Anthracycline-based Neoadjuvant Chemotherapy Research Articles

Differential Effects of Anthracycline-based Neoadjuvant Chemotherapy on Stromal and Intratumoral FOXP3+ Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer of No Special Type

BACKGROUND: Neoadjuvant chemotherapy (NAC) plays a crucial role in the management of invasive breast cancer with no special type (IBC-NST), with the immune system's response to cancer heavily relying on the dynamics between tumor-infiltrating lymphocytes (TILs) and cancer cells. In this study, the differential effects of anthracycline-based NAC on stromal and intratumoral foxhead box P3 (FOXP3+) TILs expressions were specifically examined.METHODS: In this cross-sectional study, 32 IBC-NST samples were evaluated for pre- and post-NAC FOXP3+ TIL expression as well as the changes of FOXP3+ TIL expression. Comprehensive data collection regarding subjects' age, tumor size, grade, lymphovascular invasion, regional lymph node metastasis, and receptor status were conducted. Immunohistochemistry was utilized to quantify FOXP3+ TILs. The stromal, intratumoral and total FOXP3+ TILs expression were then analyzed.RESULTS: Significant reductions in FOXP3+ TIL expression post-NAC were observed, with stromal FOXP3+ TILs showing a median decrease of 3.6 units in subjetcs aged ≥50 years (p=0.013) and a median decrease of 13.2 units in subjects with tumors ≥5 cm after NAC (p=0.006). In contrast, intratumoral FOXP3+ TILs remained relatively stable, with minor changes. The total FOXP3+ TIL expression, combining stromal and intratumoral components, was significantly decreased with a median of 13.0 units decreased to 5.3 units (p<0.001).CONCLUSION: This study highlights the significant reduction in stromal FOXP3+ TIL expression after NAC treatment in IBC-NST subjects, in contrast to the relatively stable intratumoral FOXP3+ TILs. Understanding these differences may guide future therapeutic strategies and improve treatment outcomes for IBC-NST.KEYWORDS: biomarkers, chemotherapy, FOXP3, prognostic, response, lymphocyte

Oncological outcomes of post neo adjuvant chemotherapy breast conservation surgery in patients with locally advanced breast cancer

Abstract Introduction: Breast cancer in India is phenotypically different with locally advanced breast cancers (LABCs) forming 30–50% of all cases. Use of neoadjuvant chemotherapy (NACT), among other things has contributed to surgeons using breast conservation surgery (BCS) in very selected patients with good results. Herein, we describe the oncological outcomes of BCS in LABC patients undergoing surgery post NACT. Patients and Methods: This is an ambispective observational cohort study conducted between January 1996 and December 2019 after approval by Institute Ethics Committee, to study the ipsilateral breast tumor recurrence (IBTR) in patients with LABC undergoing BCS post NACT. The secondary objectives were to ascertain the disease-free survival (DFS) and overall survival (OS) and factors associated with IBTR in these patients. Patients were staged according to the anatomic American Joint Committee on Cancer (AJCC) VIII Tumor Node Metastasis (TNM) classification and clinic-demographic, pathologic, treatment, and follow-up details were noted. Results: Out of 822 patients with LABC, 71 patients undergoing BCS post NACT were included. Average tumor size at presentation was 6.43 cm. The most common T stage was T3 (57.7%) and N stage was N1 (53.5%). The most common stage group was IIIB in 40.8%. Around 75% received anthracycline-based NACT with 28.2% having a complete clinical response. A pathological complete response was seen in 16 patients (22.5%). The mean follow-up duration was 6.14 years. A total of 25 patients had recurrences: five patients had IBTR (7%) and four had a local with regional recurrence. Two, 5, and 10 years OS were 94.0, 83.8, and 61.9%, respectively, and DFS were 87.8, 67.1, and 50.6%, respectively. A higher clinical T stage was associated with poor DFS (p = 0.01). The risk of IBTR was not found to significantly correlate with any of the standard prognostic factors. Conclusion: BCS post NACT in suitably selected patients of LABC is a safe and viable option without adversely affecting oncological outcomes.

Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial

PurposePrevious studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status.MethodsOpen-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier’s classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity.ResultsOut of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9–85.4) vs. 71.9% (95%CI: 54.6–84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8–83.2) vs. 61.5% (95%CI: 42.5–77.6), 82.4% (95%CI: 62.2–93.6) vs. 100% (95%CI: 74.1–100), and 90% (95%CI: 69.8–98.3) vs. 100% (95%CI: 74.1–100). Toxicity profile was consistent with previous reports.ConclusionOur results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned.Trial registration numberNCT02339532 (registered on 14/12/14).

Comparative analysis of breast cancer characteristics in young premenopausal and postmenopausal women in Ghana

Breast cancer is increasingly common among young women in Ghana. BCa is heterogeneous with unique traits that impact causes, prognostic, and predictive outcomes of patients before and after menopause. However, limited evidence exists on differences between young premenopausal (YPM) and postmenopausal cases in Ghana. This study compared breast tumour characteristics between YPM women (under 35 years) and postmenopausal women. We conducted a prospective cross-sectional study involving 140 BCa-diagnosed women at the Breast Care Clinic of Komfo Anokye Teaching Hospital (KATH), Kumasi from November 2019 to June 2021. Thirty-one (22.1%) of participants were YPM and 109 (77.9%) were postmenopausal. The median ages for YPM and postmenopausal were 32.0 (range: 25.0–35.0) and 57.0 (48.0–86.0) respectively. Invasive carcinoma was the most common histological type (97.1%). Left tumour location was the most frequent in both groups (51.6% for YPM and 51.8% for postmenopausal). Lumps detected were frequently in the outer upper quadrant in both groups (61.3% and 56.0%). The majority of the YPM women (80.7%) and postmenopausal women (87.0%) had stage III and IV diseases. Most YPM (64.5%) and postmenopausal women (64.4%) exhibited triple-negative breast cancer (TNBC). Both YPM 13 (56.6%) and postmenopausal participants 40 (56.3%) exhibited a predominantly partial response to neo-adjuvant chemotherapy but YPM women (21.7%) experienced disease progression than the postmenopausal women (12.7%). The study highlights consistent tumour characteristics and advanced clinical stages at diagnosis in both groups with a higher prevalence of TNBC. TNBC and HER2+ subtypes respond better to Anthracycline-based neoadjuvant chemotherapy. Establishing Breast Care Clinics in district and regional hospitals for early detection is crucial and further studies are warranted to understand the higher TNBC prevalence in black Africans and re-evaluate breast education programs to address the persistently late presentations.

CD10 expression as a potential predictor of pathological complete response in ER-negative and triple-negative breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy

BackgroundNeoadjuvant chemotherapy (NCT) can induce a pathological complete response (pCR) in breast cancer patients, leading to improved outcomes. However, predicting which patients will achieve pCR remains a challenge. CD10, a myoepithelial marker, has shown diagnostic and prognostic value in metastatic tumors. Its potential as a predictor of chemosensitivity to anthracycline-based NCT in breast cancer is unknown. AimThis retrospective study aimed to investigate the potential of CD10 cancer cell expression as a predictive marker of chemosensitivity in breast cancers treated with anthracycline-based neoadjuvant chemotherapy. MethodsWe analyzed 130 patients with invasive ductal carcinoma who received anthracycline-based NCT. CD10 expression was assessed by immunohistochemistry on pre-treatment biopsies. Statistical analysis evaluated the association between CD10 expression and pCR rates. ResultsUnivariate analysis revealed that ER-positive and CD10-negative tumors had lower pCR rates [OR 7.4830 (95% CI 2.7762–20.1699); p = 0.0001]. Multivariate analysis confirmed ER status as a strong predictor of poor response [OR 0.085 (95% CI 0.024–0.30); p < 0.001] and CD10 expression as a predictor of a favourable response [OR 0.11 (0.8–0.19); p = 0.049]. CD10 expression significantly predicted pCR in ER-negative cases [OR 0.1098 (0.0268–0.4503); p = 0.0022] and triple-negative breast cancer [OR 0.0966 (95% CI 0.0270–0.3462); p = 0.0003]. Concordance was observed between core biopsies and excised samples. ConclusionPositive CD10 cancer cell expression may predict increased response to anthracycline-based neoadjuvant chemotherapy in ER-negative and triple-negative breast cancer cases. Further research is needed to validate these findings in larger cohorts and determine the clinical utility of CD10 as a predictive marker.

