Difference In pCR Rates Research Articles

Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study.

LBA246 Background: FLOT was established as a perioperative therapy for GC/GEJC following the Phase 2/3 FLOT4 study conducted in Germany, with a pCR rate of 16% (Al-Batran et al, Lancet Oncol 2016). The global MATTERHORN study (NCT04592913) showed a statistically significant improvement in pCR with perioperative D + FLOT vs placebo (P) + FLOT in GC/GEJC at first interim analysis (Janjigian et al, ESMO Congress 2023). Subgroup analyses by region and country were completed to assess pCR rates with FLOT and benefit of D + FLOT across the global study population. Methods: Participants (pts) with resectable GC/GEJC were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT Q2W on Days 1 and 15 for 4 cycles (2 doses of D or P and 4 doses of FLOT pre- and post-operative), followed by D 1500 mg or P on Day 1 Q4W for 10 further cycles. Randomization was stratified by Asia vs non-Asia. pCR (Modified Ryan; central review) was assessed in prespecified (Asia) and post hoc regional subgroups, including 6 countries with the highest numbers of randomized pts. Results: Of 948 pts randomized globally, 180 pts (19%) were in Asia. pCR outcomes with FLOT in Asia were consistent with the global outcomes. pCR rates were improved with D + FLOT vs P + FLOT in all regions (Asia, Europe, North America and South America; Table), despite some imbalances in baseline characteristics and numerical differences in pCR rates by geographic location. The pCR rate with P + FLOT in the German subgroup (13%; 95% CI, 6.1–23.0) was similar to that with FLOT in the FLOT4 study. Improvement in pCR with D + FLOT vs P + FLOT was observed across subgroups by country. Similar trends across regional subgroups were observed for combined complete and near-complete response rate. Conclusions: In MATTERHORN, pCR was consistently improved with the addition of D to perioperative FLOT in GC/GEJC across geographic regions. The study is ongoing for the primary objective of event-free survival. Clinical trial information: NCT04592913 .[Table: see text]

Impact of body mass index on pathological response after neoadjuvant chemotherapy: results from the I-SPY 2 trial

PurposeIncreased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial.Methods978 patients enrolled in the I-SPY 2 trial 3/2010–11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression.ResultsThe median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI 0.68–1.63, P = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI 0.64–1.47, P = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (P = 0.09). Multivariate Cox regression showed there was no difference in EFS (P = 0.81) or OS (P = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years.ConclusionWe found no difference in pCR rates by BMI with actual body weight-based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

Clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy

ObjectiveThe present study aimed to evaluate the clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy (NAC). MethodsPatients with HER2 negative breast cancer receiving NAC from January 2017 to December 2020 were enrolled in this study. The clinicopathological characteristics, response to NAC, evolution of HER2 and prognostic value were retrospectively analyzed. Results410 patients were included. The proportion of HR positive disease in HER2-low cases was higher than in HER2-zero population (75.8 % vs. 65.8 %, P = 0.040). No statistical significant difference in pCR rate was observed between HER2-low and HER2-zero patients (33.8 % vs. 39.3 %, P = 0.290) when pCR was defined as ypTis/0ypN0. Exploratory analysis revealed that the pCR rate of HER2-low cases was significantly lower than HER2-zero patients in the entire population (19.8 % vs. 33.3 %, P = 0.004) and HR positive population (12.6 % vs. 29.9 %, P = 0.001) when pCR was defined as ypT0ypN0. The evolution rate of HER2 expression after NAC was 31.0 % in HER2-zero patients and 24.7 % in HER2-low patients. Compared with patients with HR positive disease, patients with TNBC had higher evolution rate of HER2 expression after NAC (37.7 % vs. 23.6 %). Significant association was observed between HER2 evolution with histology type and Ki-67 index in HER2-zero patients and with lymph node involvement, HR status and Ki-67 index in HER2-low patients. Prognostic impact of HER2 evolution was not observed. ConclusionsHR positive and HR negative HER2-low breast cancer exhibit different clinicopathological features, response to NAC and HER2 evolution after treatment.

Correlation between androgen receptor expression and pathological response rate in pre-operative HER2-positive breast cancer patients.

In this study, we aimed to explore the potential significance of AR expression in HER2-positive breast cancer patients who underwent neoadjuvant targeted therapy. Specifically, we investigated the correlation between AR expression levels and pathological complete response (pCR) rates. Our objective was to determine whether there were significant differences in pCR rates among HER2-positive breast cancer patients with different levels of AR expression. We conducted a retrospective analysis of 258 HER-2 positive breast cancer patients who underwent neoadjuvant dual-blocked standard therapy (following the NCCN Guideline 2021) at three breastcancer centers in southwest China. We analyzed the clinicopathological features and pCR rates of these patients. The cut-off value for AR expression level was calculated as the median value of 70%. We used the chi-square test to investigate the correlation between AR expression level and pCR rate, as well as other clinicopathological features. Out of the 258 patients analyzed, 154 (59.69%) achieved pCR. Based on the cut-off value of 70%, AR expression level was classified as low (AR ≤ 70%) or high (AR > 70%) expression. Our analysis revealed a significant correlation between AR expression level and pCR rate in HER2-positive breast cancer patients (P = 0.031). We also found a significant association between pCR rate and clinical stage (P = 0.033) and chemotherapy regimen (P = 0.034). Furthermore, subgroup analyses showed that the pCR rate was higher in patients with high AR expression levels compared to those with low AR expression levels. Additionally, we observed that patients with an ER/AR ratio of less than 1 had a higher pCR rate than those with an ER/AR ratio greater than 1 (P = 0.038). Our study findings suggest that HER2-positive breast cancer patients with high AR expression levels may achieve higher pCR rates when treated with neoadjuvant dual-blocked therapy. Overall, our results support the idea that AR expression levels have a significant correlation with pCR rates in HER2-positive breast cancer patients receiving this particular form of treatment.

