Residual Cancer Burden Research Articles

Quantitative DCE-MRI prediction of breast cancer recurrence following neoadjuvant chemotherapy: a preliminary study

IntroductionBreast cancer patients treated with neoadjuvant chemotherapy (NACT) are at risk of recurrence depending on clinicopathological characteristics. This preliminary study aimed to investigate the predictive performances of quantitative dynamic contrast-enhanced (DCE) MRI parameters, alone and in combination with clinicopathological variables, for prediction of recurrence in patients treated with NACT.MethodsForty-seven patients underwent pre- and post-NACT MRI exams including high spatiotemporal resolution DCE-MRI. The Shutter-Speed model was employed to perform pharmacokinetic analysis of the DCE-MRI data and estimate the Ktrans, ve, kep, and τi parameters. Univariable logistic regression was used to assess predictive accuracy for recurrence for each MRI metric, while Firth logistic regression was used to evaluate predictive performances for models with multi-clinicopathological variables and in combination with a single MRI metric or the first principal components of all MRI metrics.ResultsPre- and post-NACT DCE-MRI parameters performed better than tumor size measurement in prediction of recurrence, whether alone or in combination with clinicopathological variables. Combining post-NACT Ktrans with residual cancer burden and age showed the best improvement in predictive performance with ROC AUC = 0.965.ConclusionAccurate prediction of recurrence pre- and/or post-NACT through integration of imaging markers and clinicopathological variables may help improve clinical decision making in adjusting NACT and/or adjuvant treatment regimens to reduce the risk of recurrence and improve survival outcome.

Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial.

IntroductionIn early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT.MethodThe Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582).Expected resultsIf Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.

Dynamic Changes in the NK-, Neutrophil-, and B-cell Immunophenotypes Relevant in High Metastatic Risk Post Neoadjuvant Chemotherapy-Resistant Early Breast Cancers.

To identify potential immune targets in post-neoadjuvant chemotherapy (NAC)-resistant triple-negative breast cancer (TNBC) and ER+HER2- breast cancer disease. Following pathology review, 153 patients were identified as having residual cancer burden (RCB) II/III disease (TNBC n = 80; ER+HER2-n = 73). Baseline pre-NAC samples were available for evaluation for 32 of 80 TNBC and 36 of 73 ER+HER2- cases. Bright-field hematoxylin and eosin assessment allowed for tumor-infiltrating lymphocyte (TIL) evaluation in all cases. Multiplexed immunofluorescence was used to identify the abundance and distribution of immune cell subsets. Levels of checkpoints including PD-1/PD-L1 expression were also quantified. Findings were then validated using expression profiling of cancer and immune-related genes. Cytometry by time-of-flight characterized the dynamic changes in circulating immune cells with NAC. RCB II/III TNBC and ER+HER2- breast cancer were immunologically "cold" at baseline and end of NAC. Although the distribution of immune cell subsets across subtypes was similar, the mRNA expression profiles were both subtype- and chemotherapy-specific. TNBC RCB II/III disease was enriched with genes related to neutrophil degranulation, and displayed strong interplay across immune and cancer pathways. We observed similarities in the dynamic changes in B-cell biology following NAC irrespective of subtype. However, NAC induced changes in the local and circulating tumor immune microenvironment (TIME) that varied by subtype and response. Specifically, in TNBC residual disease, we observed downregulation of stimulatory (CD40/OX40L) and inhibitory (PD-L1/PD-1) receptor expression and an increase in NK cell populations (especially non-cytolytic, exhausted CD56dimCD16-) within both the local TIME and peripheral white cell populations. This study identifies several potential immunologic pathways in residual disease, which may be targeted to benefit high-risk patients.

ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer

BackgroundHigh-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). ObjectiveTo determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. Design, setting, and participantsARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. InterventionPatients were randomly assigned at a 1:1 ratio to degarelix (240–80–80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. Outcome measurements and statistical analysisThe primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. Results and limitationsPatients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5–11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p < 0.0001) than patients without PTEN loss. Following neoadjuvant hormonal therapy, PSMA PET–estimated tumor volumes (1.2 vs 2.5 ml, p = 0.01) and maximum standardized uptake value (SUVmax; 4.3 vs 5.7, p = 0.007) were lower in patients with MRD than in patients without MRD. PSMA PET–estimated volume and PSMA PET SUVmax following neoadjuvant treatment correlated significantly with RCB at final pathology (both p < 0.001). ConclusionsIn high-risk PCa patients, neoadjuvant degarelix plus apalutamide prior to RP results in a significantly improved pathological response (MRD and RCB) compared with degarelix alone. Our trial results provide a solid hypothesis-generating basis for neoadjuvant phase 3 trials, which are powered to detect differences in long-term oncological outcome following neoadjuvant androgen receptor signaling inhibitor therapy. Patient summaryIn this study, we looked at the difference in pathological responses in high-risk prostate cancer patients treated with degarelix plus apalutamide or degarelix plus matching placebo prior to radical prostatectomy. We demonstrated that patients treated with degarelix plus apalutamide achieved a significantly better tumor response than patients treated with degarelix plus matching placebo. Long-term follow-up is required to determine whether improved pathological outcome translates into better oncological outcomes.

