Chemotherapy For Breast Cancer Research Articles

Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA

BackgroundTriple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).MethodsPatients with TNBC were enrolled between 2017–2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher’s exact tests were used for comparisons between groups and Kaplan–Meier analysis used for survival outcomes.ResultsIn total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively).ConclusionsEarly clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study.

Use qualitative and quantitative methods to explore factors influencing the adoption of guideline-based physical activity (PA) and dietary recommendations among participants enrolled in a lifestyle intervention during and after chemotherapy for breast cancer. Among women with stage I-III breast cancer who participated in the intervention arm of the Lifestyle, Exercise, and Nutrition early after diagnosis (LEANer) trial, we used stratified, purposeful sampling to interview women who met both, one, or neither intervention goal after the 1-year intervention: (1) 150min/week moderate-to-vigorous intensity exercise via a self-reported PA questionnaire and (2) improved self-reported diet quality measured by the Healthy Eating Index-2015. Semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed using thematic content analysis. The 29 women interviewed were 52 ± 11years old on average, with a mean body mass index of 29.6 ± 7.7kg/m2. Three themes emerged regarding aspects of the LEANer intervention that facilitated behavior change: (1) providing a conduit of trustworthy, timely, and personalized support and education; (2) shifting mindsets and enhanced understanding of the benefits of PA and nutrition during chemotherapy; and (3) fostering a sense of control and alternative focus. Factors described as hindering adoption of goals included: (1) adverse effects of chemotherapy and (2) competing priorities. Women reported the external support, tailored education, and experiencing the physical and mental benefits of the LEANer intervention facilitated the adoption of the interventions' behavioral goals. Addressing chemotherapy-related symptoms and competing priorities may facilitate adherence to lifestyle interventions during chemotherapy for breast cancer.

Utility of PET-CT for assessment of response to neo-adjuvant chemotherapy in breast cancer.

12 Background: Response to neo-adjuvant chemotherapy (NACT) is associated with prognosis in non-metastatic breast cancer and can potentially inform further therapeutic options. The aim of this study was to correlate post NACT response on PET CT with pathological response. Methods: All patients who underwent pre- NACT (baseline) and post NACT PET CT imaging with F-18 FDG in a dose of 5-7 MBq/kg body weight with a minimum of 185 MBq given intravenously were retrospectively analyzed. Scan was performed on GE Discovery 710 whole-body PET scan with 128 slice CT. Relevant clinical and imaging related details were extracted from the treatment records. Post NACT PET response (PERCIST criteria) in the primary tumor and nodes was correlated with the pathological response on the post surgical specimen. Analysis was done using Microsoft Excel and SPSS v20 (IBM SPSS). Results: The median age was 49 years (range 30-76 years). 83.1% of patients had node positive disease on baseline PET imaging (not pathologically confirmed). Post chemotherapy PET showed complete metabolic response in the primary tumor and regional nodes in 56.3% and 74% of patients respectively. Two patients had progressive local disease. Pathological complete response rates post surgery in triple negative, Her2 neu positive and ER positive group was 50%, 34% and 12% respectively. The sensitivity, specificity, positive predictive value and negative predictive value is tabulated below. Conclusions: Overall FDG PET CT showed good specificity with limited sensitivity for post NACT response assessment in breast cancer. Our results suggest that post NACT PET CT may have limited utility for clinical decision making and at present its use cannot be recommended outside of a clinical trial.[Table: see text]

THE EFECTIVENESS OF PROVIDING OREM SELF CARE BASED HEALTH EDUCATION ON IMPROVING THE QUALITY OF LIFE OF BREAST CANCER PATIENTS

Introduction: Breast cancer can cause many problems, both psychosocial and physical problems, which can reduce the patient's quality of life. Therefore, an intervention is needed that can improve their quality of life. This study aims to analyze the benefits of the intervention of implementing a self-care orem-based education system to improve the quality of life of breast cancer chemotherapy patients at Graha Amerta Surabaya. Method: This study used a pre-experimental design with a one-group pre-posttest design method on 60 breast cancer patients treated with chemotherapy who were taken using a consecutive sampling technique. The quality of life instrument was measured using the EORTC QLQ-C30 questionnaire. Data were analyzed using the Wilcoxon signed rank statistical test. Results: The results of the study showed that after being given the intervention to implement an educational system based on self-care orem, the results showed that the majority of 39 (65.0%) respondents had a quality of life in the good category and 21 (35.0%) respondents had a quality of life in the sufficient category. The results of the Wilcoxon statistical test analysis on the quality of life of breast cancer patients produced a significance value of 0.000. Conclusion: There is a significant effect of implementing an OREM self-care system education on improving the quality of life of breast cancer chemotherapy patients at Graha Amerta Surabaya. It is hoped that nurses can implement interventions to implement educational systems based on self-care orem for breast cancer patients in hospitals so that patient independence can increase so that the patient's quality of life can be optimal.