The relationship between the difference neutrophil to lymphocyte ratio before and after anthracycline-based neoadjuvant chemotherapy with clinical response in locally advanced breast cancer

Link of Video Abstract: https://youtu.be/Jb1SATaI8oQ Introduction: The difference in the Neutrophil-to-Lymphocyte Ratio (NLR) before and after chemotherapy, which is commonly called the delta NLR, is thought to be a better predictive factor than pre-chemotherapy NLR or post-chemotherapy NLR in breast cancer patients. Methods: We analyzed 130 locally advanced breast cancer (LABC) patients who received anthracycline-based neoadjuvant chemotherapy (NACT) at Dr. Soetomo General Hospital Surabaya from January 2017 – December 2021. Results: Out of 130 patients, 91 (70.0%) responded to chemotherapy. Bivariate analysis showed a significant relationship between delta NLR and chemotherapy response (p = 0.002). Patients with delta NLR &lt; 0 achieved a significantly higher rate of clinical response to NACT compared to those with delta NLR ≥ 0 (OR: 4.67, 95% CI: 1.69 – 12.85, p: 0.003) Conclusion: LABC patients with delta NLR &lt; 0 have better clinical response to anthracycline-based NACT than those with delta NLR ≥ 0.

CNA Landscape of HER2-Negative Breast Cancer in Anthracycline-Based Neoadjuvant Chemotherapy Regimens.

Critical evaluation of how and when to include anthracyclines in preoperative chemotherapy is becoming more relevant in an era when the molecular genetic approach not only allows for the development of biologically targeted therapeutics, but also implies the ability to select the patients likely to benefit from certain cytotoxic agents. Changes in the copy number aberration (CNA) landscape of luminal B HER2- negative (HER2-) breast cancer (BC) during anthracycline-based neoadjuvant chemotherapy (NAC) regimens were studied in order to identify groups of potential CNA markers of objective response and CNA markers for predicting the development of hematogenous metastasis. Comparison of CNA frequencies depending on the response to NAC showed that objective response was observed in a larger number of deletions in the 11q22.3 and 11q23.1 loci (p = 0.004). Comparison of CNA frequencies in groups of patients after treatment showed that hematogenous metastasis was observed with a greater number of amplifications in the 9p22.2 locus (p = 0.003) and with a greater number of deletions in the 9p21.3 locus (p = 0.03). Potential predictive CNA markers of objective response and prognostic CNA markers of hematogenous metastasis in anthracycline- based NAC regimens have been identified.

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects. From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2- breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status. Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95-20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02-2.67; p = 0.5). This study showed that BRCA1 mutation carriers with HR+/HER2- breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.

Proof-of-concept study linking ex vivo sensitivity testing to neoadjuvant anthracycline-based chemotherapy response in breast cancer patients

We developed a functional ex vivo anthracycline-based sensitivity test. Surgical resection material of primary breast cancer (BC) was used to determine criteria for the ex vivo sensitivity assay based on morphology, proliferation and apoptosis. Subsequently, a proof-of-concept study was performed correlating results of this assay on primary BC biopsies with in vivo response after treatment with anthracycline-containing neoadjuvant chemotherapy (NAC). Cut off values for the ex vivo anthracycline-based sensitivity test were established based on analysis of 21 primary breast tumor samples obtained after surgery. In the proof-of-concept study based on a new set of tumor biopsies, 41 patients were included. Eight biopsies did not contain tumor cells and three patients could not be biopsied for various reasons. In the remaining 30 biopsies, the success rate of the ex vivo test was 77% (23/30); six out of seven failed tests were due to excessive apoptosis, our pre-specified test criteria. Of the 23 patients with a successful ex vivo test result, three patients did not undergo NAC after the biopsy. Here we report the ex vivo anthracycline-based sensitivity assay is feasible on biopsy material and shows 75% concordance between ex vivo outcomes and in vivo MRI response. Unfortunately, the percentage of unsuccessful tests is rather high. This study provides the foundation for further development of ex vivo sensitivity assays.