Neoadjuvant immunotherapy in hepatocellular carcinoma: A systematic review and meta-analysis.

e16232 Background: The addition of immunotherapy in neoadjuvant hepatocellular carcinoma (HCC) has been studied recently in early phase clinical trials due to high rate of recurrence after surgery. We aim to systematically review the evidence of efficacy and safety of neoadjuvant immunotherapy treatment. Methods: We carried out a systematic search on MEDLINE, Cochrane, and ASCO meetings library. Screening was done to include clinical trials with HCC patients who underwent any combination of neoadjuvant immune checkpoint inhibitors (ICIs). Quality assessment was performed using methodological index for non-randomized studies (MINORS) tool. The primary efficacy outcomes evaluated included complete pathological response (pCR), major pathological response (MPR), 1 year recurrence free survival (RFS) and overall response rate (ORR). Treatment related adverse events (TRAE) were assessed as a safety outcome. Predefined subgroup analysis was performed based on studies including of tyrosine kinase inhibitors (TKIs) in regimen. Data was analyzed using R version 4.2.1. Results: 5 phase I/II clinical trials were included consisting of 96 patients. Trials administered neoadjuvant immunotherapy agents nivolumab (with TKI cabozantinib) (N = 1), camrelizumab (with TKI apatinib) (N = 1), cemiplimab (N = 1) and nivolumab plus ipilimumab (N = 2). 78(81.2%) of patients were males. 56(59.3%) of patients had viral etiology. 14(14.5%) patients had surgeries delayed or cancelled due to any cause per trial protocols. Meta-analysis of 96 patients from 5 trials showed a pooled pCR rate of 14.49% (95% CI: 6.82 to 23.93%) with low heterogeneity (I2 = 0%, p value 0.55). Pooling the MPR resulted in an estimate of 35.30% (95% CI: 18.80% to 53.57%) with significant heterogeneity (I2 = 58.8%, p value 0.04). Three trials with total 45 patients reported a 12-month RFS rate of 51.08% (95% CI: 40.59 to 70.67%) with significant heterogeneity (I2 = 84.2%, p value 0.002). The overall response rate was 13.7% (95% CI: 6.9 to 22.1%) (I2 =0%, p =0.8). Overall rate of TRAE of any grade was 73.8% (95% CI: 63.1 to 82.5%) (I2 = 83.4%, p &lt;0.001) among all trials and grade 3 adverse events was 21.21% (95% CI: 11.4 to 32.7%) (I2 = 33.8%, p = 0.159). 17(17.8%) patients had elevation in liver enzymes. On subgroup analyses, no difference in pathological outcomes, ORR and grade 3 adverse events was observed with addition of TKIs. Exploratory analysis showed no difference in pCR rates with single ICI vs combination with ipilimumab. Conclusions: The addition of ICIs in neoadjuvant settings appears to be a safe and feasible option. The addition of TKIs to neoadjuvant ICIs does not appear to affect pathological and safety outcomes. Further studies are needed to identify ICI based regimens to improve pCR rates and validate pathological outcomes in HCC after correlating with recurrence and survival.

Tumor-infiltrating lymphocytes (TILs) for prediction of response to platinum-based neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC).

e12620 Background: According to several previous trials the rate of pathological complete response (pCR) for patients with TNBC is increased when carboplatin is added to NACT. However, it is largely unknown which group of patients would truly benefit from platinum-based NACT and for whom chemotherapy could be de-escalated. Several clinical trials have evaluated the stromal TILs as an important prognostic and predictive biomarker in breast cancer. We assessed the pCR rates and the outcomes in patients with TNBC randomized to receive NACT ± Carboplatin regarding TILs status. Methods: The clinical data were obtained from 132 patients diagnosed with TNBC (ER&amp;PgR &lt; 10%) and treated with either anthracycline-taxane NACT (n = 68) or сarboplatin-based chemotherapy (n = 64) from 2017 to 2022 at N.N. Petrov National Medicine Research Center of Oncology. TILs were evaluated in 132 formalin-fixed paraffin-embedded tumor tissue samples stained with H&amp;E at baseline biopsies according to guidelines from the International TILs Working Group. Classification of TILs into low ( &lt; 10%), intermediate (≤10% to &lt; 40%) and high (≥ 40%) levels was performed. Data are presented using the methods of descriptive statistics. The differences between groups were assessed using the Сhi-square test. P-values below 0.05 were considered statistically significant. Results: The proportion of patients who achieved a pCR was higher in the carboplatin group 66% than in patients without carboplatin 35% (OR 3,5; 95% CI 1,71-7,17; p = 0,0006). There were 25 (18.9%), 77 (58.3%) and 30 (22.7%) patients with low ( &lt; 10%), intermediate (≤10% to &lt; 40%) and high (≥ 40%) levels of TILs, respectively. In total, the tumors with high TILs had a pCR rate of 63.3%, compared with 46.1% for low TILs (OR 2,0; 95% CI 0,87-4,67; p = 0,097). No significant statistical difference in pCR rates was shown between carboplatin-based and standard NACT groups with high TILs - 71% and 54%, respectively (OR 2,06; 95% CI 0,45-9,30; p = 0,346). When analyzing a group with low TILs infiltration, the pCR was more frequent in the platinum-based 64% compared to 31% in the standard NACT group (OR 3,9; 95% CI 1,72-9,00; p = 0,0011). Conclusions: These data may support the de-escalation of carboplatin-based NACT in patients diagnosed with TNBC with high TILs infiltration. Further investigations are warranted to explore the predictive value of TILs in platinum-based NACT. [Table: see text]

Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials.