Change in Biomarker Profile After Neoadjuvant Chemotherapy is Prognostic and Common Among Patients with HER2+ Breast Cancer

BackgroundRates of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer have improved, especially among human epidermal growth factor 2-positive (HER2+) and triple-negative subtypes. The frequency and significance of biomarker profile change in residual disease are unclear. This study aimed to determine the rate of biomarker profile changes after NAC and the impact on clinical outcomes in a contemporary cohort.MethodsUpon institutional review board approval, the study identified 634 consecutive patients treated with NAC between 2010 and 2022 at two academic institutions. The study cohort was focused on patients with residual disease who underwent biomarker profile retesting. Biomarker profile change for each subtype was compared across groups using Fisher-Irwin tests. Cox Proportional Hazards Model and Kaplan-Meier plots were performed to evaluate the association of changed versus unchanged biomarker profile with event-free survival.ResultsBiomarker retesting was performed for 259 (61.4 %) of 422 patients with residual disease. Biomarker profile change occurred in 18.1 % overall and was significantly higher among those with pre-NAC HER2+ disease (32.7 %, 17/52) than among those with HER2–disease (14.5 %, 30/207) (p = 0.004). Conversion of pre-NAC biomarker profiles of HR+HER2– and HR+HER2+ to triple-negative breast cancer (TNBC) post-NAC may be associated with worse event-free survival, hazard ratios of 2.23 (95 % confidence interval [CI], 0.90–5.53; p = 0.08), trending toward significance, and 36.7 (95 % CI, 2.2–610.8; p = 0.01), respectively.ConclusionsThe results from one of the largest contemporary cohorts demonstrated that biomarker profile change in patients with residual disease after NAC was common. Furthermore, specific biomarker profile change in residual disease may have prognostic value. These findings strengthen the rationale for routine re-testing of biomarkers in residual disease after NAC.

A randomized controlled study of neoadjuvant metformin with chemotherapy in nondiabetic breast cancer women: The METNEO study.

Clinical data demonstrate that metformin exhibits antiproliferative, proapoptotic and antimetastatic actions. Here, correlative molecular studies were undertaken to determine the roles of transmembrane tumour necrosis factor-related apoptosis-inducing ligand death receptors (DRs) and CD133, a glycoprotein biomarker of breast cancer (BC) stem cells, in the advantageous action of metformin on pathological and clinical outcomes in BC patients on neoadjuvant chemotherapy. We randomly assigned 70 nondiabetic BC patients in a 1:1 ratio to either neoadjuvant AC-T chemotherapy (4cycles of adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by 12 cycles of weekly paclitaxel 80 mg/m2) or AC-T with adjunct metformin (850 mg twice/day). The expressions of DR4, DR5 and CD133 were quantified in excised tissue samples with residual tumour cells. The overall clinical response (odds ratio: 22.67 [2.77-185.18], P= .004), breast-conserving surgery (odds ratio: 3.67 [1.303-10.321], P= .014) and pathological complete response (β =2.49 ±1.13 [0.274-4.712], P= .028) rates were significantly improved in the metformin arm. Tissues obtained from the metformin arm had upregulated mRNA expression of DR4 (Mean delta cycle thresholds ± standard error of the mean: 2.68 ±0.25 vs. 4.87 ±0.53, P= .0003) and DR5 (0.21 ±0.25 vs. 4.29 ±0.95, P= .0004) compared to control arm. The enhanced DR expression negatively correlated with that of CD133 + BC stem cells, which was significantly reduced by metformin at both cytoplasmic/membranous (43.48 vs. 100.00%, P< .0001) and nuclear sites (4.35 vs. 95.00%, P< .0001). Metformin improves clinical and pathological responses to neoadjuvant AC-T chemotherapy in BC via prompting directionally opposite changes in DRs (increments) and CD133 + (decrements) expressions. This study was registered in ClinicalTrials.gov (registration number: NCT04170465, https://clinicaltrials.gov/ct2/show/NCT04170465).

