Treatment Options For Breast Cancer Research Articles

Abstract P2-15-09: Impact of neoadjuvant chemotherapy on the short- and long-term outcomes in patients who underwent immediate breast reconstruction after mastectomy

Abstract Background and Purpose In breast cancer patients receiving neoadjuvant chemotherapy (NAC), the use of immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. The Japanese breast cancer society conducted retrospective multicenter cohort study in the era of IBR, and we assessed the impact of NAC on surgical and oncological outcomes in patients underwent IBR. Methods Between January 2008 and December 2016, 473 (10.0%) breast cancer cases received NAC of 4726 cases underwent IBR after mastectomy. The clinicopathological and survival data of patients who received NAC (the NAC group) and those who did not receive NAC (the control group) were compared in terms of postoperative complications (infection, hemorrhage, seroma, dehiscence, tissue expander or implant loss, flap or skin necrosis) and oncologic safety. Results Eight-hundred forty cases had minor or major complications. NAC did not increase the risk of complications after IBR (OR 1.20; 95%CI 0.95 - 1.53; p = 0.13). Smoking (OR 1.35; 95%CI 1.14 - 1.62; p = 0.001), overweight (BMI25≤) (OR 1.94; 95%CI 1.61 - 2.35; p < 0.001), PMRT (OR 1.54; 95%CI 1.20 - 1.99; p = 0.01) increased risk of complications. At the median follow-up time of 76.5 months, 36 patient (7.6%) in the NAC group and 147 patients (3.5%) in the control group had local recurrence. 35 patient (7.4%) in the NAC group and 147 patients (2.0%) in the control group had reginal recurrence. Conclusion Immediate breast reconstruction after NAC is a safe procedure with post-operative complication profile. It can be performed safely and therefore should be considered as a strategy preferred for patients with local advanced breast cancer. Citation Format: Hiroko Nogi, Akiko ogiya, Naoto Kondo, Makoto Ishitobi, Chikako Yamauchi, Hiroki Mori, Ayaka Shimo, Kazutaka Narui, Naomi Nagura, Hirohito Seki, Shinsuke Sasada, Teruhisa Sakurai, Tadahiko Shien. Impact of neoadjuvant chemotherapy on the short- and long-term outcomes in patients who underwent immediate breast reconstruction after mastectomy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-09.

Phospholipid-Based Topical Nano-Hydrogel of Mangiferin: Enhanced Topical Delivery and Improved Dermatokinetics.

Mangiferin is a herbal drug that has proven anticancer potential. Owing to its lower aqueous solubility and poor oral bioavailability, the full pharmacological potential of this bioactive drug has not fully been explored. In the present study, phospholipid-based microemulsion systems were developed to bypass oral delivery. The globule size of the developed nanocarriers was less than 150 nm and the drug entrapment was >75% with a drug loading ~25%. The developed system offered a controlled release pattern following the Fickian drug release. This enhanced mangiferin's in vitro anticancer activity by four-fold, the cellular uptake was observed to be improved by three-fold on the MCF-7 cells. Ex vivo dermatokinetic studies showed substantial topical bioavailability with a prolonged residence time. The findings provide a simple technique to administer mangiferin via a topical route promising a safer, topically bioavailable and effective treatment option for breast cancer. Such scalable carriers with immense topical delivery potential may provide a better option for present-day topical products of a conventional nature.

Mechanistic modeling of metastatic relapse in early breast cancer to investigate the biological impact of prognostic biomarkers

Background and objectiveEstimating the risk of metastatic relapse is a major challenge to decide adjuvant treatment options in early-stage breast cancer (eBC). To date, distant metastasis-free survival (DMFS) analysis mainly relies on classical, agnostic, statistical models (e.g., Cox regression). Instead, we propose here to derive mechanistic models of DMFS. MethodsThe present series consisted of eBC patients who did not receive adjuvant systemic therapy from three datasets, composed respectively of 692 (Bergonié Institute), 591 (Paoli-Calmettes Institute, IPC), and 163 (Public Hospital Marseille, AP-HM) patients with routine clinical annotations. The last dataset also contained expression of three non-routine biomarkers. Our mechanistic model of DMFS relies on two mathematical parameters that represent growth (α) and dissemination (μ). We identified their population distributions using mixed-effects modeling. Critically, we propose a novel variable selection procedure allowing to: (i) identify the association of biological parameters with either α, μ or both, and (ii) generate an optimal candidate model for DMFS prediction. ResultsWe found that Ki67 and Thymidine Kinase-1 were associated with α, and nodal status and Plasminogen Activator Inhibitor-1 with μ. The predictive performances of the model were excellent in calibration but moderate in discrimination, with c-indices of 0.72 (95% CI [0.48, 0.95], AP-HM), 0.63 ([0.44, 0.83], Bergonié) and 0.60 (95% CI [0.54, 0.80], IPC). ConclusionsOverall, we demonstrate that our novel method combining mechanistic and advanced statistical modeling is able to unravel the biological roles of clinicopathological parameters from DMFS data.