Evaluating the expression of heat shock protein 27 and topoisomerase II α in a retrospective cohort of patients diagnosed with locally advanced breast cancer and treated with neoadjuvant anthracycline-based chemotherapies.

Neoadjuvant anthracycline-based chemotherapy (NAC) is a major regimen for the treatment of local advanced breast cancer (LABC), while resistance to NAC remains a paramount clinical obstacle. To investigate the role of heat shock protein 27 (Hsp27) and/or topoisomerase IIα (TopoIIα) in LABC patients treated with NAC, we performed this retrospective study. Associations of Hsp27 transcripts with clinic-pathological characteristics, survival and drug response were investigated in public databases. Hsp27-related genes were identified, followed by functional enrichment analyses. Besides, two protein-protein interaction networks were built. Then, tumors from 103 patients who were diagnosed with LABC and received NAC were collected, and Hsp27 and TopoIIα were examined by Immunohistochemistry (IHC). Chi-square or Fisher's exact tests were performed, as well as survival analyses. Either at the transcriptional level in public databases or at the protein level tested by IHC, a high level of Hsp27 was associated with aggressive tumor characteristics such as lymph node invasion and chemotherapy resistance. Hsp27-related genes mostly involved in the metabolic pathway and the gamete generation biological process. An elevated Hsp27 indicated a poor prognosis in patients with breast cancer (log-rank test P = 0.002 and 0.004 for disease-free survival [DFS] and overall survival [OS], respectively), while it might not be an independent predictor. Of note, tumors with high TopoIIα expression (TopoIIα+) was less likely to express Hsp27 (Hsp27+), in contrast to those with TopoIIα negativity (31.1% vs. 86.2%, P<0.001), and survival analyses revealed that patients with Hsp27+ and TopoIIα- tumors had a significantly lower DFS and OS (log-rank test P < 0.001 and 0.001, respectively), in contrast to the other three groups. Hsp27 was associated with aggressive breast cancers and more predictable for the prognosis of LABC patients treated with NAC when concomitantly considering TopoIIα expression.

Deep learning with whole slides images to predict histological response to neoadjuvant chemotherapy in patients with resectable high grade soft-tissue sarcomas: A multicenter study.

11512 Background: Two recent randomized trials have confirmed the potential benefit of neoadjuvant anthracycline-based chemotherapy in patients with high-grade soft-tissue sarcomas (STS) (Issels et al 2018, Gronchi et al 2017). However, as for adjuvant chemotherapy, the main issue with neoadjuvant treatment of STS patients is the identification of predictive factors of response to chemotherapy that could avoid for a majority of patients ineffective and potentially toxic treatment with impaired quality of life. Histological response, defined as the percentage of stainable tumor cells on the surgical specimen, has been shown to be a reliable surrogate for metastasis-free survival and overall survival in bone but also in soft-tissue sarcomas (Crombe et al JCO Clin Inf 2021). Developing a tool to help medical oncologists predict the potential benefit of neoadjuvant chemotherapy prior to starting the treatment would be of great value for precision medicine in sarcomas. To address this need, we propose a deep learning-based approach to predict histological response to neoadjuvant chemotherapy patients from routine histological whole slide images sampled at diagnosis. Methods: A cohort of 220 patients with high grade limb and trunk wall STS enrolled in the NEOSARCOMICS study (NCT02789384, sponsor: Institut Bergonié, Bordeaux, France) was used to train a model to predict the binarized histological response from diagnostic biopsies. Responders are defined by a histological response inferior or equal to 10%. Digitized hematoxylin/eosin slides were preprocessed to segment the tissue and decompose the image into patches of smaller resolution. Features were extracted from each patch using a Vision Transformer pretrained in a self-supervised fashion on histology slides. A Multiple Instance Learning model was trained on the resulting features to compute a prediction at the patient level. The algorithm was trained and validated through a 5-fold, 5-repeat cross-validation scheme. Finally, external validation is performed on an unseen cohort from Centre Léon Bérard to assess the robustness of the model. Results: To predict histological response to neoadjuvant chemotherapy, a model using only diagnostic biopsies achieved an AUC of 0.69 (95% confidence interval, 0.60-0.76). External validation is ongoing and shows promising preliminary results with an AUC of 0.67 (95% confidence interval with bootstrapping, 0.45-0.89). Conclusions: This multi-center study demonstrates that deep-learning models can accurately predict the histological response to neoadjuvant chemotherapy from routine histological whole slide images sampled at diagnosis. This model could be used as a pre-screening tool to improve patient selection for neoadjuvant chemotherapy in STS.