To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT). A systematic review was performed according to the PRISMA guidelines. A Bayesian network meta-analysis was done using NetMetaXL and WinBUGS. This study was registered in PROSPERO on March 3, 2022 (No. CRD-42022307867). Outcomes of 2,719 patients from 10 randomized trials between 2010 and 2022 were selected. Of these 1,191 (44%) had conventional long-course CRT (50-54 Gy) and capecitabine, 506 (18%) had induction chemotherapy followed by CRT (50-54 Gy) and capecitabine (iTNT), 230 (9%) had long-course CRT (50-54 Gy) followed by consolidation chemotherapy (cTNT), and 792 (29%) undergone modified short-course radiotherapy (25 Gy) with subsequent chemotherapy (mTNT). Total pathologic complete response (pCR) was 20% in the iTNT group, 21% in the mTNT group, 22% in the cTNT group, and 12% in the CRT group. Statistically significant difference in pCR rates was detected when comparing iTNT with CRT (odds ratio [OR], 1.76; 95% credible interval [CrI], 1.06-2.8), mTNT with CRT (OR, 1.90; 95% CrI, 1.25-2.74), and cTNT with CRT groups (OR, 2.54; 95% CrI, 1.26-5.08). No differences were found in R0 resection rates. No significant difference was found in long-term outcomes. The early administration of systemic chemotherapy in the TNT regimen has improved short-term outcomes, though long-term results are underreported. Randomized trials with survival as the endpoint are necessary to evaluate the possible advantages of TNT modes.

Response to Treatment, Racial and Ethnic Disparity, and Survival in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy in the US

With the increasing delivery of neoadjuvant chemotherapy (NACT) for patients with breast cancer in the US, it is important to know whether there is differential response to NACT by race and ethnicity and the potential long-term outcomes. To examine whether there were any racial and ethnic differences in pathologic complete response (pCR) rate following NACT and, if so, whether they varied by molecular subtype and were associated with survival. A retrospective cohort study was conducted including patients with stage I to III breast cancer diagnosed between January 2010 and December 2017 who underwent surgery and received NACT; median follow-up was 5.8 years, and data analysis was conducted from August 2021 to January 2023. Data were obtained from the National Cancer Data Base, a nationwide, facility-based, oncology data set that captures approximately 70% of all newly diagnosed cases of breast cancer in the US. Pathologic complete response, defined as ypT0/Tis ypN0, was modeled using logistic regression. Racial and ethnic differences in survival were analyzed using a Weibull accelerated failure time model. Mediation analysis was conducted to measure whether racial and ethnic differences in the pCR rate affect survival. The study included 107 207 patients (106 587 [99.4%] women), with a mean (SD) age of 53.4 (12.1) years. A total of 5009 patients were Asian or Pacific Islander, 18 417 were non-Hispanic Black, 9724 were Hispanic, and 74 057 were non-Hispanic White. There were significant racial and ethnic differences in pCR rates, but the differences were subtype-specific. In hormone receptor-negative (HR-)/erb-b2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-positive (ERBB2+) subtype, Asian and Pacific Islander patients achieved the highest pCR rate (56.8%), followed by Hispanic (55.2%) and non-Hispanic White (52.3%) patients with the lowest pCR rate seen in Black patients (44.8%). In triple-negative breast cancer, Black patients had a lower pCR rate (27.3%) than other racial and ethnic groups (all >30%). In HR+/ERBB2- subtype, Black patients had a higher pCR rate (11.3%) than other racial/ethnic groups (all ≤10%). In mediation analysis, racial and ethnic differences in achieving pCR after NACT could explain approximately 20% to 53% of the subtype-specific survival differences across racial and ethnic groups. In this cohort study of patients with breast cancer receiving NACT, Black patients had a lower pCR rate for triple-negative and HR-/ERBB2+ breast cancer but a higher pCR rate for HR+/ERBB2- diseases, whereas Asian and Pacific Islander patients had a higher pCR rate for HR-/ERBB2+ diseases. Tumor grade and ERBB2 copy number could account for some of these within-subtype disparities, but further studies are warranted. Inability to achieve a pCR can mediate in part, but not entirely, the worse survival outcomes experienced by Black patients.

Abstract P1-01-06: Differences in breast tumor response to neoadjuvant chemotherapy by race- Is obesity the key?