Eight-year follow-up of patient-reported outcomes in patients with breast cancer participating in exercise studies during chemotherapy.

Numerous randomized controlled trials (RCTs) have shown beneficial exercise effects on fatigue, anxiety and depression and health-related quality of life (HRQoL) in breast cancer (BC) patients during and shortly after treatment. Here, we investigated the long-term effects of exercise during chemotherapy for BC on these outcomes. We invited participants of two highly comparable RCTs that investigated the effects of exercise (EX) (versus usual care (UC)) during chemotherapy in patients with non-metastatic BC (N = 357) to participate in an 8-year follow-up. In both trials, fatigue, anxiety and depression and HRQoL were assessed using the same questionnaires, at multiple timepoints. Linear mixed-effect models were used to compare study arms over time. In total, 156 participants (EX = 82; UC = 74) completed the follow-up questionnaires. EX reported comparable general (between-group difference 0.73, 95% confidence interval (- 0.35; 1.80), ES = 0.18) and physical fatigue (0.55 (- 0.55; 1.65), ES = 0.13), small but statistically significantly higher levels of anxiety (1.24 (0.47 to 2.00), ES = 0.39) and depression (1.10 (0.34; 1.85), ES = 0.38), significantly lower global HRQoL (- 5.99 (- 10.65; - 1.32), ES = 0.34) and comparable summary HRQoL (- 1.90 (- 4.70; 0.89), ES = 0.16) compared to UC. No long-term beneficial effects of exercise during chemotherapy on BC patients' fatigue, anxiety, depression or HRQoL were observed. The less favourable outcomes for mood and HRQoL that were observed 8years after participation in an exercise intervention may be explained by selective loss-to-follow-up. The results highlight the need to incorporate strategies that promote physical activity maintenance after participation in an exercise programme to also counteract long-term detrimental side effects of cancer treatment.

Evaluation of neoadjuvant chemotherapy for clinical T1 triple-negative breast cancer

The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan–Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26–1.89, p < 0.001). NAC offers no additional benefits in any age group or T, N subgroups. Our findings suggest that NAC does not provide additional benefit to patients with clinical T1 TNBC, even in the presence of lymph node metastasis, or T1c.

Accuracy of MRI Versus PET/CT in the Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer.

Background Breast-conserving surgeries have significantly advanced breast cancer treatment, offering favorable oncological outcomes, enhanced cosmetic results, reduced postoperative morbidity, and better psychological acceptance compared to mastectomy. The introduction of neoadjuvant therapy has expanded the applicability of breast conservation surgery to include locally advanced tumors. Tumor response to neoadjuvant chemotherapy is evaluated using imaging modalities such as breast ultrasound, breast magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). Accurate prediction of therapeutic response facilitates the planning of surgical and adjuvant treatments. This study aims to compare the diagnostic accuracy of MRI and PET/CT in predicting treatment response to neoadjuvant chemotherapy in breast cancer patients. Methods This retrospective study was conducted at a tertiary care center in Bahrain. A total of 138 patients with locally advanced breast cancer or human epidermal growth factor receptor-2 (HER2) positive, hormone receptor-negative cancers who underwent breast-conserving surgeries between June 2018 and December 2022 were included. The inclusion criteria focused on patients achieving a complete pathological responsefollowing neoadjuvant systemic therapy, ensuring a homogenous study population. Patients with hormone receptor-positive early breast cancers or metastatic tumors, ineligible for neoadjuvant chemotherapy, were excluded. Non-responders and partial responders were also excluded from the study. Statistical analysis was performed using IBM SPSS v26.0 (IBM Corp., Armonk, US). Response rates for the imaging modalities and histopathology results were assessed. Agreement between histology and imaging modalities was computed using kappa statistics. Diagnostic performance for predicting "no residual" disease was evaluated using the McNemar Test. All tests were two-tailed, with a p-value <0.05 considered statistically significant. Results The study included 138 patients, of whom 73 (52.9%) had an incomplete response or residual disease, while 65 (47.1%) had a complete response or no residual disease according to histology reports. There was slight agreement between post-neoadjuvant MRI and histology results (Cohen's kappa 0.172, p=0.010), while substantial agreement was observed between post-neoadjuvant PET/CT and histology results (Cohen's kappa 0.614, p=0.000). PET/CT demonstrated a higher sensitivity of 93.8% (p<0.001) and a specificity of 68.5%. Although MRI was more specific, the positive predictive value was comparable for both PET/CT and MRI. Conclusion PET/CT shows higher sensitivity and can serve as an early marker for predicting complete pathological response in post-neoadjuvant breast cancer patients. However, the prediction of residual disease is optimized by combining both MRI and PET/CT as diagnostic modalities.

