cancer (TNBC) [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 PS1-02.

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.

In this study, our aim was to explore the correlation between blood inflammatory markers (BIMs), including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR), and the efficacy of neoadjuvant chemotherapy (NACT) in BC patients. Besides, the relationship between tumor infiltrating inflammatory cells (TIIs) and BIMs has also been preliminarily studied. A total of 315 BC patients between January 2018 and September 2022 were analyzed. Receiver operating characteristic curve was used to determine the cut-off value of each BIM. Logistic regression analysis were used to evaluated the predictive power of BIMs for pathological complete response (pCR). TIIs were assessed by immunohistochemistry, and their relationships with BIMs also were analyzed. The results showed that NLR, MLR, PLR in the pCR group were significantly lower than those in the non-pCR group after NACT (p ≤ 0.05). PLR had the largest area under the curve (AUC) (0.73) compared to NLR (0.57) and MLR (0.67) (p &lt; 0.01). Univariate analysis showed ER, PR, HER2, NLR, MLR, PLR were significantly associated with pCR, but multivariate analysis found only HER2 and PLR were independently predictors for pCR (p &lt; 0.01). PLR was positively correlated with the expression of P-selectin in tumor tissue (r: 0.26, p &lt; 0.01). Survival analysis showed that NLR, MLR, PLR had no significant correlation with disease prognosis. In conclusion, PLR after NACT could serve as a predictor for pCR, and it correlated with the imbalance of the tumor-infiltrating platelet to lymphocyte ratio, which might cause drug resistance.

The immune system plays a fundamental role in the response to neoadjuvant chemotherapy (NAC) of locally advanced breast cancer (LABC) patients. Patients with pathological complete response (pCR) after NAC have a higher survival rate. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are peripheral blood indicators of inflammatory response. This investigates the correlation between NLR, PLR, LMR, and other clinicopathological features of breast cancer patients before receiving NAC and pCR.Data of LABC patients who underwent NAC between 2009 and 2018 were retrospectively reviewed. Each patient's peripheral complete blood count was recorded before starting NAC. The cut-off values for neutrophils, lymphocytes, monocytes, and platelets in the peripheral blood and NLR, PLR, and LMR were determined by receiver operating characteristic curve analyses.The records of 131 patients were analyzed and divided into two groups, pCR (+ve) and pCR (−ve), and their clinicopathological features and laboratory findings were compared. pCR was achieved in 23.6% of patients. The cut-off values of neutrophils, lymphocytes, monocytes, and platelets at the time of diagnosis and NLR, PLR, and LMR were, respectively, 4150 μL, 2000 μL, 635 μL, 271 × 103 μL, 1.95, 119, and 3.35. The pCR rate was higher in patients with low neutrophil count, low NLR, and high lymphocyte count (P = .002, <.001, and .040, respectively).As per the findings of multivariate logistic regression analysis, the independent predictive factors of pCR were clinical tumor size T1 and T2, grade 3, ER negativity, and low NLR (P = .015, .001, .020, .022, and .001, respectively).While NLR was found to be an independent predictive factor of pCR in LABC patients receiving NAC, a similar result was not observed for PLR and LMR. NLR can be a useful biomarker for predicting the response of patients receiving NAC.

Purpose: To evaluate the prognostic potential of inflammatory response biomarkers neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in predicting the outcome of rectal cancer patients undergoing neoadjuvant chemoradiation prior to surgery. Methods: Retrospective review of T3/T4, or N+ rectal cancer treated with neoadjuvant chemoradiation 50.4 Gy concurrently with either 5 FU (1 g/m2/d) or Capecitabine 825 mg/m2 twice daily. Four additional cycles of 5-FU chemotherapy (500 mg/m2/d, i.v. bolus) or capecitabine (2500 mg/m2 days 1-14, repeated day 22), were applied post-operatively. Pre-treatment NLR, dNLR, PLR and LMR calculated from peripheral blood cell were compared with clinicopathological parameters. The prognostic value of baseline NLR, dNLR, PLR and LMR for disease free survival (DFS) and overall survival (OS) were assessed using Log rank and Cox regression. Results: The final analysis included 80 patients, the receiver operating curve (ROC) calculated cut off values of baseline NLR, dNLR, LMR and PLR in predicting outcome were 3, 2.1, 4.9 and 169 respectively. Elevated NLR, dNLR, PLR, LMR, age of patients (≥50 years), depth of invasion ≥T3, lymph node N1-N2, stage III, grade 3 tumors, and partial response to preoperative chemoradiation were significantly associated with decreased OS, and DFS. Multivariate analysis revealed that elevated NLR and dNLR were independent Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation factors for worse OS and DFS hazard ratio (HR) 2.34 (95% CI=3.41-7.24), 4.53 (95% CI, 2.61-8.32) and DSF with (HR) 1.84 (95% CI=2.27-5.36), 4.23 (95% CI=3.49-9.52) respectively. Conclusion: The baseline NLR, dNLR, LMR and PLR showed a significant association with different clinicopathological prognostic factors in rectal cancer patients receiving preoperative chemoradiation. Additionally, NLR, dNLR may be considered as potential independent prognostic indicators of clinical outcomes.