IRAK2 Downregulation in Triple-Negative Breast Cancer Cells Decreases Cellular Growth In Vitro and Delays Tumour Progression in Murine Models

Breast cancer stem cells (BCSCs) are responsible for tumour recurrence and therapy resistance. We have established primary BCSC cultures from human tumours of triple-negative breast cancer (TNBC), a subgroup of breast cancer likely driven by BCSCs. Primary BCSCs produce xenografts that phenocopy the tumours of origin, making them an ideal model for studying breast cancer treatment options. In the TNBC cell line MDA-MB-468, we previously screened kinases whose depletion elicited a differentiation response, among which IRAK2 was identified. Because primary BCSCs are enriched in IRAK2, we wondered whether IRAK2 downregulation might affect cellular growth. IRAK2 was downregulated in primary BCSCs and MDA-MB-468 by lentiviral delivery of shRNA, causing a decrease in cellular proliferation and sphere-forming capacity. When orthotopically transplanted into immunocompromised mice, IRAK2 knockdown cells produced smaller xenografts than control cells. At the molecular level, IRAK2 downregulation reduced NF-κB and ERK phosphorylation, IL-6 and cyclin D1 expression, ERN1 signalling and autophagy in a cell line-dependent way. Overall, IRAK2 downregulation decreased cellular aggressive growth and pathways often exploited by cancer cells to endure stress; therefore, IRAK2 may be considered an interesting target to compromise TNBC progression.

Grounded Practical Theory Analysis of Patient-Provider Communication with Black Women Participating in Breast Cancer Clinical Trials

Background:Previous literature suggests breast cancer clinical trial participation among Black women has declined in recent years by as much as 35%. Though the literature identifies barriers to participation for this population, little has been studied about how researchers can address these barriers. This study investigates the communication between healthcare providers and Black women to reveal how providers and researchers can positively influence their perceptions of breast cancer clinical trial participation.Methods:Fourteen women (n=14) who self-identified as Black, Black American, or African American, were interviewed about their communication experiences with healthcare providers regarding breast cancer clinical trial participation. Each transcribed interview was coded using thematic analysis. Grounded Practical Theory was introduced to give insight into the patient-provider communication needs of Black breast cancer research participants.Findings:The findings fell into four categories: (1) impressions of participants toward their providers, (2) reflections on the clinical trial recruitment experience, (3) communication relationships with medical and research providers, and (4) cultural aspects of patient-provider communication. One major finding was that an important way women learn about clinical trials is through conversations with their oncologists. However, only 29% of Black women interviewed were informed of their clinical trial by a healthcare provider, suggesting that Black women may not be receiving the information they need to participate in clinical trials.Conclusion:By understanding existing patient-provider communication typologies, we can improve these methods of communication to increase the interest and participation of Black women in breast cancer clinical trials.Implications:Clinical trials provide data to healthcare providers about treatment options for breast cancer. If minoritized populations are continually underrepresented in clinical trials, these treatments might not prove to be efficacious in Black women. Researchers must make the necessary investment of resources and effort to better understand the needs of Black women in clinical trial recruitment.

The Association Between Mammography Screening Frequency and Breast Cancer Treatment and Outcomes: A Retrospective Cohort Study.

