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Abstract Triple-negative breast cancer (TNBC) is often treated with neoadjuvant systemic therapy (NAST). We investigated if radiomic models based on multiparametric Magnetic Resonance Imaging (MRI) obtained early during NAST predict pathologic complete response (pCR). We included 163 patients with stage I-III TNBC with multiparametric MRI at baseline and after 2 (C2) and 4 cycles of NAST. Seventy-eight patients (48%) had pCR, and 85 (52%) had non-pCR. Thirty-six multivariate models combining radiomic features from dynamic contrast-enhanced MRI and diffusion-weighted imaging had an area under the receiver operating characteristics curve (AUC) > 0.7. The top-performing model combined 35 radiomic features of relative difference between C2 and baseline; had an AUC = 0.905 in the training and AUC = 0.802 in the testing set. There was high inter-reader agreement and very similar AUC values of the pCR prediction models for the 2 readers. Our data supports multiparametric MRI-based radiomic models for early prediction of NAST response in TNBC.

El cáncer mamario impacta en diversas esferas de la vida del paciente y su entorno familiar y social. Se trata de una enfermedad compleja que requiere un abordaje multidisciplinario tanto para el diagnóstico como para el tratamiento, así como en lo relativo al manejo de la toxicidad mediata y tardía del tratamiento sistémico y la radioterapia y también los aspectos psicológicos. Los cuidados paliativos y el manejo del dolor se incorporan cada vez más tempranamente al tratamiento en beneficio de los pacientes. Actualmente se ha incorporado a los genetistas a este abordaje multidisciplinario debido a los avances en genotipificación y terapias dirigidas. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario y el objetivo de este artículo es el presentar la actualización en el manejo multidisciplinario del cáncer de mama.

El cáncer de mama es la neoplasia más frecuente y con mayor mortalidad en mujeres en todo el mundo. La décima actualización del Consenso Mexicano Sobre Diagnóstico y Tratamiento del Cáncer Mamario (2023) es publicada por sus autores en diferentes artículos. El presente artículo incluye el manejo de cáncer de mama avanzado, el tratamiento sistémico adyuvante, el papel de la cirugía y la radioterapia en enfermedad metastásica y el seguimiento posterior al tratamiento con intención curativa. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario en etapas avanzadas.

Objective:Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer.Materials and Methods:Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated.Results:Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups.Conclusion:Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

El cáncer mamario en estadios tempranos tiene un manejo local (quirúrgico y radioterapia) y sistémico específico. Este tipo de cáncer incluye el carcinoma ductal in situ y los cánceres de mama en estadios I, IIA, IIB y IIIA. Esta décima actualización del Consenso Mexicano de Cáncer Mamario abordó el manejo de los estadios tempranos. La difusión de este consenso contribuye a la actualización y homogeneidad de criterios de manejo del cáncer mamario y el objetivo de este artículo es presentar la actualización en el manejo multidisciplinario del cáncer de mama.

Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions of interest were segmented on DCE images at baseline (BL) and after two (C2) and four (C4) cycles of NAST. Ten first-order (FO) radiomic features and 300 gray-level-co-occurrence matrix (GLCM) features were calculated. Area under the receiver operating characteristic curve (AUC) and Wilcoxon rank sum test were used to determine the most predictive features. Multivariate logistic regression models were used for performance assessment. Pearson correlation was used to assess intrareader and interreader variability. Seventy-eight patients (48%) had pCR (52 training, 26 testing), and 85 (52%) had non-pCR (57 training, 28 testing). Forty-six radiomic features had AUC at least 0.70, and 13 multivariate models had AUC at least 0.75 for training and testing sets. The Pearson correlation showed significant correlation between readers. In conclusion, Radiomic features from DCE-MRI are useful for differentiating pCR and non-pCR. Similarly, predictive radiomic models based on these features can improve early noninvasive treatment response prediction in TNBC patients undergoing NAST.

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Neoadjuvant systemic therapy (NAST) followed by surgery are currently standard of care for TNBC with 50-60% of patients achieving pathologic complete response (pCR). We investigated ability of deep learning (DL) on dynamic contrast enhanced (DCE) MRI and diffusion weighted imaging acquired early during NAST to predict TNBC patients’ pCR status in the breast. During the development phase using the images of 130 TNBC patients, the DL model achieved areas under the receiver operating characteristic curves (AUCs) of 0.97 ± 0.04 and 0.82 ± 0.10 for the training and the validation, respectively. The model achieved an AUC of 0.86 ± 0.03 when evaluated in the independent testing group of 32 patients. In an additional prospective blinded testing group of 48 patients, the model achieved an AUC of 0.83 ± 0.02. These results demonstrated that DL based on multiparametric MRI can potentially differentiate TNBC patients with pCR or non-pCR in the breast early during NAST.