Tumour necrosis factor-alpha levels as predictor factor on clinical response of anthracycline-based neoadjuvant chemotherapy in locally advance breast cancer patients: experimental research.

Analysing TNF-α levels as a predictor factor on clinical response anthracycline-based neoadjuvant chemotherapy. This study design used observational analysis. The length of study was carried out in the period from May 2021 to June 2022. The study procedure included measuring participants' TNF-α levels the day before chemotherapy was carried out and clinical response. Participants received anthracycline-based neoadjuvant chemotherapy (cyclophosphamide of 500mg/m2, doxorubicin of 50mg/m2 and fluorouracil/5FU of 500mg/m2) for 3 cycles. The study analysis used the Chi-square, logistic regression and Spearman's test with P<0.05. The average TNF-α levels was 137.2±311.8pg/ml, ranging from 5.74 to 1.733pg/ml. The results of the calculation of the cutoff value of TNF-α in the study were 18635pg/ml (area under curve =0.850; 95% CI =0.729-0.971). Based on cutoff 1, most participants with high TNF-α levels also had a negative response of 83.3% and those with low TNF-α levels also had a positive response of 75% (P<0.001). Meanwhile, at cutoff 2, similar conditions were also found, namely high TNF-α levels, negative response (84.2%) and low TNF-α levels, positive response (78.9%; P<0.001). The statical analysis showed a significant association of TNF-α levels on the clinical response of chemotherapy, which showed r=-0.606 and P<0.001. TNF-α levels predict clinical response for anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer patients.

Prognostic and Predictive Value of LIV1 Expression in Early Breast Cancer and by Molecular Subtype.

LIV1 is a transmembrane protein that may become a new therapeutic target through the development of antibody-drug conjugates (ADCs). Few studies are available regarding the assessment of LIV1 expression in clinical breast cancer (BC) samples. We analyzed LIV1 mRNA expression in 8982 primary BC. We searched for correlations between LIV1 expression and clinicopathological data, including disease-free survival (DFS), overall survival (OS), pathological complete response to chemotherapy (pCR), and potential vulnerability and actionability to anti-cancer drugs used or under development in BC. Analyses were performed in the whole population and each molecular subtype separately. LIV1 expression was associated with good-prognosis features and with longer DFS and OS in multivariate analysis. However, patients with high LIV1 expression displayed a lower pCR rate than patients with low expression after anthracycline-based neoadjuvant chemotherapy, including in multivariate analysis adjusted on grade and molecular subtypes. LIV1-high tumors were associated with higher probabilities of sensitivity to hormone therapy and CDK4/6 inhibitors and lower probabilities of sensitivity to immune-checkpoint inhibitors and PARP inhibitors. These observations were different according to the molecular subtypes when analyzed separately. These results may provide novel insights into the clinical development and use of LIV1-targeted ADCs by identifying prognostic and predictive value of LIV1 expression in each molecular subtype and associated vulnerability to other systemic therapies.