Guidelines for optimal frequency of screening mammography vary by professional society. Sparse evidence exists on the association between screening frequency and breast cancer treatment options. The main objective was to examine differences in cancer treatment rendered for U.S. women with different numbers of screenings prior to breast cancer diagnosis. Cancer stage at diagnosis and health care cost were assessed in secondary analyses. This IRB-exempt retrospective study used administrative claims data to identify women aged 44 or older with various numbers of mammographic screenings ≥11 months apart, during the four years prior to incident breast cancer diagnosis from January 2010 to December 2018. Outcomes were assessed over the six months following diagnosis. Generalized linear regression models were used to compare women with differing numbers of mammograms, adjusting for patient characteristics. Claims data review identified 25 492 women who met inclusion criteria. There was a stepwise improvement in each of these screening categories such that women with four screenings, compared to women with only one screening, experienced higher rates of lumpectomy (70% vs 55%) and radiation therapy (48% vs 36%), lower rates of mastectomy (27% vs 34%) and chemotherapy (28% vs 36%), less stage 3 or 4 cancer at diagnosis (15% vs 29%), and lower health care costs within six months postdiagnosis (P < 0.001). Results were similar in a subgroup limited to women aged 44 to 49 at diagnosis. Potential benefits of more frequent screening include less aggressive treatment and lower health care costs among women who develop breast cancer.

A study on concurring effect of paclitaxel and thymoquinone on MCF-7 cell line – In vitro

Background: Breast cancer is notorious for causing mortality and morbidity in most of the cancer patients which is spread to approximately 19.3 million people worldwide. Out of the various drugs available to treat breast cancers, thymoquinone (TMQ) and Paclitaxel (PCT) are known to have significant effects in varied mechanisms. However, only a limited literature is available to prove the activity when given as combined therapy. This opens a new arena for investigations to explore the efficacy of the combined drugs. As a result, a combination of these drugs may be a viable and risk-free treatment option for breast cancer. Aims and Objectives: The present research was designed to evaluate the individual anti-cancer effects of TMQ and PCT to their combined effects on MCF-7 breast cancer cell lines in an effort to enhance the disease’s therapeutic profile. Materials and Methods: Breast cancer (MCF-7) cell lines were cultured and incubated after exposure to the drugs in Dulbecco’s modified Eagle’s medium and MTT assay was conducted to determine the cell viability at 540 nm in UV spectroscopy. IC50 individual drugs treated groups TMQ and PCT and combined treatment group (TMQ + PCT) were determined using cell viability graph. Results: Results showed that the IC50 of TMQ was 31.2 μg/mL, PCT was 57.28 μg/ml, and TMQ + PCT were 4.20 μg/mL which proves the significant activity of the combined drug therapy using combination of TMQ and PCT on MCF-7 cell lines. Conclusion: This work enables researchers to investigate the potential for synergism between several anticancer medications to establish effective choices for the treatment of breast cancer with a fewer side effects.

The effect of using adjuvant aromatase inhibitors on cognitive functions in postmenopausal women with hormone receptor-positive breast cancer.

Breast cancer is the most frequently diagnosed cancer in women worldwide. Aromatase inhibitors (AIs) are effective treatment options for both early-stage and advanced hormone receptor-positive breast cancer. Because of AIs are used long term in adjuvant therapy, side effects are also very important. It is considered that AIs may affect cognitive functions by decreasing the level of estrogen in the brain. The purpose of our study is that evaluate the relationship between duration of treatment and cognitive functions in patients with breast cancer who use AIs in adjuvant therapy. Two-hundred patients diagnosed with breast cancer who were treated with AIs as adjuvant treatment were included. The patients were surveyed for demographic characteristics. Montreal Cognitive Assessment (MoCA) and Standardized Mini-Mental State Examination (SMMT) tests were performed to evaluate patients' cognitive functions. The total scores of the tests and the orientation, short-time memory, visuospatial functions, attention, language, executive functions which are the MoCA subscales were evaluated separately. Patients were grouped as 0-6, 6-12, 12-24, 24-36, 36, and more months according to the duration of AIs using time. The total MoCA and SMMT scores were affected by factors such as age, education level, and employment status. There was no relationship between duration of treatment and cognitive functions in patients with breast cancer who use AIs in adjuvant therapy (P > 0.05). In addition, no statistically relationship was found in the evaluation of MoCA subscales (P > 0.05). Prolonged adjuvant treatment with AIs does not affect cognitive functions in hormone receptor-positive breast cancer patients.

Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis.