ASO Visual Abstract: Does Residual Cancer Burden Predict Local Recurrence after Neoadjuvant Chemotherapy?

ASO Visual Abstract: Does Residual Cancer Burden Predict Local Recurrence after Neoadjuvant Chemotherapy?

The Impact of Tumor Infiltrating Lymphocytes Densities and Ki67 Index on Residual Breast Cancer Burden following Neoadjuvant Chemotherapy.

To avoid unnecessary neoadjuvant chemotherapy in case anticipating a poor therapy response, it is essential to find the pathological parameters that would predict pathological complete response or at least a decrease in tumor burden following neoadjuvant chemotherapy. The purpose of this study is to investigate the hypothesis that tumor infiltrating lymphocytes can predict the efficacy of neoadjuvant chemotherapy and to find the Ki67 cutoff value that best predicts the benefit of chemotherapy. 153 cases of breast cancer were chosen, based on their molecular subtype: triple negative subtype (77) and luminal, HER2-ve subtype (76). Histopathological assessment of pretherapy core biopsies was conducted to assess variable pathological parameters including TILs rates with the aid of immunohistochemical staining for CD20 and CD3. Moreover, core biopsies were stained for Ki67, and the findings were compared to the residual cancer burden following neoadjuvant chemotherapy. On analyzing and contrasting the two groups, a significant association between molecular subtype and pathological complete response was confirmed, while tumor-infiltrating lymphocytes in either group had no effect on therapy response. We used receiver operating characteristic curve analysis to determine that a cutoff of 36% for Ki67 is the most accurate value to predict complete therapy response.

Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS). To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response. The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence. Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. The presence of DCIS and EFS, DRFS, and LRR. The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS. The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS. ClinicalTrials.gov Identifier NCT01042379.

ASO Visual Abstract: Residual Cancer Burden Class Associated with Survival Outcomes in Women with Different Phenotypic Subtypes of Breast Cancer After Neoadjuvant Chemotherapy.

ASO Visual Abstract: Residual Cancer Burden Class Associated with Survival Outcomes in Women with Different Phenotypic Subtypes of Breast Cancer After Neoadjuvant Chemotherapy.

Improving prediction of response to neoadjuvant treatment in patients with breast cancer by combining liquid biopsies with multiparametric MRI: protocol of the LIMA study – a multicentre prospective observational cohort study

IntroductionThe response to neoadjuvant chemotherapy (NAC) in breast cancer has important prognostic implications. Dynamic prediction of tumour regression by NAC may allow for adaption of the treatment plan before completion,...

Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer.

This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review.

141MO Pathological response and early survival data according to TNBCtype4 classifier in operable triple-negative breast cancer (TNBC) treated with neoadjuvant carboplatin and docetaxel

141MO Pathological response and early survival data according to TNBCtype4 classifier in operable triple-negative breast cancer (TNBC) treated with neoadjuvant carboplatin and docetaxel

Measurement of Residual Breast Cancer Burden after Neoadjuvant Chemotherapy

Aim: To determine the frequency of residual cancer burden after neoadjuvant chemotherapy for breast cancer patients undergoing surgery. Study Design: Descriptive study. Place and Duration of Study: Department of Surgery, Dr. Ruth K.M. Pfau Civil Hospital Karachi from 8th May 2019 to 7th November 2019. Methodology: One hundred and twenty six females aged 25 to 75 years with stage IIA, IIB and IIIA were enrolled. Patients who had received standard protocol of neoadjuvant chemotherapy from outside i.e. six cycles of fluorouracil, anthracycline and cyclophosphomide (FAC) every 3 weeks and for HER2+ tumors, FAC was followed by 12 cycles of Trastuzumab every 3 weeks were included. Data regarding tumor characteristic, age, HER 2 status, PR status, KI 67status and nodal involvement was noted. Results: The mean age was 47.32±13 years and mean cancer cellularity was 14.88±10.4%. Nuclear grade III was present in 39.7% patients and 48.4% patients belonged to T1 stage. Majority of patients were menopausal. FAC regime was used in 58.7% patients. RCB I (minimal residual disease) was present in 12.7% patients, RCB II (moderate residual disease) was present in 51.6% patients and RCB III (extensive residual disease) was found in 35.7% patients. Cross tabulation for age, T stage, pathological AJCC classification, histological classification and nuclear grading was not significant (p&gt;0.05). Conclusion: Neoadjunctive therapy is associated with decrease rate of residual cancer burden. Keywords: Breast carcinoma. Neo adjunctive therapy, Decreases residual cancer burden