The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

BMI and TLC increase Neoadjuvant Chemotherapy Response in Patients with Locally Advanced Breast Cancer

Anthracycline-based neoadjuvant chemotherapy is the recommended therapy for locally advanced breast cancer (LABC) patients. Unfortunately, no study has reported the relationship between body mass index (BMI), total lymphocyte count (TLC), and responses to this type of chemotherapy. This study aimed to determine the relationship between BMI, TLC, and response to doxorubicin/epirubicin neoadjuvant chemotherapy in LABC patients. A retrospective cohort design was applied to medical records of LABC patients undergoing neoadjuvant chemotherapy at Ulin General Hospital Banjarmasin, Indonesia, from July to December 2021. BMI and TLC data were assessed based on the values before chemotherapy, while the chemotherapy response was measured using the RECIST 1.1 criteria after 3 cycles. Multinomial logistic regression test with 95% confidence level was used to analyze these data. The results showed that as many as 71% of patients experienced a Partial Response (PR), while 5% and 23% of the patients demonstrated Stable Disease (SD) and Progressive Disease (PD), respectively. Each increase in BMI of 1 kg/m2 was significantly associated with an increase in the occurrence of PR and PD by 1.26 times and 1.29 times, respectively, when compared to the occurrence of PD. Meanwhile, an increase in TLC of 100 cells/mm3 was associated with an increase in the occurrence of PR by 6.83 times and an increase in the occurrence of SD. of 6.94 when compared to the occurrence of PD. Therefore, there is a significant relationship between BMI, TLC, and response to anthracycline-based neoadjuvant chemotherapy in LABC patients

Abstract 9729: Pulling Out All the Stops (for a Diagnosis): A Case of Progressive Dyspnea

A 63-year-old woman with hypertension, diabetes mellitus, severe obesity, obstructive sleep apnea, and history of GATA3+/ER+ breast cancer treated 14 years prior with neoadjuvant anthracycline-based chemotherapy and subsequent lumpectomy, chest radiotherapy, and letrozole presented to the emergency department with three weeks of progressive cough and exertional dyspnea. Physical examination revealed tachypnea, hypoxemia, a prominent P2, and jugular venous distension with a Kussmaul sign. Further investigation showed moderate hemolytic anemia, severe thrombocytopenia, and elevated natriuretic peptides. Electrocardiography revealed normal sinus rhythm, an S1Q3T3 pattern, and diffuse T wave inversions. Computed tomography angiography of the chest was notable for few small pulmonary nodules and diffuse vertebral osteosclerosis, consistent with osteoblastic metastases. Transthoracic echocardiography exhibited a moderately dilated RV with moderate systolic dysfunction, moderate TR, and an estimated RVSP of 79 mm Hg. Lung perfusion scintigraphy disclosed subtle subsegmental defects. Right heart catheterization (RHC) showed elevated right-sided filling pressures and severe precapillary pulmonary hypertension (RA 12 mm Hg, mPAP 51 mm Hg, PCWP 6 mm Hg, and PVR 775 dynes-sec/cm 5 ). There was no discernable shunt. These findings, coupled with the patient’s history, rapidly progressive symptoms, and hematologic derangements, raised suspicion for pulmonary tumor thrombotic microangiopathy (PTTM). A pulmonary capillary wedge blood aspirate was sent for cytology. Her clinical status rapidly worsened despite inhaled pulmonary vasodilators, hemodynamic support, and systemic glucocorticoids, precluding candidacy for empirical chemotherapy. She was transitioned to comfort measures only and suffered a bradycardic PEA arrest on hospital day 8. Autopsy was declined. Cytological analysis of the wedge blood aspirate ultimately revealed clusters of neoplastic GATA3+ cells, consistent with PTTM associated with late recurrence of breast carcinoma. This case highlights the rare instance of PTTM diagnosis aided by wedge cytology, reinforcing the multidimensional role of RHC in this extremely uncommon and devastating clinical entity.