The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood-brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. Since natural medicine has been a key inspiration for the development of the majority of current medicines, in this paper, we review several naturally-derived molecules which have the potential for immunotherapy via blocking the interaction of programmed cell death protein-1 (PD-1) and its ligand, PD-L1. The mechanism of action, physicochemical properties and pharmacokinetics of these molecules and their theoretical potential to be used for the treatment of TNBC-BM are discussed.

Apoptosis, Proliferation, and Autophagy Are Involved in Local Anesthetic-Induced Cytotoxicity of Human Breast Cancer Cells.

Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

New treatment options for metastatic HER2-low breast cancer : Consequences for histopathological diagnosis.

The overexpression of HER2 in breast cancer is aclassic example for molecular targeted therapy, and it has been shown that classical anti-HER2 therapeutics were only effective in patients with HER2 overexpressing tumors. Therefore, in recent decades, pathologists have been focused on the reliable identification of HER2 overexpressing tumors. Based on the results of recent clinical trials in metastatic breast cancer with antibody-drug conjugates (ADCs), this diagnostic strategy for evaluation of HER2 is currently changing. It has been shown that the ADC trastuzumab-deruxtecan is effective not only against tumors with classical HER2 overexpression, but also against HER2-low tumors. These clinical trial results lead to aparadigm shift in the treatment of patients whose tumours were previously classified as HER2 negative. In addition to the identification of HER2 (score3+) overexpressing tumors, it is necessary to identify HER2-low expressing tumors (defined as an immunohistochemistry (IHC) score of1+ or IHC2+ with negative in situ hybridization).Due to the therapeutic consequences, it is important to quickly adapt the diagnostic workup and reporting to the new requirements. In addition, the new therapeutic options for anti-HER2 therapy lead to new challenges for standardization as well as to new scientific questions for the characterization of tumors with low HER2 expression.

Association of BRCAness with taxane resistance in triple-negative breast cancer: A study of 7 cases

Introduction: Chemotherapy is the only systemic treatment option for triple-negative breast cancer (TNBC) patients, and is often used in combination with anthracycline and taxane. However, it was reported that many TNBCs show BRCA dysfunction, and are sensitive to DNA-damaging agents, but tend to be resistant to mitotic poisons, such as taxanes. Case Series: Triple-negative breast cancer patients who underwent neoadjuvant chemotherapy with anthracycline followed by taxane were analyzed. Clinical responses to taxane were evaluated by the percentage of shrinkage in tumor size after anthracycline treatment. BRCAness was analyzed by mutiplex ligation-dependent probe amplification (MLPA) in core-needle biopsy specimens of 7 patients with progressive disease or stable disease after taxane treatment. BRCAness scores of the 7 patients were between 0.779 and 1.000 (0.939 ± 0.084), and all were categorized as having BRCAness. Conclusion: Patients resistant to taxane were categorized as having BRCAness by MLPA. Mutiplex ligation-dependent probe amplification may hence be a promising method to identify TNBC patients with taxane resistance.

Tissue and liquid biopsy profiling reveal convergent tumor evolution and therapy evasion in breast cancer

Pathological and genomic profiling have transformed breast cancer care by matching patients to targeted treatments. However, tumors evolve and evade therapeutic interventions often through the acquisition of genomic mutations. Here we examine patients profiled with tissue (TBx) and liquid biopsy (LBx) as part of routine clinical care, to characterize the tumor evolutionary landscape and identify potential vulnerabilities in the relapsed setting. Real-world evidence demonstrates that LBx is utilized later in care and identifies associations with intervening therapy. While driver events are frequently shared, acquired LBx alterations are detected in a majority of patients, with the highest frequency in ER+ disease and in patients with longer biopsy intervals. Acquired mutations are often polyclonal and present at lower allelic fractions, suggesting multi-clonal convergent evolution. In addition to well-characterized resistance mutations (e.g., ESR1, NF1, RB1, ERBB2), we observe a diversity of rarer but potentially targetable mutations (e.g., PIK3CA, HRAS/NRAS/KRAS, FGFR1/2/3, BRAF) and fusions (e.g., FGFR1/2, ERBB2, RET), as well as BRCA1/2 reversions through a variety of mechanisms, including splice alterations and structural deletions. This study provides insights on treatment and selection-driven tumor evolution and identifies potential combinatorial treatment options in advanced breast cancer.