Abstract Background: Breast cancer treatment includes neoadjuvant chemotherapy (NAC), offered to patients with locally advanced breast cancer and who may benefit from down-staging before conservation therapy. NAC allows for evaluation of treatment response with pathologic complete response (pCR) acting as a marker of survival. Black women receive NAC more frequently as they often present with more advanced stage tumors and the triple negative subtype. Furthermore, Black women without pCR following NAC are at greater risk of mortality. Obesity is a prognostic factor for breast cancer. Non-Hispanic Black women have the greatest prevalence of obesity in most states. Patients with higher Body Mass Index (BMI) have previously been shown to have lower rates of chemotherapy response. Data on racial and ethnic differences in pCR rates are limited and whether obesity is a confounding factor requires investigation. Methods: Retrospective review of patients diagnosed with non-metastatic breast cancer who completed NAC and had surgery at Ohio State University James Comprehensive Cancer Center between January 1, 2005, and December 31, 2019, were analyzed. Clinical stage was calculated based on tumor size and nodal status. Operative treatment received was recorded to determine pathologic stage and chemotherapy response. The study endpoint, pCR, was assessed after definitive surgery. BMI categories were based on World Health Organization classification and obese defined as 30kg/m2. For the data analysis, we included self-reported Black and White women, excluding patients classified as “Other” race. Preliminary analyses included the distribution of sample descriptive characteristics. Differences by race and demographic characteristics were compared using Pearson’s chi-square test for categorical variables and t-test or Wilcoxon rank-sum test for continuous variables. Univariate analysis and multivariable logistic regression for pCR by age, race, BMI, menopausal status, insurance status and employment status were performed. Results: A final sample of 882 met criteria (11.7% Black and 88.3% white women, 1% Hispanic ethnicity). Median age of diagnosis is 51, with median 147.4 months of follow-up. 64% of the sample had clinical stage 2 disease, 22% were triple negative, 62% Her-2 positive subtypes. For tumor characteristics 67% of Black women and 59% white women had high grade tumor. Black women also had more triple negative disease (30% vs. 21%), more advanced stage at presentation (27% vs. 21%). More white women were employed and had private insurance compared to Black women, who predominantly had public insurance. The median BMI was higher among Black women (31.5) than white women (28.6). 52% of white women vs. 47% Black had mastectomy over lumpectomy. 67% of white women had radiation vs. 61% of Black women. Overall, 33% of Black and white women had pCR, with 67% having no pCR. Race and BMI were not significant predictors of PCR rates on univariate or multivariable analysis. Age &amp;lt; 40 is the only variable associated with pCR (OR 1.645, [95 CI 1.117-2.420] p-value: 0.012). Conclusions: BMI was not a significant predictor of pCR in this limited retrospective review. However, further exploration with a larger sample evaluating differences in pCR by BMI can lead to a better understanding of the association between obesity and pCR. Though race was not significant in predicting pCR, there is also room for further research considering socioeconomic disparities and obesity rates by race. Table 1. Table 1. Predictors for pCR. Table 1. Multivariable logistic regression for pCR adjusted by age, race, BMI, menopause status, insurance status, employment status. Univariate analysis for predictors of pCR performed for race and BMI. Citation Format: Ruvarashe Rumano, Michael Grimm, Marilly Palettas, Julie Stephens, Nicole Williams, Sagar Sardesai, Dionisia Quiroga, Bhuvaneswari Ramaswamy, Electra Paskett, Bridget Oppong. Differences in breast tumor response to neoadjuvant chemotherapy by race- Is obesity the key? [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 P1-01-06.

Abstract P1-11-17: The real-world outcome of human epidermal growth factor type-2 positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab

Abstract Background Standard treatment in early HER2 positive BC involves the use of neoadjuvant chemotherapy (NACT) with Trastuzumab (T) plus Pertuzumab (P). Dual blockade increases pathological complete response (pCR) and improves disease free survival (DFS). However, Chilean public health system does not include P use in the NACT schedule, while private insurers only provide partial coverage. Here, we aim to compare pCR, Distant DFS (DDFS) and site of recurrence in HER2 positive BC patients treated in the neoadjuvant setting with the use of T with or without P, in the largest BC Chilean registry. Methods We conducted a retrospective population-cohort study involving females with stage I-III HER2 positive BC treated with NACT in a public and academic private centre between 2012 to 2021. CT regimens for comparison included anthracyclines, taxanes, T and P. pCR was defined as the absence of residual invasive disease in the breast and in the axillary lymph nodes (ypT0/is N0) at the completion of the NACT. DDFS was measured from the time of diagnosis to the event or lost to follow-up. We performed Cox regression analysis to identify factors associated with prognosis and a logistic regression to identify factors related to the first metastasis site. Results 372 patients with HER2 positive BC were included. Median age was 51 years (24 – 79), 57.5% were classified as Hormone Receptor positive (HR), and 4.5% were stage I, 48.2% stage II and 47.3% stage III. 65.8% were treated in a Public Hospital (PH) and 34.2% in an Academic Private Centre (AC). 85.2% received both anthracyclines and taxanes, 10.0% only taxanes and 4.8% only anthracyclines-based CT. 55 patients (14.8%) received both T and P, while 3.3% did not receive any HER2 directed therapy as NA treatment. Median T doses before surgery were 6 (1 – 12). pCR rate was 46.5% which varied according to HR expression: 61.0% in HR-positive BC vs. 36.2% in HR-negative disease (p=0.0001). pCR according to treatment were as follows: no-T no-P 22.2%, only-T 49.4%, both T-P 60.0% (p=0.02). We found no difference in pCR rate between anthracycline and non-anthracycline based CT (49.1% vs. 45.9%, p=0.72). With a median follow-up of 36 months, DDFS at 3 and 5 years differed regarding pathological response: 94.8% vs. 77.1% and 86.3% vs. 69.1% (p=0.0006), for pCR and non-pCR group, respectively. In a multivariate analysis, stage III vs. I-II (HR 2.5, p=0.005), non-pCR vs. pCR (HR 2.6, p=0.01) and not receiving NA anti-HER2 treatment (HR 2.6, p=0.01) were associated with higher risk of distant metastasis. Regarding recurrence, 7 out of 198 non-pCR tumors and 6 out of 174 pCR tumors presented brain metastasis (BM) as the first site of distant recurrence(p=0.96). In contrast, visceral metastasis (VM) as the first site of recurrence, were more frequent in non-pCR (21/198) than pCR patients (3/174, p=0.001). In a multivariate analysis, the only factor associated with BM was stage III (HR 5.8 vs stage I-II, p=0.02) and with VM was not achieving pCR (HR 6.3, p=0.02) and not using T nor P (HR 5.1, p=0.008). Conclusion The use of anti-HER2 treatment in a NA scheme is critical in HER2 positive disease. Although P is associated with increased pCR, we found no survival benefit with its use. Retrospective analysis, few events, post-surgical treatment might have influenced these results. Achieving pCR is associated with better prognosis by reducing distant recurrence but not BM. New strategies are needed to prevent the occurrence of this event. Citation Format: FRANCISCO ACEVEDO, Benjamin Walbaum, Lidia Medina, Tomas Merino, Catherine Bauerle, Mauricio Camus, Augusto Leon, Manuel Manzor, Paulina Veglia, Raul Martinez, Constanza Guerra, Marisel Navarro, Francisco Dominguez, CÉSAR SÁNCHEZ. The real-world outcome of human epidermal growth factor type-2 positive breast cancer patients receiving neoadjuvant therapy with or without pertuzumab [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 P1-11-17.