Background: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway. Objective: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether PTEN copy number variation (CNV) by next-generation sequencing (NGS) can serve as an alternative to immunohistochemistry (IHC) to identify PTEN loss. Methods: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and PTEN CNV by NGS was also performed. Results: With a stringent cutoff for PTEN IHC scoring, PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients ( n = 96) and between posttreatment primary tumors and lymph node metastases in 9% ( n = 33). A less stringent cutoff yielded similar discordance rates. Intratumoral heterogeneity for PTEN loss was observed in 7% of the patients. Among pretreatment tumors, PTEN copy numbers by whole exome sequencing ( n = 72) were significantly higher in the PTEN-positive tumors by IHC compared with the IHC PTEN-loss tumors ( p

Abstract In the ATEMPT trial, adjuvant trastuzumab emtansine (T-DM1) compared to paclitaxel plus trastuzumab (TH) for stage I HER2-positive breast cancer improved patient-reported outcomes (PROs), while maintaining excellent disease outcomes. We report treatment discontinuation and use multivariable models to compare, patient-reported toxicity and quality-of-life (QOL) by age (≤50, >50) and treatment arm at 18 months post-enrollment among 366 eligible participants randomized in a 3:1 ratio to T-DM1 or TH. T-DM1 discontinuation was higher among women >50 vs. ≤50 (23% vs. 9%, p = 0.003, Fisher’s Exact test) with 4%, 8%, and 17% of older patients discontinuing treatment by 3, 6, and 9 months, respectively. Superior QOL with T-DM1 vs. TH was observed among women ≤50 with estimated mean difference of 6.48 (95% confidence interval (CI) 0.51–12.46) and driven by better social/family well-being and breast cancer-specific sub-scores. Among women >50, T-DM1 was associated with superior physical well-being and less activity impairment, with no differences in global QOL. Older women had decreased neuropathy with T-DM1 vs. TH. De-escalated treatment regimens for HER2 positive breast cancer may have age-varying impact on treatment tolerance, toxicities and subsequent QOL, which should be considered when selecting therapy options. Clinical Trial Registration: ClinicalTrials.gov, NCT01853748

Accurate tumor segmentation is required for quantitative image analyses, which are increasingly used for evaluation of tumors. We developed a fully automated and high-performance segmentation model of triple-negative breast cancer using a self-configurable deep learning framework and a large set of dynamic contrast-enhanced MRI images acquired serially over the patients’ treatment course. Among all models, the top-performing one that was trained with the images across different time points of a treatment course yielded a Dice similarity coefficient of 93% and a sensitivity of 96% on baseline images. The top-performing model also produced accurate tumor size measurements, which is valuable for practical clinical applications.

Abstract The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3–4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed. Clinical Trial Registration: ClinicalTrials.gov, NCT01853748

There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. Using a deep learning model (DLM), a metabolite panel consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with improved pathologic complete response (pCR) in triple-negative breast cancer (TNBC). We hypothesize that integrating high sTILs and additional clinicopathologic features associated with pCR could enhance our ability to predict the group of patients on whom treatment de-escalation strategies could be tested. In this prospective early-stage TNBC neoadjuvant chemotherapy study, pretreatment biopsies from 408 patients were evaluated for their clinical and demographic features, as well as biomarkers including sTILs, Ki-67, PD-L1 and androgen receptor. Multivariate logistic regression models were developed to generate a computed response score to predict pCR. The pCR rate for the entire cohort was 41%. Recursive partitioning analysis identified ≥20% as the optimal cutoff for sTILs to denote 35% (143/408) of patients as having high sTILs, with a pCR rate of 59%, and 65% (265/408) of patients as having low sTILs, with a pCR rate of 31%. High Ki-67 (cutoff > 35%) was identified as the only predictor of pCR in addition to sTILs in the training set. This finding was verified in the testing set, where the highest computed response score encompassing both high sTILa and high Ki-67 predicted a pCR rate of 65%. Integrating Ki67 and sTIL may refine the selection of early stage TNBC patients for neoadjuvant clinical trials evaluating de-escalation strategies.

Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease, accounting for 2–4% of new cases of breast cancer. Owing to its aggressive nature, IBC represent approximately 8–10% of breast cancer deaths. Management of IBC requires a multidisciplinary team for decision-making involving a composite of systemic treatment, surgery, and radiation, or “Trimodality Treatment.” Because of the rarity of the disease, systemic therapy of IBC traditionally has been extrapolated from non-IBC clinical trials. Aim of Review: The purpose of this review is to provide an overview of the development of systemic treatment of IBC from the past to the present by focusing on IBC clinical trials, including chemotherapy and targeted therapies. Key Scientific Concepts of Review: We discuss their effects on pathologic complete response (pCR) and survival outcomes, the predictive markers, and the adverse events of these therapies. Further, we summarized the current standard treatment stratified by molecular subtypes based on clinical data. Finally, we discuss the future trend of systemic therapy, including immunotherapy and ongoing IBC clinical trials.

Abstract The development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.

Circulating tumor cells (CTCs) are indicators of metastatic spread and progression. In a longitudinal, single-center trial of patients with metastatic breast cancer starting a new line of treatment, a microcavity array was used to enrich CTCs from 184 patients at up to 9 timepoints at 3-month intervals. CTCs were analyzed in parallel samples from the same blood draw by imaging and by gene expression profiling to capture CTC phenotypic plasticity. Enumeration of CTCs by image analysis relying primarily on epithelial markers from samples obtained before therapy or at 3-month follow-up identified the patients at the highest risk of progression. CTC counts decreased with therapy, and progressors had higher CTC counts than non-progressors. CTC count was prognostic primarily at the start of therapy in univariate and multivariate analyses but had less prognostic utility at 6 months to 1 year later. In contrast, gene expression, including both epithelial and mesenchymal markers, identified high-risk patients after 6–9 months of treatment, and progressors had a shift towards mesenchymal CTC gene expression on therapy. Cross-sectional analysis showed higher CTC-related gene expression in progressors 6–15 months after baseline. Furthermore, patients with higher CTC counts and CTC gene expression experienced more progression events. Longitudinal time-dependent multivariate analysis indicated that CTC count, triple-negative status, and CTC expression of FGFR1 significantly correlated with inferior progression-free survival while CTC count and triple-negative status correlated with inferior overall survival. This highlights the utility of protein-agnostic CTC enrichment and multimodality analysis to capture the heterogeneity of CTCs.

Early assessment of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) is critical for patient care in order to avoid the unnecessary toxicity of an ineffective treatment. We assessed functional tumor volumes (FTVs) from dynamic contrast-enhanced (DCE) MRI after 2 cycles (C2) and 4 cycles (C4) of NAST as predictors of response in TNBC. A group of 100 patients with stage I-III TNBC who underwent DCE MRI at baseline, C2, and C4 were included in this study. Tumors were segmented on DCE images of 1 min and 2.5 min post-injection. FTVs were measured using the optimized percentage enhancement (PE) and signal enhancement ratio (SER) thresholds. The Mann–Whitney test was used to compare the performance of the FTVs at C2 and C4. Of the 100 patients, 49 (49%) had a pathologic complete response (pCR) and 51 (51%) had a non-pCR. The maximum area under the receiving operating characteristic curve (AUC) for predicting the treatment response was 0.84 (p < 0.001) for FTV at C4 followed by FTV at C2 (AUC = 0.82, p < 0.001). The FTV measured at baseline was not able to discriminate pCR from non-pCR. FTVs measured on DCE MRI at C2, as well as at C4, of NAST can potentially predict pCR and non-pCR in TNBC patients.

Abstract Background The PI3K/AKT pathway is activated through PIK3CA or AKT1 mutations and PTEN loss in breast cancer. We conducted a phase II trial with an allosteric AKT inhibitor MK-2206 in patients with advanced breast cancer who had tumors with PIK3CA/AKT1 mutations and/or PTEN loss/mutation. Methods The primary endpoint was objective response rate (ORR). Secondary endpoints were 6-month progression-free survival (6 m PFS), predictive and pharmacodynamic markers, safety, and tolerability. Patients had pre-treatment and on-treatment biopsies as well as collection of peripheral blood mononuclear cells (PBMC) and platelet-rich plasma (PRP). Next-generation sequencing, immunohistochemistry, and reverse phase protein arrays (RPPA) were performed. Results Twenty-seven patients received MK-2206. Eighteen patients were enrolled into the PIK3CA/AKT1 mutation arm (cohort A): 13 had PIK3CA mutations, four had AKT1 mutations, and one had a PIK3CA mutation as well as PTEN loss. ORR and 6 m PFS were both 5.6% (1/18), with one patient with HR+ breast cancer and a PIK3CA E542K mutation experiencing a partial response (on treatment for 36 weeks). Nine patients were enrolled on the PTEN loss/mutation arm (cohort B). ORR was 0% and 6 m PFS was 11% (1/9), observed in a patient with triple-negative breast cancer and PTEN loss. The study was stopped early due to futility. The most common adverse events were fatigue (48%) and rash (44%). On pre-treatment biopsy, PIK3CA and AKT1 mutation status was concordant with archival tissue testing. However, two patients with PTEN loss based on archival testing had PTEN expression on the pre-treatment biopsy. MK-2206 treatment was associated with a significant decline in pAKT S473 and pAKT T308 and PI3K activation score in PBMC and PRPs, but not in tumor biopsies. By IHC, there was no significant decrease in median pAKT S473 or Ki-67 staining, but a drop was observed in both responders. Conclusions MK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations or PTEN loss. This may, in part, be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation, as well as tumor heterogeneity and evolution in markers such as PTEN conferring challenges in patient selection. Trial registration ClinicalTrials.gov, NCT01277757. Registered 13 January 2011.

