Breast最新文献

Introduction

The financial impact of breast cancer has been discussed due to its high incidence and the increased costs of systemic therapy and is even more relevant in countries with low and medium socioeconomic development.

Objective

To evaluate the financial viability of using the MammaPrint™ (MP) genetic signature in a public and private system in a country with a medium socioeconomic development index.

Material and method

A pharmacoeconomic trial with a cost-benefit analysis evaluating the reduction in costs of chemotherapy, support drugs, and materials used during chemotherapy infusion in high-risk hormone receptor-positive (HR+) breast cancer patients submitted to analysis using the MammaPrint™ genetic signature.

Results

The value of using MammaPrint™ in the Unified Health System (SUS) would bring an additional cost of US$ 1,334.56 per patient in the over-50 age group. In private medicine, the use of MammaPrint™ in the same population would result in cost savings ranging from US$ 2,422.53 to US$ 9,989.95 per patient.

Conclusion

The use of MP in RH + breast cancer patients with high clinical risk and low genomic risk in Brazil leads to significant savings in resources when applied to supplementary healthcare. In the SUS, reducing the costs of MP for large-scale use could make its application viable. These values need to be re-evaluated in each institution, using the methodology applied in the trial, adjusting according to costs, to obtain a result that reflects its reality.

Introduction

Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors.

Methods

To refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy.

Results

A total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible.

Conclusion

The unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

Purpose

There are a wide variety of intraoperative techniques available in breast surgery to achieve low rates for positive margins of excision. The objective of this systematic review was to determine the pooled diagnostic accuracy of intraoperative breast margin assessment techniques that have been evaluated in clinical practice.

Methods

This study was performed in accordance with PRISMA guidelines. A systematic search of the literature was conducted to identify studies assessing the diagnostic accuracy of intraoperative margin assessment techniques. Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included in the meta-analysis. A bivariate model for diagnostic meta-analysis was used to determine overall pooled sensitivity and specificity.

Results

Sixty-one studies were eligible for inclusion in this systematic review and meta-analysis. Cytology demonstrated the best diagnostic accuracy, with pooled sensitivity of 0.92 (95 % CI 0.77–0.98) and a pooled specificity of 0.95 (95 % CI 0.90–0.97). The findings also indicate good diagnostic accuracy for optical spectroscopy, with a pooled sensitivity of 0.86 (95 % CI 0.76–0.93) and a pooled specificity of 0.92 (95 % CI 0.82–0.97).

Conclusion

Pooled data indicate that optical spectroscopy, cytology and frozen section have the greatest diagnostic accuracy of currently available intraoperative margin assessment techniques. However, long turnaround time for results and their resource intensive nature has prevented widespread adoption of these methods. The aim of emerging technologies is to compete with the diagnostic accuracy of these established techniques, while improving speed and usability.

Background

The aim of this population-based cohort study was to investigate the impact of neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy in prognosis among patients with HR+/HER2 negative breast cancer.

Method

This population-based study utilized data from the research database BCBaSe 3.0, based on the Swedish National Quality breast cancer register, including all patients with breast cancer diagnosis in Sweden between 2008 and 2019. Propensity score matching approach was applied. The outcomes of interest consisted of distant-disease free (DDFS), breast-cancer specific (BCSS), and overall survival (OS).

Results

In total, 14 459 patients were included in the study cohort of whom 2086 received NACT. After 1:1 propensity score matching (PSM), 1539 patients in each study group were available for analyses. No statistically significant difference in survival outcomes were observed between patients treated with NACT compared to those treated with adjuvant chemotherapy (Hazard Ratio (HR) for DDFS: 1.20; 95 % CI: 0.80–1.79; HR for BCSS: 1.16; 95 % CI: 0.54–2.49; HR for OS: 1.14; 95 % CI: 0.64–2.05).

Conclusion

In this population-based cohort study of patients with HR+/HER2-breast cancer, the use of NACT seems to be comparable to adjuvant chemotherapy in terms of prognosis, although non-inferiority cannot be proven by this study design. Until further evidence suggesting a survival benefit in favor of either treatment is available, NACT can be pursued when surgical-de-escalation is intended.