Abstract P6-01-02: Using MammaPrint on Core Needle Biopsy to Guide Neoadjuvant Chemotherapy for Invasive Breast Carcinoma

Abstract Introduction: MammaPrint, a 70-gene assay used to predict breast cancer recurrence, is typically obtained on the surgical specimen to guide the use of adjuvant chemotherapy. However, MammaPrint results obtained at the time of diagnosis on core biopsy specimen could allow consideration of neoadjuvant chemotherapy (NAC), particularly for tumors that may not traditionally be considered for NAC such as invasive lobular carcinoma (ILC). We hypothesized that MammaPrint scores correlate with pathologic complete response (pCR) and can predict NAC response independent of histology type. Methods: The National Cancer Database was used to identify patients with AJCC Stage I-III unilateral HR+/HER2- breast cancer with MammaPrint scores treated 2010-2018. Patients were stratified by histology: invasive ductal carcinoma (IDC) and ILC; and by MammaPrint score for 5-year breast cancer recurrence: Low Risk (1%) and High Risk (12%). Descriptive statistics identified clinical and treatment differences between groups. Logistic regression was used to identify factors associated with chemotherapy receipt and sequence. A subset analysis of patients receiving NAC compared pCR rates by MammaPrint score and histology type. Results: Of 10,999 patients, 9,351 (85%) were diagnosed with IDC and 1,648 (15%) with ILC. ILC were larger at presentation: 40% of ILC were cT2 or greater vs. 29% of IDC (p&amp;lt; 0.001). However, 90% of patients in both groups had cN0 disease. The majority of ILC were grade II (67% ILC vs. 52% IDC, p&amp;lt; 0.001). High Risk MammaPrint scores were significantly more common in IDC tumors: 44% IDC vs 25% ILC (p&amp;lt; 0.001). Mastectomy and axillary lymph node dissection (ALND) were performed more often for ILC than IDC (unilateral mastectomy 32% vs. 21%, bilateral mastectomy 17% vs. 12%, ALND 29% vs. 24%; all p&amp;lt; 0.001). Conversely, chemotherapy (38% vs. 30%, p&amp;lt; 0.001) and radiation (69% vs. 64%, p&amp;lt; 0.001) were more frequently used to treat IDC than ILC. In the subset analysis of patients who received NAC (n = 715), tumors with High Risk MammaPrint scores had more favorable in-breast and axillary responses than those with Low Risk scores for both ILC and IDC (Table 1). Furthermore, only tumors with High Risk Mammaprint scores achieved an overall pCR: 7% IDC and 5% ILC. There were no significant differences in pCR rates by histology type. On multivariable logistic regression, High Risk MammaPrint score was positively associated with the receipt of NAC (OR 4.3, p&amp;lt; 0.001) and adjuvant chemotherapy (OR 24.8, p&amp;lt; 0.001). NAC, adjuvant chemotherapy, and any chemotherapy were also strongly associated with node-positive disease and tumor size &amp;gt;2cm, but not IDC vs. ILC histology. Conclusions: Superior response to NAC was observed in tumors with High Risk MammaPrint score regardless of histology type, indicating a correlation between pCR rates and genomic assay results. Greater use of NAC guided by High Risk Mammaprint score obtained on core needle biopsy may allow patients with invasive breast cancer to undergo less extensive breast and axillary surgery. Further prospective studies using MammaPrint testing on core biopsy specimens could validate these findings in clinical practice. Table 1. Response to neoadjuvant chemotherapy by MammaPrint score for patients with Invasive breast carcinoma, NCDB 2010–2018 Citation Format: Lauren M. Drapalik, Rashi Singh, Ashley Simpson, Lisa Rock, Robert Shenk, Amanda L. Amin, Megan E. Miller. Using MammaPrint on Core Needle Biopsy to Guide Neoadjuvant Chemotherapy for Invasive Breast Carcinoma [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 P6-01-02.

Efficacy analysis of neoadjuvant chemotherapy with or without anthracyclines in female patients with HER2-positive breast cancer in China: a nationwide, multicenter, 10-year retrospective study (CSBrS-012).

In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial. Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group. The CSBrS-012 study (2010-2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC. A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran-Mantel-Haenszel test. A total of 2507 patients were enrolled: the anthracycline group (n = 1581, 63%) and the nonanthracycline group (n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65-2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13-3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33-0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM. In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.

Clinical, Pathological Complete Response, and Prognosis Characteristics of HER2-Low Breast Cancer in the Neoadjuvant Chemotherapy Setting: A Retrospective Analysis.

The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC]0) and HER2-low (defined as IHC1+, or IHC2+ and fluorescence in-situ hybridization-negative. Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p=0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p=0.023) and earlier clinical stage (p=0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p=0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p=0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p=0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p=0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

Anaemia and pathologic complete response rate according to carboplatin dose in HER2+ breast cancer treated with neoadjuvant TCHP.