BackgroundThe current use of targeted therapy plus neoadjuvant chemotherapy for inflammatory breast cancer (IBC) is based on data extrapolated from studies in non-IBC. We conducted a systematic review to determine whether neoadjuvant chemotherapy plus targeted therapy results in a higher pathologic complete response (pCR) rate than neoadjuvant chemotherapy alone in patients with IBC.Method and findingsThis systematic review was registered in the PROSPERO register with registration number CRD42018089465. We searched MEDLINE & PubMed, EMBASE, and EBSCO from December 1998 through July 2020. All English-language clinical studies, both randomized and non-randomized, that evaluated neoadjuvant systemic treatment with or without targeted therapy before definitive surgery and reported the pCR results of IBC patients. First reviewer extracted data and assessed the risk of bias using the Risk of Bias In Non-randomized Studies of Interventions tool. Second reviewer confirmed the accuracy. Studies were divided into 3 groups according to systemic treatment: chemotherapy with targeted therapy, chemotherapy alone, and high-dose chemotherapy with hematopoietic stem cell support (HSCS). Of 995 screened studies, 23 with 1,269 IBC patients met the inclusion criteria. For each of the 3 groups of studies, we computed a weighted average of the pCR rates across all studies with confidence interval (CI). The weighted averages (95% CIs) were as follows: chemotherapy with targeted therapy, 31.6% (26.4%-37.3%), chemotherapy alone, 13.0% (10.3%-16.2%), and high-dose chemotherapy with HSCS, 23.0% (18.7%-27.7%). The high pCR by targeted therapy group came from anti-HER2 therapy, 54.4% (44.3%-64.0%). Key limitations of this study included no randomized clinical studies that included only IBC patients.ConclusionNeoadjuvant chemotherapy plus targeted therapy is more effective than neoadjuvant chemotherapy alone for IBC patients. These findings support current IBC standard practice in particular the use of anti-HER2 targeted therapy.

High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR after neoadjuvant chemotherapy (NACT). In this prospective NACT study, pretreatment biopsies from 318 patients with early-stage TNBC were evaluated for sTILs. Recursive partitioning analysis (RPA) was applied to search for the sTIL cutoff best associated with a pCR. With ≥20% sTILs identified as the optimal cutoff, 33% patients had high sTILs (pCR rate 64%) and 67% had low sTILs (pCR rate 29%). Patients were stratified according to the sTIL cutoff (low vs. high) and response to NACT (pCR vs. residual disease (RD)). The primary endpoint was event-free survival (EFS), with hazard ratios calculated using the Cox proportional hazards regression model and the 3-year restricted mean survival time (RMST) as primary measures. Within the high-sTIL group, EFS was better in patients with a pCR compared with those with RD (HR 0.05; 95% CI 0.01–0.39; p = 0.004). The difference in the 3-year RMST for EFS between the two groups was 5.6 months (95% CI 2.3–8.8; p = 0.001). However, among patients with RD, EFS was not significantly different between those with high sTILs and those with low sTILs (p = 0.7). RNA-seq analysis predicted more CD8+ T cells in the high-sTIL group with favorable EFS compared with the high-sTIL group with unfavorable EFS. This study did not demonstrate that high baseline sTILs confer a benefit in EFS in the absence of a pCR.