Prognostic effect of HER2 evolution from primary breast cancer to breast cancer metastases

PurposeTherapeutic options for breast cancer (BC) treatment are constantly evolving. The Human Epidermal Growth Factor 2 (HER2)-low BC entity is a new subgroup, representing about 55% of all BC patients. New antibody–drug conjugates demonstrated promising results for this BC subgroup. Currently, there is limited information about the conversion of HER2 subtypes between primary tumor and recurrent disease.MethodsThis retrospective study included women with BC at the University Medical Centre Wuerzburg from 1998 to 2021. Data were retrieved from patients' records. HER2 evolution from primary diagnosis to the first relapse and the development of secondary metastases was investigated.ResultsIn the HR-positive subgroup without HER2 overexpression, HER2-low expression in primary BC was 56.7 vs. 14.6% in the triple-negative subgroup (p < 0.000). In the cohort of the first relapse, HER2-low represented 64.1% of HR-positive vs. 48.2% of the triple-negative cohort (p = 0.03). In patients with secondary metastases, HER2-low was 75.6% vs. 50% in the triple negative subgroup (p = 0.10). The subgroup of HER2-positive breast cancer patients numerically increased in the course of disease; the HER2-negative overall cohort decreased. A loss of HER2 expression from primary BC to the first relapse correlated with a better OS (p = 0.018). No clinicopathological or therapeutic features could be identified as potential risk factors for HER2 conversion.ConclusionHER2 expression is rising during the progression of BC disease. In view of upcoming therapeutical options, the re-analysis of newly developed metastasis will become increasingly important.

The Present and Future of Clinical Management in Metastatic Breast Cancer.

Regardless of the advances in our ability to detect early and treat breast cancer, it is still one of the common types of malignancy worldwide, with the majority of patients decease upon metastatic disease. Nevertheless, due to these advances, we have extensively characterized the drivers and molecular profiling of breast cancer and further dividing it into subtypes. These subgroups are based on immunohistological markers (Estrogen Receptor-ER; Progesterone Receptor-PR and Human Epidermal Growth Factor Receptor 2-HER-2) and transcriptomic signatures with distinct therapeutic approaches and regiments. These therapeutic approaches include targeted therapy (HER-2+), endocrine therapy (HR+) or chemotherapy (TNBC) with optional combination radiotherapy, depending on clinical stage. Technological and scientific advances in the identification of molecular pathways that contribute to therapy-resistance and establishment of metastatic disease, have provided the rationale for revolutionary targeted approaches against Cyclin-Dependent Kinases 4/6 (CDK4/6), PI3 Kinase (PI3K), Poly ADP Ribose Polymerase (PARP) and Programmed Death-Ligand 1 (PD-L1), among others. In this review, we focus on the comprehensive overview of epidemiology and current standard of care treatment of metastatic breast cancer, along with ongoing clinical trials. Towards this goal, we utilized available literature from PubMed and ongoing clinical trial information from clinicaltrials.gov to reflect the up to date and future treatment options for metastatic breast cancer.

Tissue Expression of Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Breast Cancers.

Breast cancer is the most common cancer among women worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) has important roles in immunity, cell proliferation, and carcinogenesis. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein also known as hepatitis A virus cellular receptor 1 and T-cell immunoglobulin and mucin, has restricted expression in immune cells and healthy epithelial cells, but it is up-regulated in several human cancers. The aim of this study was to determine the prognostic values of NGAL and KIM-1 expression in tumor cells and to detect the presence of NGAL-positive neutrophils (PNL) in the tumor microenvironment. The expression of NGAL and KIM-1 protein were assessed by immunohistochemical staining in tissue specimens from 412 primary breast cancer cases. In this series, the mean age of the patients was 55.6±12.4 years. In 218 (52.9%) cases, there was NGAL expression in tumor cells. In 104 (25.2%) cases there was KIM-1 expression in tumor cells. NGAL-positive inflammatory cells were seen in tumors of 45 (10.9%) cases. There was no significant relationship between NGAL-positive PNL presence in the tumor microenvironment and other clinicopathological features. However, there was a significant association between the presence of in situ carcinomas and NGAL expression (p = 0.008) and KIM-1 expression (p = 0.020) in tumor cells. This study has demonstrated positivity of NGAL and KIM-1 in breast cancer cells. Considering the development of anti-KIM-1 therapies, the presence of KIM-1 expression may be a new treatment option in breast cancer, especially in in situ component-rich tumors. These findings should be confirmed in larger series.