Trajectories of Depressive Symptoms Among Patients Undergoing Chemotherapy for Breast, Gastrointestinal, Gynecological, or Lung Cancer.

Individuals who undergo chemotherapy for cancer are at elevated risk of developing depressive symptoms, yet substantial interindividual variation exists in trajectories of these symptoms. To examine interindividual variations in trajectories of depressive symptoms during 2 cycles of chemotherapy and to evaluate associations between demographic and clinical characteristics, symptom severity scores, psychological adjustment characteristics (eg, stress and coping), and initial levels and trajectories of depressive symptoms. Patients (n = 1323) diagnosed with breast, gynecologic, lung, or gastrointestinal cancer completed the Center for Epidemiological Studies-Depression Scale 6 times, over 2 cycles of chemotherapy. At enrollment, patients provided demographic information and completed a broad range of symptom, stress, and coping measures. Hierarchical linear modeling was used to identify characteristics associated with initial levels and trajectories of depressive symptoms. Interindividual differences in initial levels of depressive symptoms were associated with marital status, functional status, level of comorbidity, chemotherapy toxicity, sleep disturbance, morning fatigue, cognitive function, global and cancer-related stress, and coping characteristics (ie, sense of coherence, venting, behavioral disengagement, and self-blame). Interindividual differences in depression trajectories were associated with education, cancer type, chemotherapy toxicity, sleep disturbance, evening energy, evening fatigue, cognitive function, global and cancer-related stress, and self-blame. We present new findings concerning the trajectories and predictors of depressive symptoms during chemotherapy. Modifiable risk factors (eg, stress and coping) are important targets for intervening to address depressive symptoms in oncology patients.

Accumulation of CD56+ CD16- Natural Killer Cells in Response to Preoperative Chemotherapy for Breast Cancer.

The activation of the antitumor immune responses of T cells and natural killer (NK) cells is important to induce breast tumor shrinkage via preoperative chemotherapy. We evaluated how antitumor immune responses contribute to the effects of such therapy. Forty-three patients with stages I - IV breast cancer who underwent surgery between August 2018 and Jun 2023 after preoperative chemotherapy were enrolled. Peripheral natural killer (pNK) cell activity was assessed by 51Cr-release assay, and the counts and percentages of CD4+, CD8+, and NK cells and their subsets in peripheral blood were measured before and after chemotherapy by two-color flow cytometry. Associations of cell population changes with chemotherapy responses were analyzed. On univariate analysis, relative to grade (G) ≤ 1 effects, G ≥ 2 therapeutic effects were associated significantly with human epidermal growth factor receptor 2 (HER-2)+ breast cancer (P = 0.024) and post-chemotherapy CD56+ CD16- NK cell accumulation (8.4% vs. 5.5%, P = 0.042), and tended to be associated with increased pre-chemotherapy CD56+ CD16- NK cell percentages (5.4% vs. 3.3%, P = 0.054) and pNK cell activity (42.0% vs. 34.5%, P = 0.057). The accumulation and increased percentage of CD56+ CD16- NK cells in patients with G ≥ 2 effects were not associated with changes in pNK cell activity or the disappearance of axillary lymph-node metastases. On multivariate analysis, G ≥ 2 therapeutic effects tended to be associated with higher pre-chemotherapy pNK levels (odds ratio = 0.96; 95% confidence interval: 0.921 - 1.002; P = 0.067). The accumulation of the immunoregulatory CD56+ CD16- NK cell subset in the peripheral blood before and after chemotherapy may lead to the production of cytokines that induce an antitumor immune response. Activation of the immune response mediated by CD56+ CD16- pNK cells after chemotherapy and their high counts before chemotherapy may contribute to the improvement of therapeutic effects against breast cancer.