Baseline Lymphocyte Counts Do Not Predict Oncologic Outcomes and Survival in Patients Receiving Short Course Total Neoadjuvant Therapy for Rectal Cancer

544 Background: Neoadjuvant chemotherapy (NCT) using anthracyclines and taxanes is a standard treatment for locally advanced breast cancer and pathologic complete response (pCR) is a major prognostic factor for survival. Gene polymorphisms have been identified as modulators of chemotherapy response. Our study investigated constitutional variants of genes associated with a change in the response to neoadjuvant chemotherapy using taxanes and/or anthracyclines in patients with breast adenocarcinoma. Methods: From November 2007 to January 2012, 118 women with breast adenocarcinoma histologically proven, with no Her2 surexpression, receiving or having received a neoadjuvant chemotherapy with taxanes and/or anthracyclines were included in the study. NCT associated 3 FEC100 then 3 Docetaxel every 21 days. Genotyping of 46 SNPs was performed on germline DNA using real time PCR. pCR was correlated to clinical characteristics and genotypes using univariate logistic regression. Results: 21.2% had a pCR according to Sataloff classification. pCR is increased in SBRIII (p=0.009), estrogen receptor negative (p=0.005) and triple negative (p=0.006) tumors. 7 SNP are significantly associated with pCR in ER+ breast tumors (pCR=13.5%). Among these SNP, pCR is increased for patients carrying almost one G allele for SLCO1B3-rs11045585 (pCR=28.6%; p=0.032), for homozygotes GG for SHTM1-rs1979277 (pCR=24.3%, p=0.006) and for homozygotes CC for CYP1B1-rs1056836 (pCR=25.7%; p=0.003). Moreover, 4 SNPs are significantly associated with pCR in ER- breast tumors: ERCC1-rs11615 (carriers of almost one C allele: pCR=50%; p=0.030), CD24-rs52812045 (Homozygotes CC pCR=56.3%, p=0.033), CYP2B6-rs2279343(carriers of one or two G allele: pCR=52.6%; p=0.046) and GSTP1-rs1695 (carriers of one or two G allele: pCR=48%; p=0.050). Conclusions: Besides ER status, polymorphisms could be useful markers to predict response to anthracyclines/taxanes NCT in breast cancer. Furthermore, this work is the first describing ERCC1-rs11615, SLCO1B3-rs11045585 and SHTM1-rs1979277 as new potential genetic markers for NCT in breast cancer. (The first 3 authors contributed equally to this work.)

In cancer patients, prognostic markers are needed to improve the management and clinical course of both the cancer itself and surgery therefor. Elevated systemic inflammatory markers are associated with morbidity and mortality in most cancer types. In this study, we aimed to determine the prognostic value of inflammatory markers such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) in patients undergoing cytoreductive surgery for ovarian cancer. The data of 188 patients who underwent surgery for ovarian cancer between December 2022 and December 2023 were retrospectively analyzed. Receiver operating characteristic (ROC) curves were constructed to evaluate the correlation between complications and the inflammatory prognostic factors NLR, PLR, and LMR. Optimal cutoff values were determined as the points where the Youden index (sensitivity + specificity - 1) was maximal. Patients were compared according to the presence of complications. As a result of the ROC curve analysis, patients were divided as high and low NLR and PLR groups. The difference of preoperative and postoperative inflammatory prognostic factors was compared according to the presence of complications. In this study in which a total of 90 patients were evaluated, the cutoff value for NLR was 2.04 (areas under the ROC curve: 0.655; P < .05) and the cutoff value for PLR was 145.3 (areas under the ROC curve: 0.740; P < .05) according to the presence of complications. In the group with complications, lymphopenia and thrombocytosis were more common preoperatively, while patients were more anemic postoperatively (P < .05). Patients in the high NLR group were younger and received less neoadjuvant chemotherapy. In the high PLR group, the number of patients receiving neoadjuvant chemotherapy was lower, and although the patients were more anemic and lymphopenic, higher rates of neutrophilia and thrombocytosis were observed. The analysis of preoperative and postoperative NLR, PLR, and LMR differences revealed an increase in NLR and PLR values and a decrease in LMR values (P < .05). The preoperative systemic inflammatory biomarkers NLR and PLR may be considered as prognostic predictors of poor postoperative outcomes. Therefore, consideration of these biomarkers may have an important role in clinical course management.