Residual Cancer Burden Class Associated with Survival Outcomes in Women with Different Phenotypic Subtypes of Breast Cancer After Neoadjuvant Chemotherapy

The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability. We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index. Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively). The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low.

ASO Author Reflections: Residual Cancer Burden Across Phenotypic Subtypes.

ASO Author Reflections: Residual Cancer Burden Across Phenotypic Subtypes.

Stromal Tumor Infiltrating Lymphocytes (sTIL) as an Independent Predictor of Pathologic Response to Neadjuvant Chemotherapy in Breast Cancer in Indonesia: A Hospital-based Study.

We aim to describe the sTIL profiles of Indonesian breast cancer patient and its role in predicting neoadjuvant chemotherapy response. This retrospective cohort study used secondary data from the archive of Anatomic Pathology Department FMUI/CMH. We did total sampling of 62 cases of locally advanced breast cancer cases that were biopsied, had neoadjuvant chemotherapy, and operated on from 2015 to 2020. We collected the clinicopathological data of each sample, measured the sTIL intensity in the biopsy specimen and evaluated the chemotherapy response from the mastectomy specimen using residual cancer burden (RCB) scoring method. Multivariate linear regression determined the independent predictors of RCB score. There were 62 female patients, 45.2% were Luminal-HER2-, 43.5% were HER2+, and 11.3% were triple negative (TN). Most sTIL intensity (59.7%) were low (median 10%; 1%-60%). Moderate-high sTIL intensity was associated with HER2+ type, while low sTIL was with luminal-HER2- (p=0.038). Only 8.1% patients achieved pCR. Statistically different median sTIL intensity in minimal, moderate, and extensive burden group were 28%, 20%, and 8%, respectively (p=0.002). sTIL was an independent predictor for better response (lower RCB score), which were 0.07 (95% CI 0.04-0.09) lower for every 1% increase in sTIL intensity. sTIL intensity was mostly low in Indonesian breast cancer patient. However, it can predict neoadjuvant chemotherapy response, with 0.07 lower RCB score for every 1% increase of sTIL intensity.

Prospective Evaluation of Ultrafast Breast MRI for Predicting Pathologic Response after Neoadjuvant Therapies.

Background Ultrafast dynamic contrast-enhanced (DCE) MRI parameters are associated with breast cancer aggressiveness. However, the role of these parameters as predictive biomarkers for pathologic response after neoadjuvant chemotherapy (NAC) has been poorly investigated. Purpose To assess whether semiquantitative perfusion parameters calculated at initial ultrafast DCE MRI are associated with early prediction for pathologic response after NAC in participants with breast cancer. Materials and Methods This prospective single-center study included consecutive women with nonmetastatic invasive breast cancer treated with NAC followed by surgery who underwent initial ultrafast DCE MRI between December 2020 and August 2021. Six semiquantitative ultrafast DCE MRI parameters were calculated for each participant from the fitted time-signal intensity curve. Multivariable logistic regression was used to identify independent predictors of pathologic complete response (pCR) and residual cancer burden (RCB). Results Fifty women (mean age, 49 years ± 12 [SD]) were included in the study; 20 achieved pCR and 25 achieved low RCB (RCB-0 and I). A wash-in slope (WIS) cutoff value of 1.6% per second had a sensitivity of 94% (17 of 18 participants) and a specificity of 59% (19 of 32 participants) for pCR. A WIS of more than 1.6% per second (odds ratio [OR], 8.4 [95% CI: 1.5, 48.2]; P = .02), human epidermal growth factor receptor 2 (HER2) positivity (OR, 6.3 [95% CI: 1.5, 27.4]; P = .01), and tumor-infiltrating lymphocytes of more than 10% (OR, 6.9 [95% CI: 1.3, 37.7]; P = .03) were independent predictive factors of pCR. The area under the receiver operating characteristic curve of the three-component model, which included WIS, tumor-infiltrating lymphocytes, and HER2 positivity, was 0.92 (95% CI: 0.84, 0.99). A WIS of more than 1.6% per second was associated with higher pCR rates in the HER2-positive (OR, 21.7 [95% CI: 1.8, 260.6]; P = .02) breast cancer subgroup. For luminal HER2-negative and triple-negative breast cancers, a WIS of more than 1.6% per second was associated with low RCB (OR, 11.0 [95% CI: 1.1, 106.4]; P = .04). Conclusion The wash-in slope (WIS) assessment at initial ultrafast dynamic contrast-enhanced MRI may be used to predict pathologic complete response (pCR) in participants with breast cancer. The WIS value was used to identify two subsets of human epidermal growth factor receptor 2-positive cancers with distinct pCR rates. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Moy in this issue.