Neoadjuvant chemotherapy for breast cancer in Italy: A Senonetwork analysis of 37,215 patients treated from 2017 to 2022

BackgroundAdoption of neoadjuvant chemotherapy (NACT) in the “real world” has been poorly investigated. Aim of this study was to examine the rate of NACT in Italy, trends over time and determinants of therapeutic choices. MethodsSenonetwork, the recognized network of Breast Centers in Italy, has developed a voluntary national data warehouse with the aim to monitor and improve treatments quality. A retrospective analysis was conducted among 58,661 breast cancer (BC) patients treated between 2017 and 2022 by 24 high-volume Breast Centers participating in the project. ResultsAfter subset exclusion, 37,215 primary BC patients were analysed, 32,933 underwent primary-breast-surgery and 4,282 underwent NACT. From 2017 to 2022, the overall NACT incidence increased particularly for HR-/HER2+, Triple-Negative, and HR+/HER2+ BC (p < 0.001). In cN + patients the recommendation to axillary lymph-node dissection after NACT decreased over time along with an increase of <4 lymph-nodes removed (p < 0.001). Immediate breast reconstruction and indication for nipple sparing mastectomy increased significantly over time (OR = 1.10, p = 0.011 and OR 1.14, p < 0.001, respectively). On multivariate analysis, there was a trend towards an increased adoption of conservative treatment for HR-/HER2+ (p = 0.01) and Triple Negative tumors (p = 0.06). Implementation of NACT varied significantly among Breast-Centers from 3.8 to 17.7 % (p < 0.001). ConclusionThe impact of NACT on the subsequent surgical management is substantial and continues to evolve over time, resulting in less-extensive surgery. Even among high-volume Centers NACT implementation rate is still highly variable. Although we registered a significant increase in its use during the study period, these results need to be further improved.

The longitudinal changes in multiparametric MRI during neoadjuvant chemotherapy can predict treatment response early in patients with HER2-positive breast cancer

PurposeTo investigate whether longitudinal changes in multiparametric MRI can predict early response to neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) and to further establish quantitative models based on these features. MethodsA total of 164 HER2-positive BC patients from three centers were included. MRI was performed at baseline and after two cycles of NAC (early post-NAC). Clinicopathological characteristics were enrolled. MRI features were evaluated at baseline and early post-NAC, as well as longitudinal changes in multiparametric MRI, including changes in the largest diameter (LD) of the tumor (ΔLD), apparent diffusion coefficient (ADC) values (ΔADC), and time–signal intensity curve (TIC) (ΔTIC). The patients were divided into a training set (n = 95), an internal validation set (n = 31), and an independent external validation set (n = 38). Univariate and multivariate logistic regression analyses were used to identify the independent indicators of pCR, which were then used to establish the clinicopathologic model and combined model. The AUC was used to evaluate the predictive power of the different models and calibration curves were used to evaluate the consistency of the prediction of pCR in different models. Additionally, decision curve analysis (DCA) was employed to determine the clinical usefulness of the different models. ResultsTwo models were enrolled in this study, including the clinicopathologic model and the combined model. The LD at early post-NAC (OR=0.913, 95 % CI=0.953–0.994 p = 0.026), ΔADC (OR=1.005, 95 % CI=1.005–1.008, p = 0.007), and ΔTIC (OR=3.974, 95 % CI=1.276–12.358, p = 0.017) were identified as the best predictors of NAC response. The combined model constructed by the combination of LD at early post-NAC, ΔADC, and ΔTIC showed good predictive performance in the training set (AUC=0.87), internal validation set (AUC=0.78), and external validation set (AUC=0.79), which performed better than the clinicopathologic model in all sets. ConclusionsThe changes in multiparametric MRI can predict early treatment response for HER2-positive BC and may be helpful for individualized treatment planning.

Factors influencing pathological complete response and tumor regression in neoadjuvant radiotherapy and chemotherapy for high-risk breast cancer