Association of neutrophil-lymphocyte ratio (NLR) with the anthracycline-based neoadjuvant chemotherapy (NAC) clinical response in locally advanced breast cancer (LABC) in young women

Background: Breast cancer in young women is one of the leading causes of cancer death in young women worldwide, including in Indonesia. Most patients come to the hospital at the advanced stage. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. However, half of breast cancer patients had a negative response to therapy. &#x0D; Methods: A retrospective cohort, analytic observational study to determine the association between NLR and anthracycline-based NAC clinical response in locally advanced young age breast cancer in Dr. Soetomo General Hospital, Surabaya.&#x0D; Results: We analyze a total of 44 patients. 81.8% had stage IIIB, 93.2% &gt;50 mm tumor size. Most of the cases had invasive ductal carcinoma type (86.4%), grade 3 (52.3%), and Luminal B HER2-negative type (34.1%). 52.3% of patients had a negative clinical response. The mean NLR was 3.07 ± 1.69, with a cut-off value of 2.805. There was no significant association between age, tumor size, histopathological type, grade, and subtype with neoadjuvant chemotherapy clinical response. There was a significant relationship between NLR with anthracycline-based NAC clinical response in locally advanced young age breast cancer (p &lt; 0.001).&#x0D; Conclusion: There was a significant relationship between NLR with the anthracycline-based neoadjuvant chemotherapy clinical response in young women with LABC.

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis

BackgroundData guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment. Materials and MethodsThere were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS). ResultsMedian follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes. ConclusionIn this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer

We examined whether 18F-fluorodeoxyglucose metabolism is associated with distant relapse-free survival (DRFS) and overall survival (OS) in women with estrogen receptor (ER)-positive, HER2-negative breast cancer. This was a cohort study examining the risk factors for survival that had occurred at the start of the study. A cohort from Asan Medical Center, Korea, recruited between November 2007 and December 2014, was included. Patients received anthracycline-based neoadjuvant chemotherapy. The maximum standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was measured. The analysis included 466 women. The median (interquartile range) follow-up period without distant metastasis or death was 6.2 (5.3–7.6) years. Multivariable analysis of hazard ratio (95% confidence interval [CI]) showed that the middle and high tertiles of SUV were prognostic for DRFS (2.93, 95% CI 1.62–5.30; P < 0.001) and OS (4.87, 95% CI 1.94–12.26; P < 0.001). The 8-year DRFS rates were 90.7% (95% CI 85.5–96.1%) for those in the low tertile of maximum SUV vs. 73.7% (95% CI 68.0–79.8%) for those in the middle and high tertiles of maximum SUV. 18F-fluorodeoxyglucose PET/CT may assess the risk of distant metastasis and death in ER-positive, HER2-negative patients.

Association of P-glycoprotein expression and response to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer

BACKGROUND Neoadjuvant chemotherapy (NACT) has been shown to improve the overall survival of locally advanced breast cancer (LABC) patients with pathological complete response. However, the efficacy may be reduced due to chemoresistance mediated by P-glycoprotein (Pgp). This study aimed to explore the association between Pgp expression and patients’ response to NACT.&#x0D; METHODS A prospective cohort study was carried out from May 2018 to October 2019 at Cipto Mangunkusumo Hospital and Koja Hospital. Treatment-naïve LABC patients were consecutively enrolled in the study. Immunohistochemistry analysis of the biopsy samples was done to semi-quantitatively measure Pgp expression. The clinical response was evaluated after 3 cycles of NACT, while the pathological response was evaluated for subjects who underwent surgery post-NACT.&#x0D; RESULTS Mean age of the subjects was 46.2 (9.6) years old, and most of the cases were invasive ductal (78%) and luminal B subtype (61%). Pgp was strongly expressed in 21/27 subjects (78%). There were no differences between Pgp-positive and -negative subjects for clinical response (relative risk [RR] 1.1, 95% confidence interval [CI] 0.33–4.01, p = 0.61) and pathological response (RR 1.3, 95% CI 0.8–1.9, p = 0.22). Other clinicopathologic variables were not associated with either clinical or pathological responses.&#x0D; CONCLUSIONS These results showed that Pgp is expressed in most LABC patients, but its role as a predictive factor could not be established. However, due to the limited subjects and a lack of standardized Pgp measurement, careful consideration must be done when interpreting these results.