Biomarker Dynamics and Long-Term Treatment Outcomes in Breast Cancer Patients with Residual Cancer Burden after Neoadjuvant Therapy.

A residual cancer burden after neoadjuvant therapy (NAT) for breast cancer (BC) is associated with worse treatment outcomes compared to patients who achieved pathologic complete remission. This single-institutional retrospective study of 767 consecutive patients, including 468 patients with assessable residual cancer burden (aRCB) after NAT, with a median follow-up of 36 months, evaluated the biomarkers assessed before NAT from a biopsy and after NAT from a surgical specimen, their dynamics, and effect on long-term outcomes in specific breast cancer subtypes. The leading focus was on proliferation index Ki-67, which was significantly altered by NAT in all BC subtypes (p < 0.001 for HER2 positive and luminal A/B HER2 negative and p = 0.001 for TNBC). Multivariable analysis showed pre-NAT and post-NAT Ki-67 as independent predictors of survival outcomes for luminal A/B HER2 negative subtype. For TNBC, post-NAT Ki-67 was significant alone, and, for HER2 positive, the only borderline association of pre-NAT Ki-67 was observed in relation to the overall survival. Steroid and HER2 receptors were re-assessed just in a portion of the patients with aRCB. The concordance of both assessments was 92.9% for ER status, 80.1% for PR, and 92.2% for HER2. In conclusion, these real-world data of a consecutive cohort confirmed the importance of biomarkers assessment in patients with aRCB, and the need to consider specific BC subtypes when interpreting their influence on prognosis.

Does Residual Cancer Burden Predict Local Recurrence After Neoadjuvant Chemotherapy?

The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR). The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated. Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45;p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model. The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy.

Dynamic characterization of breast cancer response to neoadjuvant therapy using biophysical metrics of spatial proliferation

Current tools to assess breast cancer response to neoadjuvant chemotherapy cannot reliably predict disease eradication, which if possible, could allow early cessation of therapy. In this work, we assessed the ability of an image data-driven mathematical modeling approach for dynamic characterization of breast cancer response to neoadjuvant therapy. We retrospectively analyzed patients enrolled in the I-SPY 2 TRIAL at the Atrium Health Wake Forest Baptist Comprehensive Cancer Center. Patients enrolled on the study received four MR imaging examinations during neoadjuvant therapy with acquisitions at baseline (T0), 3-weeks/early-treatment (T1), 12-weeks/mid-treatment (T2), and completion of therapy prior to surgery (T3). We use a biophysical mathematical model of tumor growth to generate spatial estimates of tumor proliferation to characterize the dynamics of treatment response. Using histogram summary metrics to quantify estimated tumor proliferation maps, we found strong correlation of mathematical model-estimated tumor proliferation with residual cancer burden, with Pearson correlation coefficients ranging from 0.88 and 0.97 between T0 and T2, representing a significant improvement from conventional assessment methods of change in mean apparent diffusion coefficient and functional tumor volume. This data shows the significant promise of imaging-based biophysical mathematical modeling methods for dynamic characterization of patient-specific response to neoadjuvant therapy with correlation to residual disease outcomes.

Tratamiento neoadyuvante en el cáncer de mama. El papel del patólogo

Neoadjuvant treatment is a standard practice in patients with breast cancer that allows to perform more conservative surgeries, provides additional prognostic information and is very useful for evaluating the efficacy of drugs. Pathologists are of great importance in this context. The evaluation of the tumor in diagnostic biopsy is essential for a correct selection of patients who are candidates for neoadjuvant therapy. In order to standardize the management and pathological evaluation of breast and axillary specimens that have received treatment, a homogeneous definition of complete pathological response has been established and, in the case of residual disease, its quantification using the RCB system is recommended because it is objective, reproducible and clinically useful. The sampling of these specimens and the subsequent microscopic study should be able to provide the necessary data for the correct diagnosis of the complete pathological response and to be able to quantify the residual cancer burden (RCB).