BackgroundPathological complete response (pCR) is a well-established prognostic factor in breast cancer treated with neoadjuvant systemic therapy (naST). The determining factors of pCR are known to be intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage as well as type of systemic therapy. The addition of neoadjuvant radiotherapy (naRT) to this paradigm might improve response, freedom from disease, toxicity and cosmetic outcome compared to adjuvant radiotherapy. The factors for pCR and primary tumor regression when neoadjuvant radiation therapy is added to chemotherapy have not been thoroughly described.MethodsWe performed a retrospective analysis of 341 patients (cT1-cT4/cN0-N+) treated with naRT and naST between 1990 and 2003. Patients underwent naRT to the breast and mostly to the supra-/infraclavicular lymph nodes combined with an electron or brachytherapy boost. NaST was given either sequentially or simultaneously to naRT using different regimens. We used the univariate and multivariate regression analysis to estimate the effect of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) as well as complete primary tumor response (ypT0/Tis; bpCR) in our cohort. Receiver operating characteristic (ROC) analysis was performed to evaluate the interval between radiotherapy (RT) and resection (Rx) as well as radiotherapy dose.ResultsOut of 341 patients, pCR and pbCR were achieved in 31% and 39%, respectively. pCR rate was influenced by resection type, breast cancer subtype, primary tumor stage and interval from radiation to surgery in the multivariate analysis. Univariate analysis of bpCR showed age, resection type, breast cancer subtype, clinical tumor stage and grading as significant factors. Resection type, subtype and clinical tumor stage remained significant in multivariate analysis. Radiation dose to the tumor and interval from radiation to surgery were not significant factors for pCR. However, when treatment factors were added to the model, a longer interval from radiotherapy to resection was a significant predictor for pCR.ConclusionsThe factors associated with pCR following naST and naRT are similar to known factors after naST alone. Longer interval to surgery might to be associated with higher pCR rates. Dose escalation beyond 60 Gy did not result in higher response rates.

GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer

GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment. At median follow-up of 6.5 years (overall cohort) and 5.7 years (neoadjuvant cohort, N = 593), both regimens showed comparable 5-year OS rates (iddEnPC 90.8%, dtEC-dtD 90.0%, p = 0.320). In the neoadjuvant setting, iddEnPC yielded a higher pCR rate than dtEC-dtD (51.2% vs. 42.6%, p = 0.045). Patients achieving pCR had significantly improved 5-year iDFS (88.7% vs. 70.1%, HR 0.33, p < 0.001) and OS rates (93.9% vs. 83.1%, HR 0.32, p < 0.001), but OS outcomes were comparable regardless of pCR status. Thus, iddEnPC demonstrates superior pCR rates compared to dtEC-dtD, yet with comparable survival outcomes.

Axillary management and long-term oncologic outcomes in breast cancer patients with clinical N1 disease treated with neoadjuvant chemotherapy

BackgroundLow false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC.MethodsBC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014–2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed.Results81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70–11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84–35.60, p = 0.006).ConclusionsSLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone.

Altered ribosomal profile in acquired resistance and reversal associates with pathological response to chemotherapy in inflammatory breast cancer

Therapeutic resistance presents a significant hurdle in combating inflammatory breast cancer (IBC), adding to the complexity of its management. To investigate these mechanisms, we conducted a comprehensive analysis using transcriptomic and proteomic profiling in a preclinical model alone with correlates of treatment response in IBC patients. This included SUM149 cell lines derived from treatment-naïve patients, along with acquired drug resistance (rSUM149) and others in a state of resistance reversal (rrSUM149), aiming to uncover drug resistance networks. We identified specific ribosomal proteins associated with acquiring resistance. These correlated with elevated levels of molecular markers such as pERK, CDK1, XIAP, and SOD2. While resistance reversal in rrSUM149 cells largely normalized the expression profile, VIPER analysis revealed persistent alterations in ribosomal process-related proteins (AGO2, Exportin 1, RPL5), suggesting their continued involvement in drug resistance. Moreover, genes linked to ribosomal processes were significantly enriched (P < 0.001) among overexpressed genes in IBC patients (n = 87) who exhibited a pathological complete response (pCR) to neoadjuvant chemotherapy. Given the common hyperactivation of MAPK in IBC tumors, including rSUM149, we evaluated Merestinib, a multikinase inhibitor in clinical trials. It effectively targeted pERK and peIF4E pathways, suppressed downstream targets, induced cell death in drug-resistant rSUM149 cells, and showed synergistic effects with another tyrosine kinase inhibitor (Lapatinib) in parental cells. This underscores its significant impact on protein synthesis signaling, crucial for combating translational dependence in cancer cells. In summary, our study elucidates adaptive changes in IBC cells in response to therapy and treatment pauses, guiding precision medicine approaches for this challenging cancer type.