e11508 Background: Neoadjuvant chemotherapy (NACT) has been the standard for patients with inflammatory (IBC) and locally advanced breast cancer (LABC) and increases breast conservation rates in patients with operable tumor. Pathologic complete response (pCR) after NACT has been accepted as a marker for improved long-term outcome and predictors of pCR have been reported in many trials. However, predictors of progression or stable disease have been limitedly reported. We aimed to identify predictors of no response during NACT to identify patients who might benefit from an alternative approach. Methods: The medical records of patients with breast cancer who received NACT were reviewed retrospectively at a single center. Between March 2000 and January 2010, 316 patients were enrolled with stage I to III breast cancer. Statistical analyses were performed to compare patients with any response (RG) with patients with progression or stable disease (NRG). Results: Out of 316 patients, 263 patients (83.2%) had some response, 36 (11.4%) had SD, and 17 (5.4%) had PD during NACT. Factors predictive of NRG included nodal (N) status (p=.007) and clinical stage (p=.004), IBC cancer type (p=.02), negative estrogen receptor (ER) status, and negative HER2 status (p=0.04). Pre-NACT N stage, ER status, cancer type, and treatment with trastuzumab were independent predictors of NRG in multivariate analysis. NRG was a negative predictor of disease-free survival (p=.002) and overall survival (p=.026) in multivariate analysis. Conclusions: Factors predicting NRG include advanced nodal stage, ER negativity, IBC and NACT without trastuzumab in HER2-positve tumors. Because these variables are associated with poor prognosis, novel targeted therapies and molecular predictors are needed to improve outcome

IS10-6 - Predictive Factors of no Response During Neoadjuvant Chemotherapy in Breast Cancer

Background Obesity seems to be associated with a poorer response to adjuvant chemotherapy in breast cancer (BC); however, associations in the neoadjuvant chemotherapy (NACT) setting and according to menopausal status are less studied. This study aims to investigate the association between pretreatment body mass index (BMI) and pathological complete response (pCR) following NACT in BC according to menopausal and estrogen receptor (ER) status. Material and Methods The study cohort consisted of 491 patients receiving NACT in 2005–2019. Based on pre-NACT patient and tumor characteristics, the association between BMI and achieving pCR was analyzed using logistic regression models (crude and adjusted models (age, tumor size, and node status)) with stratification by menopausal and ER status. Results In the overall cohort, being overweight (BMI ≥25) compared by being normal-weight (BMI <25), increased the odds of accomplishing pCR by 15%. However, based on the 95% confidence interval (CI) the data were compatible with associations within the range of a decrease of 30% to an increase of 89%. Stratification according to menopausal status also showed no strong association: the odds ratio (OR) of accomplishing pCR in overweight premenopausal patients compared with normal-weight premenopausal patients was 1.76 (95% CI 0.88–3.55), whereas for postmenopausal patients the corresponding OR was 0.71 (95% CI 0.35–1.46). Discussion In a NACT BC cohort of 491 patients, we found no evidence of high BMI as a predictive factor of accomplishing pCR, neither in the whole cohort nor stratified by menopausal status. Given the limited precision in our results, larger studies are needed before considering BMI in clinical decision-making regarding NACT or not.