Background

To explore whether specific clinicopathological covariates are predictive for a benefit from capecitabine maintenance in early-stage triple-negative breast cancer (TNBC) in the SYSUCC-001 phase III clinical trial.

Methods

Candidate covariates included age, menstrual status, type of surgery, postoperative chemotherapy regimen, Ki-67 percentage, histologic grade, primary tumor size, lymphovascular invasion, node status, and capecitabine medication. Their nonlinear effects were modeled by restricted cubic spline. The primary endpoint was disease-free survival (DFS). A survival prediction model was constructed using Cox proportional hazards regression analysis.

Results

All 434 participants (306 in development cohort and 128 in validation cohort) were analyzed. The estimated 5-year DFS in development and validation cohorts were 77.8 % (95 % CI, 72.9%–82.7 %) and 78.2 % (95 % CI, 70.9%–85.5 %), respectively. Age and node status had significant nonlinear effects on DFS. The prediction model constructed using four covariates (node status, lymphovascular invasion, capecitabine maintenance, and age) demonstrated satisfactory calibration and fair discrimination ability, with C-index of 0.722 (95 % CI, 0.662–0.781) and 0.764 (95 % CI, 0.668–0.859) in development and validation cohorts, respectively. Moreover, patient classification was conducted according to their risk scores calculated using our model, in which, notable survival benefits were reported in low-risk subpopulations. An easy-to-use online calculator for predicting benefit of capecitabine maintenance was also designed.

Conclusions

The evidence-based prediction model can be readily assessed at baseline, which might help decision making in clinical practice and optimize patient stratification, especially for those with low-risk, capecitabine maintenance might be a potential strategy in the early-disease setting.

Introduction

Invasive lobular carcinoma (ILC) accounts for 5–15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile.

Methods

All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile.

Results

A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001).

A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001).

Conclusions

Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

Background

We assessed the potential role of serial circulating tumor DNA (ctDNA) as a biomarker to monitor treatment response to primary systemic therapy (PST) in breast cancer and evaluated the predictive value of ctDNA to further identify patients with residual disease.

Methods

We prospectively enrolled 208 plasma samples collected at three time points (before PST, after 2 cycles of treatment, before surgery) of 72 patients with stage Ⅱ-III breast cancer. Somatic mutations in plasma samples were identified using a customized 128-gene capture panel with next-generation sequencing. The correlation between early change in ctDNA levels and treatment response or long-term clinical outcomes was assessed.

Results

37 of 72 (51.4%) patients harbored detectable ctDNA alterations at baseline. Patients with complete response showed a larger decrease in ctDNA levels during PST. The median relative change of variant allele fraction (VAF) was −97.4%, −46.7%, and +21.1% for patients who subsequently had a complete response (n = 11), partial response (n = 11), and no response (n = 15) (p = 0.0012), respectively. In addition, the relative change of VAF between the pretreatment and first on-treatment blood draw exhibited the optimal predictive value to tumor response after PST (area under the curve, AUC = 0.7448, p = 0.02). More importantly, early change of ctDNA levels during treatment have significant prognostic value for patients with BC, there was a significant correlation between early decrease of VAF and longer recurrence-free survival compared to those with an VAF increase (HR = 12.54; 95% CI, 2.084 to 75.42, p = 0.0063).

Conclusion

Early changes of ctDNA are strongly correlated with therapeutic efficacy to PST and clinical outcomes in BC patients. The integration of preoperative ctDNA evaluation could help improving the perioperative management for BC patients receiving PST.

Purpose

Accurate identification of primary breast cancer and axillary positive-node response to neoadjuvant chemotherapy (NAC) is important for determining appropriate surgery strategies. We aimed to develop combining models based on breast multi-parametric magnetic resonance imaging and clinicopathologic characteristics for predicting therapeutic response of primary tumor and axillary positive-node prior to treatment.