Grade 3/4 anaemia, which is mainly induced by carboplatin, frequently occurs in patients treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). However, dose reduction of carboplatin may raise concerns about the oncological outcome. This study investigated the pathologic complete response (pCR) rate, occurrence of grade 3/4 anaemia, and transfusion rate according to carboplatin dose in patients treated with neoadjuvant TCHP. We retrospectively analysed 294 patients treated with neoadjuvant TCHP between April 2015 and December 2020. Case matching was performed using propensity score matching. Among patients treated with neoadjuvant TCHP, carboplatin area under the plasma concentration-time curve 6 (AUC6) was used in 234 patients (79.6%) and upfront carboplatin AUC5 was used in 60 patients (20.4%). No significant difference in pCR rate was found between the two groups (AUC6: 70.9%, AUC5: 80.0%). In both oestrogen receptor-positive (ER+) and ER- patients, no significant differences were observed between the AUC6 and AUC5 groups (ER+: 54.3% vs. 50.0%, ER-: 81.7% vs. 86.0%). The case-matched cohort showed consistent findings. The AUC5 group had lower frequencies of grade 3/4 anaemia (18.3% vs. 34.2%) and transfusion events (10.0% vs. 21.8%) than the AUC6 group. Compared with AUC5, carboplatin at AUC6 would associate with a 2.7-fold increased risk of grade 3 or 4 chemotherapy-induced anaemia. Carboplatin AUC5 has comparable cytotoxic effects to carboplatin AUC6 in patients with HER2+ breast cancer treated with six cycles of neoadjuvant TCHP, with fewer complications associated with clinically meaningful anaemia. AUC5 may be the optimal carboplatin dose to reduce TCHP-induced anaemia in patients with HER2+ breast cancer treated with TCHP.

Dose-dense neoadjuvant chemotherapy in triple-negative breast cancer: Real-world data from a developing country.

e12594 Background: Dose-dense adjuvant chemotherapy has been shown to be associated with improved long-term survival outcomes in triple-negative breast cancer (TNBC). However, there is a lacuna of data on the benefits of dose-dense neo-adjuvant chemotherapy (NACT) in TNBC particularly with respect to pathological complete response (pCR) rates and with the relapse or overall survival. To our knowledge no studies have been reported regarding the use or benefit of dose-dense NACT (ddNACT) over conventional NACT (cNACT) among Indian women with TNBC. Methods: This retrospective study included, 217 newly diagnosed cases of TNBC, treated with sequential anthracycline and taxane based NACT followed by definitive surgery. Study groups consisted of 137 patients who received 3-weekly conventional chemotherapy (cNACT group) and 80 patients with 2-weekly dose-dense NACT (ddNACT group) with granulocyte-colony-stimulating factor (GCSF) prophylaxis. Primary endpoint of the study was pathological complete response (pCR) rate and secondary endpoints were relapse-free survival (RFS), overall survival (OS) and grade-3/4 chemotoxicities. Fisher’s exact test was used to compare pCR rates. Kaplan-Meier and cox regression survival analysis were used to compare survival outcomes. Results: Median age (Interquartile range) in overall population, cNACT and ddNACT group were 43 (37-50), 44 (37-50) and 42 (36.5-48) years respectively. Baseline parameters were comparable between study groups, except that ddNACT group had higher proportion of premenopausal patients as compared to cNACT group (72.5% vs 55.5%). Majority of the patients presented at advanced stage, with stage-III being predominant, constituted by 97 (70.1%) and 55 (67.5%) patients in cNACT and ddNACT group respectively. No significant difference in pCR rate (32.8% vs 31.3%; p=0.808) was observed across the study groups. In multivariate analysis, dose-dense chemotherapy was no better than conventional chemotherapy for achieving pCR (Odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.45-1.63; p=0.639 and had no RFS advantage over conventional chemotherapy [Median RFS: Not reached in ddNACT vs 56.1 months in cNACT; Hazard Ratio: 0.83, 95% CI (0.48-1.44)]. OS was also comparable in both the groups with 3-year survival rate of 78.8% (95%CI: 60.9-89.2) in ddNACT group vs 84.3% (95% CI: 74.8-90.4) in cNACT group. Grade-3/4 toxicities were comparable in both groups. Conclusions: This observational study focusing on ddNACT among TNBC patients demonstrated similar pCR and toxicity rates with no significant survival benefits compared to cNACT regimen. Cost-benefits of frequent hospital visits for GCSF administration associated with dose dense therapy need further consideration before implementing such these regimens in lower-middle income countries.

Abstract P1-08-32: Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer: A meta-analysis