BackgroundTumor cells with a mesenchymal phenotype and/or cancer stem-like cells (CSCs) are known to contribute to metastasis and drug resistance. Circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT) and CTCs reflecting a dedifferentiated CSC phenotype may not be detected using only an anti-EpCAM antibody to capture them. We used an antibody-independent CTC enrichment platform, ApoStream®, which does not rely on any antibody, including anti-EpCAM, to capture EMT- and CSC-CTCs in breast cancer patients who received neoadjuvant chemotherapy and correlated them to pathological complete response (pCR).MethodsBlood samples from newly diagnosed breast cancer patients were prospectively collected before neoadjuvant chemotherapy (T0), after chemotherapy but before surgery (T1), and after surgery (T2) and processed using ApoStream. CTCs detected were stained with additional markers to define 3 CTC subsets with the following phenotypes: epithelial CTCs (CK+, EpCAM+ or E-cadherin+), EMT-CTCs (β-catenin+ or vimentin+), and CSC-CTCs (CD44+ and CD24low).ResultsWe enrolled 55 patients, 47 of which had data for analysis. EMT-CTCs were detected in 57%, 62%, and 72% and CSC-CTCs in 9%, 22%, and 19% at the T0, T1, and T2 time points, respectively. Counts of epithelial (P = 0.225) and EMT (P = 0.522) phenotypes of CTCs at T0 did not significantly predict pCR. Moreover, no correlation between CTC count change and pCR was demonstrated.ConclusionsApoStream was successful in detecting EMT-CTCs among patients after neoadjuvant chemotherapy. However, EMT-/CSC-CTC counts did not correlate with pCR. Due to the small sample size and heterogeneity of this patient population, further study in a larger cohort of molecularly homogeneous patients is warranted.

Background: We retrospectively evaluated the correlation between a baseline measurement of circulating tumor cells (CTCs) and inflammation-based scores in patients with metastatic breast cancer (MBC). Methods: The optimal value of inflammation-based scores as the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) to predict survival was determined and compared with CTC 1 versus 1), tumor subtypes (triple-negative versus HER2– ER+ tumors) and MLR only remained significant. Conclusions: CTC and MLR are predictors of overall survival in MBC. CTC correlates with monocytes, in particular in triple-negative tumors.

The AJCC updated its breast cancer staging system to incorporate biological factors in the “prognostic stage”. We undertook this study to validate the prognostic and anatomic stages for inflammatory breast cancer (IBC). We established two cohorts of IBC diagnosed without distant metastasis: (1) patients treated at The University of Texas MD Anderson Cancer Center between 1991 and 2017 (MDA cohort) and (2) patients registered in the national Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 (SEER cohort). For prognostic staging, estrogen receptor (ER)+/progesterone receptor (PR)+/ human epidermal growth factor receptor-2 (HER2)+/grade 1–2 was staged as IIIA; ER+/PR−/HER2−/grade 3, ER−/PR+/HER2−/grade 3, and triple-negative cancers as IIIC; and all others as IIIB. Endpoints were breast cancer-specific survival (BCSS), overall survival (OS), and disease-free survival (DFS). We studied 885 patients in the MDA cohort and 338 in the SEER cohort. In the MDA cohort, the prognostic stage showed significant predictive power for BCSS, OS, and DFS (all p < 0.0001), although the anatomic stage did not. In both cohorts, the Harrell concordance index (C index) was significantly higher in the prognostic stage than the anatomic stage for all endpoints. In conclusion, the prognostic stage provided more accurate prognostication for IBC than the anatomic stage. Our results show that the prognostic staging is applicable in IBC.

BACKGROUND:To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center. METHODS:Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data. RESULTS:Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P

Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT.

Altered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).In this prospective study, we measured miR-21, miR-10b, and miR-19a levels using quantitative reverse transcriptase-polymerase chain reaction in the serum of 113 breast cancer patients and determined their association with clinicopathologic factors and clinical outcome. Thirty healthy donors with no history of cancer were enrolled as controls.Patients with non-metastatic HER2(+) breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2(-) disease (p = 0.044); whereas patients with metastatic HER2(+) breast cancer had higher serum miR-10b median levels than patients with metastatic HER2(-) disease (p = 0.0004). There were no significant differences in serum miR-19a median levels between HER2(+) and HER2(-) groups, regardless of the presence of metastases. High serum miR-19a levels were associated with IBC (p = 0.039). Patients with metastatic IBC had significantly higher serum miR-19a median levels than patients with metastatic non-IBC (p = 0.019). Finally, high serum miR-19a levels were associated with longer progression-free survival time (10.3 vs. 3.2 months; p = 0.022) and longer overall survival time (median not reached vs. 11.2 months; p = 0.003) in patients with metastatic HER2(+) IBC.High levels of miR-21 and miR-10b were present in the serum of patients with non-metastatic and metastatic HER2(+) breast cancer, respectively. High levels of serum miR-19a may represent a biomarker for IBC that is predictive for favorable clinical outcome in patients with metastatic HER2(+) IBC.