Zinc transporter LIV1: A promising cell surface target for triple negative breast cancer.

Breast cancer is one of the leading causes contributing to the global cancer burden. The triple negative breast cancer (TNBC) molecular subtype accounts for the most aggressive type. Despite progression in therapeutic options and prognosis in breast cancer treatment options, there remains a high rate of distant relapse. With advancements in understanding the role of zinc and zinc carriers in the prognosis and treatment of the disease, the scope of precision treatment/targeted therapy has been expanded. Zinc levels and zinc transporters play a vital role in maintaining cellular homeostasis, tumor surveillance, apoptosis, and immune function. This review focuses on the zinc transporter, LIV1, as an essential target for breast cancer prognosis and emerging treatment options. Previous studies give an insight into the role of LIV1 in fulfilling the most important hallmarks of cancer such as apoptosis, metastasis, invasion, and evading the immune system. Normal tissue expression of LIV1 is limited. Higher expression of LIV1 has been linked to Epithelial-Mesenchymal Transition, histological grade of cancer, and early node metastasis. LIV1 was found to be one of the attractive targets in the therapeutic hunt for TNBCs. TNBCs are an immunogenic breast cancer subtype. As zinc transporters are known to serve as the metabolic gatekeepers of immune cells, this review bridges tumor infiltrating lymphocytes, TNBC and LIV1. In addition, the suitability of LIV1 as an antibody-drug conjugate (Seattle genetics [SGN]-LIV1A) target in TNBC, represents a promising strategy for patients. Early clinical trial results reveal that this novel agent reduces tumor burden by inducing mitotic arrest, immunomodulation, and immunogenic cell death, warranting further investigation of SGN-LIV1A in combination with immuno-oncology agents. Priming the patient's immune response in combination with SGN-LIV1A could eventually change the landscape for the TNBC patient population.

Comparative efficacy and safety of first-line neoadjuvant treatments in triple-negative breast cancer: systematic review and network meta-analysis.

Neoadjuvant treatment options for triple-negative breast cancer (TNBC) are abundant, but the efficacy of different combinations of treatment options remains unclear. Our network meta-analysis aimed to evaluate the effectiveness and safety of various neoadjuvant treatment options in patients with TNBC. Literature reports published before March 31, 2022, were retrieved from the PubMed, Embase, Cochrane Library, main oncology conference of the European Society of Medical Oncology, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium databases. Pairwise and Bayesian network meta-analyses were performed to compare direct and indirect evidence, respectively. The primary outcome was pathological complete response (pCR). Comparison of efficiency between different treatment regimens was made by HRs and 95% confidence intervals (CIs). Overall, 26 studies, including 9714 TNBC patients, were assessed in this network meta-analysis. Results indicated that the pCR of immune checkpoint inhibitors plus platinum-containing regimens is better than other joint regimens. PCR rate of neoadjuvant chemotherapy regimens containing bevacizumab, platinum, poly(ADP-ribose) polymerase inhibitors, and immune checkpoint inhibitors was higher than those of standard chemotherapy agents. By performing a conjoint analysis of the pCR rate and safety endpoints, we found that immune checkpoint inhibitors plus platinum-containing regimens were well balanced in terms of efficacy and toxicity. Considering the efficacy and acceptable adverse events, neoadjuvant chemotherapy based on immune checkpoint inhibitors plus platinum may be considered as an option for patients with TNBC.

ASO Author Reflections: Is Breast-Conserving Surgery a Safe Treatment Option for High-Risk Breast Cancer?

ASO Author Reflections: Is Breast-Conserving Surgery a Safe Treatment Option for High-Risk Breast Cancer?

68MO Generalization of a deep learning model for HER2 status predictions on H&amp;E-stained whole slide images derived from 3 neoadjuvant clinical studies

Due to its decisive role to select targeted treatment options in breast cancer, we investigated if machine learning (ML) models could identify HER2-positive tumours from routinely obtained haematoxylin and eosin (H&E)-stained whole slide images.