Abstract Background: Recent studies have explored the potential role of homologous recombination deficiency (HRD) as a biomarker and shown that the HRD status may be related to the pCR rate. However, does HRD specifically predict the efficacy of platinum chemotherapy, or only predict the benefit of the pCR, irrespective of the treatment regimen? Is there any difference in the efficacy of platinum supplementation between gBRCA1/2 carriers and HRD tumors without gBRCA mutations? Does the addition of platinum to neoadjuvant chemotherapy for patients without HRD bring no curative effects but only increase adverse reactions? We developed this meta-analysis and included all qualified relevant clinical trials to answer these research questions. Materials and methods: Eligible studies were systematically searched from inception to June 1, 2021, in the PubMed, Embase, Medline, Web of Science, and Cochrane databases, and in the abstracts of the European Society for Medical Oncology Congress and the American Society of Clinical Oncology Annual Meeting. The primary outcome was the pathological complete response (pCR, defined as ypT0/is ypN0) after neoadjuvant chemotherapy. Secondary outcomes included clinical response rates and grade 3 or higher adverse events. Classic forest plots were generated using standard techniques to present the meta-analysis results. Results: A total of 1404 patients were included in the present meta-analysis, of which the HRD status was measurable in 1142 (81.3%) patients, and 723 (51.5%) were confirmed to have HRD. Regardless of the HRD status, platinum-based neoadjuvant treatment was statistically associated with better pCR rates than platinum-free neoadjuvant regimens (51.3% vs. 37.6%, OR 1.93, 95% CI 1.13 - 3.30, p = 0.02). The pCR was higher in HRD patients receiving platinum than those without platinum exposure (56.7% vs. 39.4%, OR 1.95, 95% CI 1.17 - 3.23, p = 0.01), while no significant differences were identified between the platinum and control groups in non-HRD patients (36.5% vs. 20.5%, OR 1.82, 95% CI 0.61 - 5.40, p = 0.28). Irrespective of the treatment arm, the odds ratio of achieving the pCR was 3.35 times higher in patients with HRD than in non-HRD patients (51.6% vs. 27.4%, OR 3.35, 95% CI 1.93 - 5.81, p &amp;lt; 0.01). Moreover, among patients on platinum-based regimens, HRD patients had a significant pCR benefit compared to the non-HRD group (58.3% vs. 33.3%, OR 3.40, 95% CI 1.86 - 6.24, p &amp;lt; 0.01). For those without platinum exposure, the results revealed no difference in pCR rates, irrespective of the HRD status (34.3% vs. 20.5%, OR 1.89, 95% CI 0.81 - 4.43, p = 0.14). Among patients with HRD who received platinum-containing therapy, pooled results demonstrated no statistically significant difference between patients with BRCA mutations and those with BRCA wild-type (70.4% vs. 57.8%, OR 1.84, 95% CI 0.84 - 4.02, p = 0.12). With respect to clinical response rates, while more benefit was observed with the use of platinum in HRD and non-HRD patients, the difference was not statistically significant in the forest plot (85.1% vs. 76.1%, OR 1.97, 95% CI 0.91 - 4.27, p = 0.08). Additionally, our results revealed that grade 3 or higher adverse events were more frequently observed in patients on platinum-based regimens. Conclusion: Platinum-based neoadjuvant chemotherapy is associated with significantly higher pCR rates in early-stage triple-negative breast cancer patients with HRD, irrespective of BRCA status. Adding platinum to neoadjuvant treatment in the non-HRD population increases adverse reactions rather than improving the therapeutic effect. Citation Format: Yuanqi Chen, Liulu Zhang, Minyi Cheng, Xiaosheng Zhuang, Ci-Qiu Yang, Fei Ji, Hong-Fei Gao, Mei Yang, Teng Zhu, Jieqing Li, Kun Wang. Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-32.

Pathologic complete response to neoadjuvant anti-HER2 therapy is associated with HER2 immunohistochemistry score in HER2-positive early breast cancer.

To evaluate whether pathologic complete response (pCR) to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapy is dependent on the HER2 immunohistochemistry (IHC) score.A total of 181 HER2-positive early breast cancer patients who had received neoadjuvant anti-HER2 therapy were included in this study. Associations were examined between IHC score and tumor pCR status (commonly defined by ypT0+ypN0, ypT0/is+ypN0, or ypT0/is).In trastuzumab-based neoadjuvant-treated patients, ypT0+ypN0 was achieved in 46.0% of patients with HER2 IHC 3+ tumors but only 25.0% of patients with HER2 IHC 2+/fluorescence in situ hybridization (FISH)-positive tumors (P = .016). When pCR was defined as ypT0/is+ypN0 or ypT0/is, 54.7% and 61.3% of patients with HER2 IHC 3+ tumors had a pCR, whereas only 29.5% and 38.6% with HER2 IHC 2+/FISH-positive tumors achieved pCR (P = .004 and P = .008, respectively). The association between dual HER2 blockade and pCR was almost exclusively confined to HER2 IHC 3+ tumors (ypT0+ypN0: 61.9% vs 38.9%, P = .013; ypT0/is+ypN0: 71.4% vs 47.4%, P = .009; and ypT0/is: 81.0% vs 52.6%, P = .002) and was absent in HER2 IHC 2+/FISH-positive tumors. Multivariate logistic regression revealed that HER2 IHC 3+ tumors had a significantly higher probability of achieving ypT0+ypN0 (odds ratio [OR], 0.265; 95% confidence interval [CI], 0.109–0.645; P = .003), ypT0/is+ypN0 (OR, 0.221; 95% CI, 0.094–0.521; P = .001), and ypT0/is (OR, 0.254; 95% CI, 0.111–0.583; P = .001) than HER2 IHC 2+/FISH-positive tumors. A significantly better pCR rate was also found in patients with T1 tumors and patients with dual HER2 blockade.The pCR rate was highly correlated with the HER2 IHC score in neoadjuvant anti-HER2 treatment. The addition of pertuzumab to a neoadjuvant trastuzumab-based regimen improved pCR rates, but there was no significant difference in pCR rates in the IHC 2+/FISH-positive group. This suggests that HER2 IHC scores can predict the effectiveness of treatment.

Concurrent use of statins and neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and meta-analysis.