Background: Human epidermal growth factor receptor 2 (HER2) status can undergo alteration following neoadjuvant chemotherapy (NAC) in breast cancer. This study aimed to investigate the alteration of HER2 status after NAC in breast cancer and its impact on clinical outcomes of patients, focusing on HER2-low status. Methods: We retrospectively reviewed 1,063 breast cancer patients who received NAC followed by surgery between 2013 and 2020. Using paired samples of 670 patients with residual disease, HER2 discordance rate between pre- and post-NAC samples, the relationships between HER2 discordance and clinicopathological characteristics, and clinical outcomes of the patients were analyzed. Results: As a whole, HER2-low status before NAC was associated with a lower pathological complete response rate and higher Residual Cancer Burden (RCB) class, compared with HER2-zero and HER2-positive status. However, in subgroup analysis by hormone receptor (HR) status, no statistical differences were found in chemo-responsiveness between HER2-low and HER2-zero breast cancers. Following NAC, the overall HER2 discordance rate was 21.2% (κ = 0.676). The most common type of alteration was zero-to-low (10.8%) conversion, followed by low-to-positive (3.4%) conversion. HER2 discordance was significantly associated with lower HER2 levels and HR positivity before NAC, as well as lymphovascular invasion, higher ypT stage, lymph node metastasis, and higher RCB class in residual disease after NAC. In further analyses, HER2-zero-to-low conversion showed an association with HR positivity and low histologic grade. In multivariate logistic regression analyses, HR positivity and higher RCB class were identified as independent predictive factors for HER2 discordance. In survival analyses, HER2 discordance revealed a worse prognostic impact on disease-free survival of the patients, particularly within HR-positive subgroup, which remained statistically significant on multivariate Cox regression analysis. However, no survival differences were found between patients with HER2-zero-concordant and those with zero-to-low conversion. Conclusion: Given the prognostic implications of HER2 discordance, which primarily involves zero-to-low conversion, and the therapeutic benefits of newly developed antibody-drug conjugates in HER2-low breast cancer, HER2 status should be re-evaluated in surgical resection specimens following NAC, especially in cases showing HR positivity and high RCB class. Citation Format: Hyun-Jung Sung, Hyun Jung Kwon, Hee-Chul Shin, Eun-Kyu Kim, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park. Alteration of HER2 status following neoadjuvant chemotherapy in breast cancer: a clinicopathological analysis focusing on HER2-low status [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 P1-07-02.

It is essential in the management of ovarian cancers to identify the patients who will benefit from primary complete cytoreductive surgery and those who will rather benefit from neoadjuvant chemotherapy. To evaluate the predictive value of preoperative inflammatory markers, i.e. platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), red cell distribution width (RDW), and serum CA125 level for surgical outcome in epithelial ovarian cancer. A retrospective study was carried out in Sanglah Hospital, Denpasar, Bali. A total of 54 patients with epithelial ovarian cancer who underwent primary exploratory laparotomy from January 2018 to November 2019 was recruited. Data about clinical characteristics, preoperative inflammatory markers, serum CA125 level, and surgical outcome (optimal vs. suboptimal) was collected from the medical records. Predictive value of the markers were evaluated using ROC curve to determine their accuracy (area under the curve, sensitivity, specificity, positive and negative predictive value). Mean age, parity, and tumor size did not differ between the study groups (p> 0.05). The group with suboptimal outcome had significantly higher PLR, NLR, MLR, and RDW value (p< 0.05). Using the ROC curve, a cut off value was determined for each predictor, i.e. PLR: 196.50, NLR: 3.34, MLR: 0.24, RDW: 13.19, CA125: 300.85. AUC for each predictor were as follows: PLR 0.718 (95% CI: 0.578-0.859), NLR 0.676 (95% CI: 0.529-0.823), MLR 0.700 (95% CI: 0.560-0.839), RDW 0.712 (95% CI: 0.572-0.852), CA125 0.593 (95% CI: 0.436-0.750). Sensitivity, specificity, and accuracy for predicting suboptimal outcome were as follows: PLR (74.2%, 69.6%, 72.2%), NLR (64.5%, 60.9%, 62.9%), MLR (74.2%, 59.1%, 66.7%), RDW (74.2%, 60.9%, 68.5%), CA125 (54.8%, 60.9%, 57.4%). We have some limitations such as small numbers of sample, we generalized whole kinds of ovarian cancer, and this study does not describe follow-up features. Preoperative serum inflammatory markers (PLR, MLR, and RDW) may serve as useful markers to predict the surgical outcome with fair accuracy in patients with epithelial ovarian cancer.