Materials and methods

A total of 268 breast cancer patients who completed NAC and underwent surgery were enrolled. Radiomics features and clinicopathologic characteristics were analyzed through the analysis of variance and the least absolute shrinkage and selection operator algorithm. Finally, 24 and 28 optimal features were selected to construct machine learning models based on 6 algorithms for predicting each clinical outcome, respectively. The diagnostic performances of models were evaluated in the testing set by the area under the curve (AUC), sensitivity, specificity, and accuracy.

Results

Of the 268 patients, 94 (35.1 %) achieved breast cancer pathological complete response (bpCR) and of the 240 patients with clinical positive-node, 120 (50.0 %) achieved axillary lymph node pathological complete response (apCR). The multi-layer perception (MLP) algorithm yielded the best diagnostic performances in predicting apCR with an AUC of 0.825 (95 % CI, 0.764–0.886) and an accuracy of 77.1 %. And MLP also outperformed other models in predicting bpCR with an AUC of 0.852 (95 % CI, 0.798–0.906) and an accuracy of 81.3 %.

Conclusions

Our study established non-invasive combining models to predict the therapeutic response of primary breast cancer and axillary positive-node prior to NAC, which may help to modify preoperative treatment and determine post-NAC surgery strategy.

Purpose

The number of women living with breast cancer (BC) is increasing, and the efficacy of surveillance programs after BC treatment is essential. Identification of links between mammographic features and recurrence could help design follow up strategies, which may lead to earlier detection of recurrence. The aim of this study was to analyze associations between mammographic features at diagnosis and their potential association with recurrence-free survival (RFS).

Methods

Women with invasive BC in the prospective Malmö Diet and Cancer Study (n = 1116, 1991–2014) were assessed for locoregional and distant recurrences, with a median follow-up of 10.15 years. Of these, 34 women were excluded due to metastatic disease at diagnosis or missing recurrence data. Mammographic features (breast density [BI-RADS and clinical routine], tumor appearance, mode of detection) and tumor characteristics (tumor size, axillary lymph node involvement, histological grade) at diagnosis were registered. Associations were analyzed using Cox regression, yielding hazard ratios (HR) with 95 % confidence intervals (CI).

Results

Of the 1082 women, 265 (24.4 %) had recurrent disease. There was an association between high mammographic breast density at diagnosis and impaired RFS (adjusted HR 1.32 (0.98–1.79). In analyses limited to screen-detected BC, this association was stronger (adjusted HR 2.12 (1.35–3.32). There was no association between mammographic tumor appearance and recurrence.

Conclusion

RFS was impaired in women with high breast density compared to those with low density, especially among women with screen-detected BC. This study may lead to insights on mammographic features preceding BC recurrence, which could be used to tailor follow up strategies.

Purpose

This systematic review aims to explore the impact of age on physical functioning post-treatment for early-stage, locally advanced, or locally recurrent breast cancer, as measured by patient-reported outcome measures (PROMs), identify PROMs used and variations in physical functioning terms/labels.

Methods

MEDLINE, EmBase, PsycINFO, CINAHL and AMED were searched, along with relevant key journals and reference lists. Risk of bias (quality) assessment was conducted using a Critical Appraisal Skills Programme checklist. Data was synthesised through tables and narrative.

Results

28,207 titles were extracted from electronic databases, resulting in 44 studies with age sub-groups, and 120 without age sub-groups. Of those with findings on the impact of age, there was variability in the way findings were reported and 21 % found that age did not have a significant impact. However, 66 % of the studies found that with older age, physical functioning declined post-treatment. Comorbidities were associated with physical functioning declines. However, findings from sub-groups (breast cancer stage, treatment type and time post-treatment) lacked concordance. Twenty-eight types of PROM were used: the EORTC QLQ-C30 was most common (50.6 %), followed by the SF-36 (32.3 %). There were 145 terms/labels for physical functioning: ‘physical functioning/function’ was used most often (82.3 %).

Conclusions

Findings point towards an older age and comorbidities being associated with more physical functioning declines. However, it was not possible to determine if stage, treatment type and time since treatment had any influence. More consistent use of the terminology ‘physical functioning/function’ would aid future comparisons of study results.