Statins are used primarily in patients with cardiovascular disease. More recently, they have demonstrated benefit in oncology patients. In vitro models have shown decreased rectal tumor cell viability in cells receiving chemoradiation and statin therapy. In vivo models have been less clear. This study aims to elucidate the impact of concurrent use of statins on the efficacy of neoadjuvant therapy for rectal cancer. Search of Medline, EMBASE, and CENTRAL was performed. Articles were included if they reported complete pathological response (pCR), long-term oncologic outcomes, or chemoradiotherapy-induced toxicity in patients with rectal cancer receiving concurrent statin and neoadjuvant therapy. A pairwise meta-analyses was performed using inverse variance random effects. From 1564 citations, six studies with 726 patients on statin therapy (24.5% female, age: 63.6years) and 1863 patients not on statin therapy (35.6% female, age: 60.9years) were included. There was no significant difference in pCR rate between patients on statin therapy and patients not on statin therapy (RR 1.23, 95%CI 0.98-1.54, p = 0.08). Similarly, no difference existed between groups in long-term oncologic outcomes (5-year overall survival: RR 1.03, 95%CI 0.86-1.24, p = 0.75; 5-year disease-free survival: RR 1.04, 95%CI 0.85-1.26, p = 0.73). Chemoradiotherapy-induced toxicities were similar between groups. The concurrent use of statin and neoadjuvant therapy did not significantly impact short- or long-term oncologic outcomes in patients with rectal cancer. Yet, despite pooling of data, this study remained inadequately powered. Larger, prospective studies are required to further elucidate the impact of statins on patients undergoing neoadjuvant therapy for rectal cancer.

123MO BARBICAN: A randomized, phase II study to determine the contribution of ipatasertib to neoadjuvant chemotherapy plus atezolizumab in women with triple-negative breast cancer

Pathological complete response (pCR) to neoadjuvant treatment in TNBC is strongly correlated with improved EFS and OS. Randomised trials have demonstrated increased pCR rates with the addition of checkpoint inhibitors to NACT in TNBC. Preclinical evidence suggests that AKT inhibition can enhance checkpoint inhibitor efficacy. The AKT inhibitor ipatasertib (IPAT) has shown promising activity in combination with paclitaxel as 1L therapy for metastatic TNBC. BARBICAN was designed to evaluate the clinical and biological effects of adding IPAT to NACT plus atezolizumab (atezo). International phase II, randomised trial in 146 patients (pts) with newly diagnosed, non-metastatic, high risk (node+ and/or tumour size ≥2 cm) TNBC. Patients were randomised (1:1) to receive one cycle of atezo (1200mg Q3W) ± IPAT (400mg D1-14), followed by 3 cycles of atezo (840mg Q2W) + weekly paclitaxel (80mg/m2) ± IPAT (400mg D1-21), followed by 4 cycles of atezo (840mg Q2W) + dose-dense doxorubicin (60mg/m2)/cyclophosphamide (600 mg/m2). Tumour biopsies were obtained at baseline, after each treatment phase and surgery. The primary clinical endpoint was pCR rate (ypT0/is ypN0). PD-L1 expression was assessed using the SP142 assay (1% cut-off). 144 pts received treatment, IPAT (n = 72) vs no ipatasertib (no-IPAT) (n = 72). There was no difference in pCR rates between treatment groups (chemo/atezo + IPAT, 49.3%, 95%CI, 36.8%-61.8%; chemo/atezo alone, 48.5%, 95%CI, 36.2%-61.0%). For IPAT vs no-IPAT, pCR was 66.7% vs 75.0% in the PD-L1-positive population (65 pts) and 32.4% vs 25.0% in the PD-L1-negative population (70 pts). pCR in node-positive pts was 55.6% (IPAT, 51.6%, no-IPAT 59.4%) compared to 43.1% (IPAT, 47.2%, no-IPAT 38.9%) in node-negative pts. Grade 3 or higher AE rates were 73.6% in the chemo/atezo + IPAT group and 40.3% in the chemo/atezo alone group, with rash, neutropenia, ALT increase, diarrhoea and mucosits being the most common. The majority of patients required IPAT dose modifications and the dose intensity was low. Addition of IPAT to neoadjuvant atezo plus chemotherapy did not improve pCR rates. IPAT dose intensity was low due to increased toxicity.

HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer

Knowledge on whether low expressions of HER2 have prognostic impact in early-stage breast cancer (BC) and on its response to current chemotherapy protocols can contribute to medical practice and development of new drugs for this subset of patients, changing treatment paradigms. This study aims to evaluate the impact of HER2-low status on response to neoadjuvant chemotherapy (NACT) and survival outcomes in early-stage HER2-negative BC. Records from all BC patients treated with NACT from January 2007 to December 2018 in a single cancer center were retrospectively reviewed. HER2-negative (immunohistochemistry [IHC] 0, + 1, or + 2 non-amplified by in situ hybridization [ISH]) patients were included. HER2-low was defined by IHC + 1 or + 2 ISH non-amplified and HER2-0 by IHC 0. The coprimary objectives were to compare pathological complete response (pCR) and relapse-free survival (RFS) between luminal/HER2-low versus luminal/HER2-0 populations and between triple negative (TNBC)/HER2-low versus TNBC/HER2-0. In total, 855 HER2-negative patients were identified. The median follow-up was 59months. 542 patients had luminal subtype (63.4%) and 313 had TNBC (36.6%). 285 (33.3%) were HER2-low. Among luminal patients, 145 had HER2 IHC + 1 (26.8%) and 91 had IHC + 2/ISH non-amplified (16.8%). In TNBC, 36 had HER2 IHC + 1 (11.5%) and 13 had IHC + 2/ISH non-amplified (4.2%). Most patients had locally advanced tumors, regardless of subtype or HER2-low status. For luminal disease, pCR was achieved in 13% of HER2-low tumors versus 9.5% of HER2-0 (p = 0.27). Similarly, there was no difference in pCR rates among TNBC: 51% versus 47% in HER2-low versus HER2-0, respectively (p = 0.64). HER2-low was also not prognostic for RFS, with 5-year RFS rates of 72.1% versus 71.7% (p = 0.47) for luminal HER2-low/HER2-0, respectively, and 75.6% versus 70.8% (p = 0.23) for TNBC HER2-low/HER2-0. Our data does not support HER2-low as a biologically distinct BC subtype, with no prognostic value on survival outcomes and no predictive effect for pCR after conventional NACT.