A Retrospective Analysis of the Association of Obesity with Anthracycline and Trastuzumab-Induced Cardiotoxicity in the Treatment of Breast Cancer and Lymphoma

IntroductionBackground: Trastuzumab and anthracyclines are mainstays of chemotherapy in breast cancer and lymphoma patients. We aimed to assess the relationship between obesity and the risk of developing chemotherapy-associated cardiotoxicity.Material and methodsA retrospective chart review was conducted of all patients who received trastuzumab or anthracyclines at our tertiary care center. Bivariate analyses were conducted to determine the association between demographic and clinical variables with cardiotoxicity status. Two multivariate logistic regression models were generated to assess whether BMI was independently associated with cardiotoxicity.ResultsOf the 368 patients receiving either trastuzumab or anthracyclines, 16 patients developed cardiotoxicity. Demographically, age, race, BMI, BSA, and weight did not differ between the patients who developed cardiotoxicity and those who did not. The mean dose of anthracycline and trastuzumab did not differ between the patients who developed cardiotoxicity and those who did not. Obesity was not found to increase the odds of developing cardiotoxicity and was slightly protective. A non-significant decrease in the odds of developing cardiotoxicity was found for every one-unit increase in BMI. In a multivariable model using BMI as a continuous predictor and controlling for BMI, age, hypertension, chemotherapy type and coronary artery disease, the only significant predictor of cardiotoxicity was a previous history of arrhythmia.ConclusionsObesity was not a significant risk factor for patients developing cardiotoxicity from trastuzumab or anthracycline based chemotherapy and may be a protective factor for cardiotoxicity. Additional studies with greater statistical power are needed to further evaluate this effect and independently evaluate obesity as a risk factor for cardiotoxicity.

A model combining BI-RADS® descriptors from pre-treatment B-mode breast ultrasound with clinicopathological tumor features shows promise in the prediction of residual disease after neoadjuvant chemotherapy

PurposeTo create a simple model using standard BI-RADS® descriptors from pre-treatment B-mode ultrasound (US) combined with clinicopathological tumor features, and to assess the potential of the model to predict the presence of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients. Method245 female BC patients receiving NAC between January 2017 and December 2019 were included in this retrospective study. Two breast imaging fellows independently evaluated representative B-mode tumor images from baseline US. Additional clinicopathological tumor features were retrieved. The dataset was split into 170 training and 83 validation cases. Logistic regression was used in the training set to identify independent predictors of residual disease post NAC and to create a model, whose performance was evaluated by ROC curve analysis in the validation set. The reference standard was postoperative histology to determine the absence (pathological complete response, pCR) or presence (non-pCR) of residual invasive tumor in the breast or axillary lymph nodes. Results100 patients (40.8%) achieved pCR. Logistic regression demonstrated that tumor size, microlobulated margin, spiculated margin, the presence of calcifications, the presence of edema, HER2-positive molecular subtype, and triple-negative molecular subtype were independent predictors of residual disease. A model using these parameters demonstrated an area under the ROC curve of 0.873 in the training and 0.720 in the validation set for the prediction of residual tumor post NAC. ConclusionsA simple model combining standard BI-RADS® descriptors from pre-treatment B-mode breast US with clinicopathological tumor features predicts the presence of residual disease after NAC.

Real-world data on adjuvant capecitabine after standard neoadjuvant chemotherapy for triple negative breast cancer.

Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with triple-negative breast cancer (TNBC) with tumors > 1 cm or positive axillary nodes. Pathologic complete response (pCR) has been used as an endpoint to select patients for treatment scaling. This study aimed to examine the benefit of adding adjuvant capecitabine for TNBC patients who did not achieve pCR after standard NACT in a real-world scenario. This retrospective cohort study included all patients with TNBC who underwent NACT between 2010 and 2020. Clinicopathological data were obtained from the patient records. Univariate and multivariate analyses were conducted at the 5 years follow-up period. We included 153 patients, more than half of whom had stage III (58.2%) and high-grade tumors (60.8%). The overall pCR rate was 34.6%, and 41% of the patients with residual disease received adjuvant capecitabine. Disease-specific survival (DSS) among the patients who achieved pCR was significantly higher (p<0.0001). Residual disease after NACT was associated with detrimental effects on DSS. In this cohort, we did not observe any survival benefit of adding adjuvant capecitabine for patients with TNBC subjected to NACT who did not achieve pCR (p=0.52). Our study failed to demonstrate a survival benefit of extended capecitabine therapy in patients with TNBC with residual disease after NACT. More studies are warranted to better understand the indication of systemic treatment escalation in this scenario.